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CHECKPOINT-INHIBITOR TOXICITY

Nervous system immune-related adverse events

Neurological irAEs are mostly non-specific grade 1-2 events, and high-grade ones run below 1% — but the phenotypes that do reach this atlas are among the most lethal in it. Myasthenia gravis carries roughly 20% fatality in the pharmacovigilance record, arrives earliest of the neurological events, and travels with myocarditis and myositis.

Symptoms overlap heavily here: weakness can be myasthenia gravis, myositis, or Guillain-Barré, and the first two also implicate the heart. SITC evaluates the triad with one shared work-up and refers every neurological irAE to a specialist regardless of severity — this atlas carries that rule rather than a grade threshold. Educational reference, not medical advice.

Anchored on the ASCO and SITC chapters for this organ. Every source is named beside the position it supports, and labeled with what kind of source it is.

At a glance

ICI-associated myasthenia gravis

Also called: ICI myasthenia gravis · myasthenic syndrome · MG · checkpoint inhibitor myasthenia

The earliest and deadliest of the neurological irAEs — median 29 days, roughly 20% fatality in the pharmacovigilance record — and the one that travels with myocarditis and myositis. Seronegative disease does not exclude it, and the threat to life is respiratory, so the pulmonary assessment is part of the diagnosis rather than a complication check.

Part of a syndrome that spans more than this organ — see Spans more than this organ below.

RareCriticalonset: weeks 1–6

Reported frequency

  • 0.47% of ICI reports vs. 0.04% of the full database (ROR 16.5, 95% CI 14.5-18.9) — Share of ICI adverse-event reports naming myasthenia gravis

    of 48,653 ICI reports · VigiBase spontaneous reports — a share of REPORTS and a disproportionality signal, not an incidence in treated patients

    pharmacovigilance · 31118078

  • 3.8% anti-CTLA-4, 6.1% anti-PD-1, 12.0% combination — Overall neurological adverse events across ICI trials (ALL neurological phenotypes, not this one)

    of 59 clinical trials totalling 9208 patients · Systematic review to February 2016. This is the ORGAN-level denominator, dominated by non-specific grade 1-2 events such as headache — it is carried here as context for how small a fraction myasthenia gravis is, never as this entity's rate

    narrative review · 28064139

Severity and class

  • below 1% — High-grade neurological adverse events (ALL neurological phenotypes)

    of 59 clinical trials totalling 9208 patients · Systematic review, all ICI classes. Organ-level, not specific to myasthenia gravis — no source cited here reports a grade ≥3 rate for this entity alone

    narrative review · 28064139

  • ~ 20% — Fatality among reported myasthenia gravis cases

    of Myasthenia gravis reports within 48,653 ICI adverse-event reports · VigiBase spontaneous reports. A fatality share among REPORTS, which over-represents severe outcomes — but note the direction of the contrast the study draws: the other neurological phenotypes sat at 6-12% in the same database

    pharmacovigilance · 31118078

  • Associated with anti-PD-1 — ICI class associated with myasthenia gravis reports

    of 48,653 ICI adverse-event reports against a full database of 18,518,994 · VigiBase disproportionality analysis to September 2018. A statement of association direction, not a ratio between classes — the study reports which class the phenotype tracked with, and this field carries that and nothing more

    pharmacovigilance · 31118078

Onset

Median 29 days — the earliest of the neurological phenotypes in the pharmacovigilance record, against 61-80 days for the others. The organ-level median across trials was 6 weeks, which is a different and slower population. Stored in the units each source printed; no median is converted to weeks.

Presentation

  • · Fatigable or fluctuating muscle weakness, proximal (neck and shoulder) more than distal
  • · Ptosis, double vision from extraocular movement abnormality, facial weakness, difficulty swallowing — bulbar and ocular muscles are commonly affected
  • · Diaphragmatic weakness with respiratory compromise, which is what makes this entity lethal
  • · Concurrent myocarditis or myositis — SITC calls the combination potentially dangerous, and the pharmacovigilance record found it frequent
  • · Seronegative presentation is common enough to matter: anti-AChR was positive in 66.7% (30/45) and anti-MuSK in 5.3% (1/19) of one 47-patient series, and SITC states toxicity can occur independent of positive serology

Differential

  • · Myositis — the reason SITC offers electrodiagnostic studies specifically to distinguish the two, and the reason finding one is not a reason to stop looking
  • · Myocarditis, which shares the triad and is carried as its own card in this atlas; troponin belongs in the work-up of weakness here, not only of chest symptoms
  • · Thyroid dysfunction, which SITC includes in the same evaluation
  • · Guillain-Barré syndrome and other polyneuropathies — ascending weakness with areflexia points there instead, and the treatment paths diverge
  • · Progression of the malignancy, including leptomeningeal or CNS disease

Work-up

  • Neurology consultation · All patients

    SITC attaches it to ANY grade of myasthenic symptoms, and refers every neurological irAE to a specialist regardless of severity. Not a grade threshold.

    34172516

  • Diagnostic antibody testing (anti-AChR, anti-MuSK) · All patients

    Confirms the diagnosis when positive. A negative panel does NOT exclude it — SITC states toxicity can occur independent of positive serology, and one series found anti-MuSK positive in 1 of 19.

    34172516

  • Pulmonary function with negative inspiratory force and vital capacity · All patients

    The measurement that detects diaphragmatic weakness before it becomes respiratory failure. SITC asks for it in the work-up and then for frequent repeat assessments during treatment.

    34172516

  • Evaluation for concurrent myositis, myocarditis and thyroid dysfunction · All patients

    The shared triad work-up. The pharmacovigilance record found concurrent myocarditis and myositis frequent in this phenotype specifically, and myocarditis is the member with 50% reported fatality.

    34172516, 31118078

  • Electrodiagnostic studies · If atypical

    Offered by SITC to distinguish myasthenia gravis from myositis, which present with overlapping weakness.

    34172516

Grade ladder

Grade 1
Hold the ICIConsider admission

Grade 1 — ASCO's cross-organ default continues an ICPi at grade 1 and names neurologic toxicity as one of its exceptions. SITC fills that exception without grading it: any grade of myasthenic symptoms gets a neurology consultation, and a diagnosis of myasthenia gravis discontinues the ICI. The dose on this rung is SITC's OCULAR myasthenia figure and applies only to ocular disease of grade ≤2.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. SITC gives the ocular grade ≤2 dose without a taper window; the window shown is ASCO's cross-organ 'at least 4-6 weeks', which is a FLOOR in its own text and is rendered here as an open-ended plan rather than a completion date.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy and pyridostigmine — A diagnosis of myasthenia gravis — not steroid failure. SITC names this the standard of care on diagnosis, alongside discontinuing the ICI.
  • · Neurology consultation at any grade of myasthenic symptoms
  • · Assess negative inspiratory force and vital capacity before treating this as mild
  • · Look for myocarditis and myositis — the triad is why an isolated-looking weakness is not isolated

Escalate when: Any bulbar symptom, any drop in negative inspiratory force or vital capacity, or any evidence of myocarditis or myositis. Weakness that is fatigable and progressing does not wait for a grade.

Grade 2
Hold — consider permanent discontinuationAdmit

Grade 2 — ASCO's general ladder may suspend the ICPi for most grade 2 toxicities. SITC's entity rule is stronger and ungraded: a diagnosis of myasthenia gravis discontinues ICI therapy and starts IVIG or PLEX with corticosteroids and pyridostigmine. The 0.5-1 mg/kg figure is carried here ONLY where the disease is ocular and grade ≤2; a generalized grade 2 myasthenia gravis is outside the scope of that sentence and no other dose is stated.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy and pyridostigmine — Diagnosis of myasthenia gravis, at any grade.
  • · Discontinue the ICI on diagnosis
  • · Frequent pulmonary assessments — SITC's word is frequent, and this is the organ that kills
  • · Evaluate concurrent myositis, myocarditis and thyroid dysfunction

Sources differ here

Rechallenge

  • ASCO 2021 (society guideline) — Hold ICPi and may resume in G2 patients (MGFA 1 and 2) only if symptoms resolve and steroid taper completed.
  • SITC 2021 (society guideline) — ICI therapy is discontinued on a diagnosis of myasthenia gravis, without a grade condition and without a stated route back.

Escalate when: Falling vital capacity or negative inspiratory force, dysphagia, or any cardiac finding. Respiratory compromise is the failure mode, not limb weakness.

Grade 3
Discontinue permanentlyAdmit

Grade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3 across organs. SITC's entity rule already discontinues the drug and starts IVIG or PLEX. The ocular grade ≤2 dose does NOT reach this rung, and SITC's high-dose pulse corticosteroid sentence for myasthenia gravis states no dose, so none is encoded.

Dose not carried

SITC's standard of care for autoimmune myasthenia gravis includes high-dose pulse corticosteroids, and that sentence names no dose, route or duration. The only myasthenia figure in the chapter is scoped to OCULAR disease at grade ≤2, which this rung is not. Importing the encephalitis or Guillain-Barré pulse regimen from two paragraphs away would be a cross-entity borrow of exactly the kind this atlas does not permit, so the rung states that the dose is not carried rather than supplying one.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy and pyridostigmine — Diagnosis of myasthenia gravis. SITC names IVIG and PLEX as the standard of care, not as a rescue.
  • · Permanent discontinuation of the ICI
  • · Frequent pulmonary assessments, with a threshold for ventilatory support set by neurology and critical care
  • · Rule in or out the myocarditis that travels with this phenotype before attributing everything to weakness

Escalate when: Respiratory failure, myasthenic crisis, or concurrent myocarditis.

Grade 4
Discontinue permanentlyICU

Grade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, with an endocrine exception that does not apply. SITC discontinues on diagnosis regardless of grade, so the two agree here.

Dose not carried

No dose for grade 4 myasthenia gravis is stated in any chapter held here. The ocular grade ≤2 figure does not extend, and no pulse dose is stated for this entity.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy and pyridostigmine — Diagnosis of myasthenia gravis.
  • · Critical care with airway and ventilatory management
  • · Permanent discontinuation of the ICI
  • · Continued evaluation for myocarditis and myositis — the triad does not resolve because the myasthenia is being treated

Escalate when: Already the top rung. Management of established myasthenic crisis is beyond what the chapters held here state.

Rechallenge

Rechallenge is contraindicated

The two chapters held here disagree, and the card keeps the stricter reading. SITC discontinues ICI therapy on a diagnosis of myasthenia gravis, without a grade condition and without describing a route back. ASCO does describe one, but only at grade 2 (MGFA classes I and II) and only once symptoms resolve AND the steroid taper is completed; at grades 3-4 it discontinues permanently. Against roughly 20% reported fatality, the earliest onset of any neurological phenotype and a frequent association with myocarditis, the stance stays contraindicated rather than individualized — but it is now the conservative reading of a DISAGREEMENT rather than of an absence, and both positions are set out under 'Sources differ here'. The empty recurrence field still says no source here reports what happens on resumption.

  • · ASCO states two, and only for grade 2 (MGFA classes I and II): symptoms must have resolved AND the steroid taper must be completed. SITC states none, because it does not describe a route back at all

Deliberately not carried

  • Where sources differ — No longer empty. SITC's recommendations and ASCO's Table 7 section 7.1 are both held, and on one decision they part: resumption. SITC discontinues on a diagnosis of myasthenia gravis without a grade condition; ASCO permits resumption at grade 2 (MGFA classes I and II) but only once symptoms resolve AND the steroid taper is completed. That is a genuine disagreement about the same decision at the same grade, so it is recorded as one below rather than resolved silently in either direction.
  • Reported frequency — Neither figure carried is an incidence in treated patients. The 0.47% is a share of spontaneous REPORTS with a disproportionality signal beside it; the 3.8/6.1/12.0% figures are the ORGAN-level trial rate across all neurological phenotypes, dominated by headache. Both framings say so in their population line. No source cited here reports how often ICI myasthenia gravis occurs per patient treated.
  • Grade 3 or higher share — The sub-1% high-grade figure carried is organ-level across all neurological phenotypes, and its population line says so. No source cited here reports a grade ≥3 rate for myasthenia gravis specifically. It is carried rather than left null because the organ-level ceiling is genuinely informative — high-grade neurological events are rare in aggregate — but it must not be read as this entity's severity rate.
  • Median time to onset — The phenotype-specific median is 29 days and the organ-level median is 6 weeks; they come from different sources and different populations. Converting 29 days to 4.14 weeks would print a number no source stated, and averaging the two would be worse. Both are in onset.note in their published units.
  • Corticosteroid dose, grades 3-4 — SITC states high-dose pulse corticosteroids for autoimmune myasthenia gravis and names no dose. The chapter's only myasthenia dose is scoped to OCULAR disease at grade ≤2 and is carried only on the rungs it covers. The 1000 mg IV methylprednisolone regimen in the same chapter is written for encephalitis and Guillain-Barré, and is not borrowed here — for a critical-tier entity this is the most consequential gap on the card and it is stated rather than filled.
  • Corticosteroid taper — No taper window, start trigger or step cadence is stated for myasthenia gravis anywhere in the chapter held here. The grade 1-2 rungs show ASCO's cross-organ 'at least 4-6 weeks' as an open-ended floor, sourced to ASCO and labeled as such on the taper line, and the step size and interval are empty together.
  • Serology test performance — The 66.7% and 5.3% positivity rates are stored as SITC states them, with their denominators (30/45 and 1/19), because the clinically load-bearing point is that a negative panel does not exclude the diagnosis. They are positivity rates in a 47-patient series, not sensitivity, and no negative predictive value is asserted.
  • Linked society recommendations — Left empty although ASCO and SITC are both in this atlas's guideline library: the recommendation stored against each of them there is scoped to ICI-related kidney injury, and linking them would put kidney dosing on a neurology card. The chapter is carried under Sources with its own quote.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: The presenting pattern of ICI myasthenia gravis and its bulbar, ocular and diaphragmatic involvement; that toxicity occurs independent of positive serology; the anti-PD-(L)1 skew; the myocarditis and myositis association; the standard of care (IVIG or PLEX with corticosteroids and pyridostigmine); the ICI discontinuation rule; the ocular grade ≤2 prednisone dose; and the work-up, including the pulmonary assessments and the electrodiagnostic study that separates myasthenia gravis from myositis.Supporting text: the full text
  • Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: ASCO's Table 7 section 7.1 myasthenia-gravis chapter, and only that entity: that ASCO defines NO grade 1 and warrants workup at all grades; the grade-2 hold with resumption permitted only once symptoms resolve AND the steroid taper is completed; prednisone 0.5 mg/kg orally daily at grade 2, weaned on improvement; pyridostigmine 30 mg three times daily titrated to 120 mg four times daily; and the grade 3-4 cell — the grade-2 recommendations continued plus permanent discontinuation, possible ICU-level monitoring, a taper beginning 3-4 weeks after initiation, IVIG 2 G/kg over 5 days or plasmapheresis, rituximab if refractory, and frequent pulmonary function assessment.Supporting text: the full text
  • Johnson DB, et al. (2019) Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.Cited for: Per-phenotype reporting shares and reporting odds ratios for myasthenia gravis, encephalitis, peripheral neuropathy and meningitis; the class split (myasthenia gravis and encephalitis with anti-PD-1, the others with anti-CTLA-4); and the fatality-and-onset contrast that separates myasthenia gravis from the rest — roughly 20% fatality at a median of 29 days, against 6-12% at 61-80 days, with frequent concurrent myocarditis and myositis.Supporting text: the PubMed abstract (checkable at the link above)
  • Cuzzubbo S, et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.Cited for: Overall neurological adverse-event incidence by ICI class across 59 trials, the observation that most events are grade 1-2 and non-specific, the sub-1% high-grade rate, the median 6-week onset, and that drug interruption plus steroids led to neurological recovery in most cases — including in Guillain-Barré syndrome, where steroids are not the usual recommendation.Supporting text: the PubMed abstract (checkable at the link above)

ICI-associated encephalitis

Also called: immune-related encephalitis · autoimmune encephalitis · encephalopathy · ICI encephalitis

Under 1% by SITC's estimate, and treated at full intensity from grade 1 — pulse-dose methylprednisolone plus IVIG or PLEX at any grade. Antibody panels are usually negative, so a normal autoimmune screen argues against nothing, and antivirals run empirically until viral encephalitis is excluded.

RareCriticalonset: weeks 6–12

Reported frequency

  • 0.51% of ICI reports vs. 0.05% of the full database (ROR 10.4, 95% CI 9.2-11.8) — Share of ICI adverse-event reports naming encephalitis

    of 48,653 ICI reports · VigiBase spontaneous reports — a share of REPORTS with a disproportionality signal, not an incidence in treated patients

    pharmacovigilance · 31118078

Severity and class

  • below 1% — High-grade neurological adverse events (ALL neurological phenotypes)

    of 59 clinical trials totalling 9208 patients · Systematic review, all ICI classes. Organ-level, not specific to encephalitis — no source cited here reports a grade ≥3 rate for this entity alone

    narrative review · 28064139

  • 6-12% — Fatality among reported neurological cases OTHER than myasthenia gravis

    of Encephalitis, peripheral neuropathy and meningitis reports within 48,653 ICI adverse-event reports · VigiBase spontaneous reports. The study gives this as a RANGE across the non-myasthenic phenotypes rather than a figure for encephalitis alone, and the framing is stored at that resolution rather than narrowed to one point

    pharmacovigilance · 31118078

  • Associated with anti-PD-1 — ICI class associated with encephalitis reports

    of 48,653 ICI adverse-event reports against a full database of 18,518,994 · VigiBase disproportionality analysis to September 2018. SITC states the same direction in prose — higher risk with anti-PD-(L)1 monotherapy or combination than with anti-CTLA-4 — and quantifies it no further

    pharmacovigilance · 31118078

Onset

The pharmacovigilance record groups encephalitis with the non-myasthenic neurological phenotypes at a median of 61-80 days — later than myasthenia gravis at 29 days. That is a range across several phenotypes, not a median for encephalitis alone. The organ-level median across trials was 6 weeks. No encephalitis-specific median is stated in any source cited here.

Presentation

  • · Altered behavior, confusion, agitation
  • · Short-term memory impairment
  • · Speech abnormality
  • · Seizures
  • · Positive autoimmune encephalitis or paraneoplastic antibodies are RARE — SITC's word — so a negative panel does not argue against the diagnosis

Differential

  • · Viral encephalitis, which is why SITC runs empirical antiviral treatment until it is ruled out rather than after
  • · Aseptic meningitis — SITC distinguishes them by mental status, which is typically normal in meningitis and not in encephalitis
  • · Hypophysitis, which SITC asks to be excluded in a patient presenting with headache
  • · CNS metastases and leptomeningeal disease
  • · Metabolic encephalopathy, sepsis, and drug effects — the ordinary causes of confusion in a patient with cancer

Work-up

  • MRI of the brain · All patients

    First item in SITC's encephalitis work-up, and what separates structural disease from an immune cause.

    34172516

  • Lumbar puncture with PCR for infectious encephalitis · All patients

    Infection is the diagnosis that must not be missed, and the reason antivirals start before results return rather than after.

    34172516

  • Autoimmune encephalopathy and paraneoplastic panels of blood and CSF · All patients

    Ordered by SITC, with the caveat SITC itself states: positive results are rare, so a negative panel does not exclude ICI encephalitis and must not delay treatment.

    34172516

  • Electroencephalogram · All patients

    Part of SITC's work-up; seizures are within the presenting range and may be non-convulsive.

    34172516

  • CBC, CMP and thyroid panel · All patients

    SITC's baseline set, covering the metabolic and endocrine causes of an altered mental state.

    34172516

  • Specialist referral · All patients

    SITC refers every neurological irAE to a specialist regardless of severity.

    34172516

Grade ladder

Grade 1
Hold the ICIAdmit

Grade 1 — ASCO's continue-at-grade-1 default names neurologic toxicity as an exception, and SITC supplies an explicitly ungraded regimen: patients with ANY grade of encephalitis receive pulse-dose methylprednisolone and additionally IVIG or PLEX. There is no low-intensity rung for this entity in the chapter held here.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. SITC gives the pulse regimen and no taper; the window shown is ASCO's cross-organ 'at least 4-6 weeks', which is a FLOOR in its own text and is rendered open-ended rather than as a completion date.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX) — Given WITH the pulse steroid at any grade — SITC's word is additionally, not instead.
  • IVIG 2 g/kg in divided doses over 5 days, PLEX one session every other day for 5–7 cycles, or rituximab 375 mg/m² weekly for 4 weeks — ICI-related encephalitis that does not respond to pulse-dose corticosteroids.
  • · Empirical antiviral treatment until viral encephalitis can be ruled out
  • · Exclude hypophysitis in a patient whose presentation includes headache
  • · Specialist referral regardless of severity

Escalate when: No response to pulse-dose corticosteroids, seizures, or a falling level of consciousness.

Grade 2
Hold — consider permanent discontinuationAdmit

Grade 2 — ASCO may suspend the ICPi for most grade 2 toxicities. SITC's encephalitis regimen does not change by grade: the same pulse-dose methylprednisolone with IVIG or PLEX.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX) — Given with the pulse steroid at any grade.
  • IVIG 2 g/kg in divided doses over 5 days, PLEX one session every other day for 5–7 cycles, or rituximab 375 mg/m² weekly for 4 weeks — No response to pulse-dose corticosteroids.
  • · Continue empirical antivirals until viral encephalitis is excluded
  • · EEG if the mental state fluctuates — non-convulsive seizures are within range
  • · Do not let a negative autoimmune panel delay treatment

Escalate when: Refractory disease, status epilepticus, or airway compromise from a falling conscious level.

Grade 3
Discontinue permanentlyICU

Grade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3; SITC has already done both at grade 1 for this entity. What changes at this rung is the care setting and the threshold for moving to the named refractory regimens.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG 2 g/kg in divided doses over 5 days, PLEX one session every other day for 5–7 cycles, or rituximab 375 mg/m² weekly for 4 weeks — No response to pulse-dose corticosteroids. These are the doses SITC states.
  • · Critical care with airway protection and seizure management
  • · Antivirals continue until infection is definitively excluded
  • · Neurology leads; the diagnosis is refined alongside treatment, not before it

Escalate when: Status epilepticus, cerebral edema, or continued deterioration on second-line therapy.

Grade 4
Discontinue permanentlyICU

Grade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, with an endocrine exception that does not apply here.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG 2 g/kg in divided doses over 5 days, PLEX one session every other day for 5–7 cycles, or rituximab 375 mg/m² weekly for 4 weeks — No response to pulse-dose corticosteroids.
  • · Critical care; permanent discontinuation of the ICI
  • · Infection excluded definitively before immunosuppression is escalated further

Escalate when: Already the top rung. Management of refractory ICI encephalitis beyond the named regimens is outside what the chapters held here state.

Rechallenge

Rechallenge is contraindicated

No source cited here describes resuming an ICI after encephalitis. SITC states no rechallenge position for this entity, and ASCO's grade 4 rule is permanent discontinuation. Given a phenotype treated at pulse-dose intensity from grade 1, the absence of a described route back is read conservatively rather than as an open question.

  • · None are stated by any source cited here

Deliberately not carried

  • Where sources differ — Empty although TWO chapters are now held for this entity. SITC's recommendations and ASCO's Table 7 section 7.6 are both read. Where they meet they point the same way — both treat from grade 1 and neither makes resumption conditional on a grade — so there is no rung-level position to set against the other.
  • Reported frequency — SITC estimates encephalitis at <1% and states no denominator, population or study behind that estimate, so it is not entered as a framing — a bare '<1%' with no denominator is exactly the shape this atlas declines to carry as a frequency. The figure carried instead is the pharmacovigilance reporting share, whose population line says what it is. The SITC estimate appears in the entry's oneLiner attributed to SITC as an estimate.
  • Mortality — The 6-12% carried is the pharmacovigilance study's range across ALL non-myasthenic neurological phenotypes — encephalitis, peripheral neuropathy and meningitis together. No encephalitis-specific fatality figure is stated in any source cited here, so the framing is stored at the resolution the source published rather than narrowed to a single number that would look phenotype-specific.
  • Onset — Same resolution problem: 61-80 days is a range across the non-myasthenic phenotypes, not an encephalitis median. No median is shown, and the note says which population the range describes.
  • Corticosteroid — No WEIGHT-BASED dose is carried, because none is stated. SITC gives this entity one corticosteroid instruction — pulse-dose methylprednisolone at 1000 mg IV daily for 3-5 days — and no mg/kg figure anywhere. Until this was corrected the rungs encoded 1-2 mg/kg/day, which rendered as the headline dose on every rung and appeared in no quote on this card: an invented figure sitting above a correctly sourced pulse regimen. The absolute dose SITC does state is now what the card shows.
  • Corticosteroid taper — SITC states the pulse regimen and the refractory regimens with their doses, and no taper window, start trigger or step cadence for encephalitis. Every rung shows ASCO's cross-organ 'at least 4-6 weeks' as an open-ended floor, labeled as ASCO's on the taper line, with the step size and interval empty together.
  • Care setting — No chapter held here states a care setting for encephalitis at any grade. The values are the atlas's reading for an entity SITC treats with pulse-dose steroids and IVIG or PLEX from grade 1 and works up with lumbar puncture and EEG, and each grade definition says the ladder's intensity is SITC's while the setting is not.
  • Linked society recommendations — Left empty although ASCO and SITC are both in this atlas's guideline library: the recommendation stored against each of them there is scoped to ICI-related kidney injury and would put kidney dosing on a neurology card.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: The estimated encephalitis incidence, its symptom range, the anti-PD-(L)1 and combination skew, the rarity of positive autoimmune or paraneoplastic antibodies, the full diagnostic work-up, the any-grade pulse-dose steroid with IVIG or PLEX, the named refractory regimens with their doses, and the empirical antiviral cover until viral encephalitis is excluded.Supporting text: the full text
  • Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: ASCO's Table 7 section 7.6 encephalitis chapter, and only that entity: its workup and its graded management, including the ICPi hold and the discussion of resumption weighing risks and benefits.Supporting text: the full text
  • Johnson DB, et al. (2019) Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.Cited for: Per-phenotype reporting shares and reporting odds ratios for myasthenia gravis, encephalitis, peripheral neuropathy and meningitis; the class split (myasthenia gravis and encephalitis with anti-PD-1, the others with anti-CTLA-4); and the fatality-and-onset contrast that separates myasthenia gravis from the rest — roughly 20% fatality at a median of 29 days, against 6-12% at 61-80 days, with frequent concurrent myocarditis and myositis.Supporting text: the PubMed abstract (checkable at the link above)
  • Cuzzubbo S, et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.Cited for: Overall neurological adverse-event incidence by ICI class across 59 trials, the observation that most events are grade 1-2 and non-specific, the sub-1% high-grade rate, the median 6-week onset, and that drug interruption plus steroids led to neurological recovery in most cases — including in Guillain-Barré syndrome, where steroids are not the usual recommendation.Supporting text: the PubMed abstract (checkable at the link above)

ICI-associated Guillain-Barré syndrome

Also called: GBS · ascending polyradiculoneuropathy · acute inflammatory demyelinating polyradiculoneuropathy · AIDP

The one entity in this atlas whose ICI recommendation carries the word always: SITC permanently discontinues the drug on diagnosis, at any grade. It arrives early — usually within the first 3 cycles — and unlike idiopathic Guillain-Barré, corticosteroids are given here alongside IVIG or PLEX.

Very rareCriticalonset: weeks 1–6

Severity and class

  • below 1% — High-grade neurological adverse events (ALL neurological phenotypes)

    of 59 clinical trials totalling 9208 patients · Systematic review, all ICI classes. Organ-level — no source cited here reports a rate for Guillain-Barré syndrome specifically at any grade

    narrative review · 28064139

  • More common with anti-CTLA-4 or anti-CTLA-4 plus anti-PD-1 than with anti-PD-(L)1 alone — ICI class associated with Guillain-Barré syndrome

    of Not stated — SITC gives the direction of the comparison and no numerator or denominator · SITC's chapter statement. Carried because the direction is opposite to myasthenia gravis and encephalitis, which is decision-relevant, but it is a qualitative comparison and the value says so

    guideline · 34172516

Onset

SITC states that Guillain-Barré syndrome can develop soon after ICI treatment is started, usually within the first 3 cycles. Cycles are not weeks — the interval depends on the agent and schedule — so no week bounds are entered and the bucket reflects 'early' without converting a cycle count into a duration. The organ-level median onset across trials was 6 weeks.

Presentation

  • · Early lower back or thigh pain, preceding the weakness
  • · Ascending weakness, sensory loss and areflexia — the main symptoms
  • · Facial weakness and impaired extraocular movement from cranial neuropathies
  • · Autonomic dysregulation
  • · Nerve root enhancement and thickening on imaging

Differential

  • · A compressive spinal lesion, which is why SITC's work-up opens with MRI of the spine rather than with nerve conduction studies
  • · Myasthenia gravis — fatigable weakness with bulbar and ocular signs rather than ascending weakness with areflexia, and a different treatment path
  • · Myositis, which shares limb weakness and is separated electrodiagnostically
  • · Non-Guillain-Barré polyneuropathies, which SITC manages differently and at a lower steroid dose — the distinction changes the regimen, so it is made before treating
  • · Malignant infiltration of nerve roots or the leptomeninges

Work-up

  • MRI of the spine · All patients

    First in SITC's work-up, explicitly to rule out a compressive lesion. Ordered before the diagnosis is treated as immune.

    34172516

  • Lumbar puncture · All patients

    Part of SITC's diagnostic set for suspected Guillain-Barré syndrome.

    34172516

  • EMG and nerve conduction studies · All patients

    Confirms the polyradiculoneuropathy and separates it from myositis and myasthenia gravis.

    34172516

  • Ganglioside antibody panel of blood and CSF · All patients

    SITC's serological component of the work-up.

    34172516

  • Frequent pulmonary assessments · All patients

    SITC asks for these specifically in Guillain-Barré syndrome. Ascending weakness reaches the diaphragm, and respiratory failure is the way this entity kills.

    34172516

  • Specialist referral · All patients

    SITC refers every neurological irAE to a specialist regardless of severity.

    34172516

Grade ladder

Grade 1
Discontinue permanentlyAdmit

Grade 1 — ASCO's continue-at-grade-1 default names neurologic toxicity as an exception, and SITC's rule here is the strongest in the atlas: patients diagnosed with Guillain-Barré syndrome should ALWAYS permanently discontinue ICI therapy. The steroid regimen is likewise ungraded — any grade receives pulse-dose methylprednisolone with IVIG or PLEX.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. SITC gives the pulse regimen and no taper; the window shown is ASCO's cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy — Diagnosis of Guillain-Barré syndrome — given with the steroid, not after it fails.
  • · Permanent discontinuation of the ICI — SITC's word is always, with no grade condition
  • · Frequent pulmonary assessments from the outset
  • · Exclude a compressive spinal lesion before treating the weakness as immune

Escalate when: Ascending weakness reaching respiratory muscles, bulbar involvement, or autonomic instability.

Grade 2
Discontinue permanentlyAdmit

Grade 2 — nothing in SITC's Guillain-Barré instruction is grade-conditioned. Same permanent discontinuation, same pulse-dose regimen, same IVIG or PLEX.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy — Diagnosis of Guillain-Barré syndrome, at any grade.
  • · Frequent pulmonary assessments — vital capacity trends decide the care setting
  • · Neurology leads management
  • · Autonomic monitoring; dysautonomia is part of the syndrome, not a complication of it

Escalate when: Falling vital capacity, bulbar weakness, or autonomic instability.

Grade 3
Discontinue permanentlyICU

Grade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3 across organs; SITC has already permanently discontinued the drug at grade 1 for this entity. The regimen does not change, the care setting does.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy — Diagnosis of Guillain-Barré syndrome.
  • · Critical care with ventilatory support available
  • · Continued autonomic monitoring
  • · Permanent discontinuation of the ICI

Escalate when: Respiratory failure or hemodynamic instability from dysautonomia.

Grade 4
Discontinue permanentlyICU

Grade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, which SITC's unconditional rule has already applied at every rung below.

Corticosteroid 1000 mg/day (intravenous, methylprednisolone pulse, daily for 3–5 days)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

Second line

  • IVIG or plasma exchange (PLEX), with corticosteroid therapy — Diagnosis of Guillain-Barré syndrome.
  • · Ventilatory support and critical care
  • · Permanent discontinuation of the ICI

Escalate when: Already the top rung. Management of established respiratory failure in Guillain-Barré syndrome is beyond what the chapters held here state.

Rechallenge

Rechallenge is contraindicated

Two chapters are held and they do not fully agree; the card keeps the stricter one. SITC says patients diagnosed with Guillain-Barré syndrome should ALWAYS permanently discontinue ICI therapy, with no grade condition and no exception. ASCO is not silent — its section 7.2 additional considerations advise 'extreme caution with rechallenging for severe cases after complete resolution of symptoms and tapered off immunosuppression', which is a narrow route back rather than none. That position is disclosed here rather than encoded: it is a caution, not a protocol, it names no grade, and for an entity that can take the airway this atlas does not convert a caution into a permission. No recurrence figure exists here.

  • · None are encoded. SITC's instruction is unconditional; ASCO's caution names complete resolution of symptoms and being tapered off immunosuppression, which are stated here but not made into a gated route

Deliberately not carried

  • Where sources differ — NOT empty of sources — see 'Sources differ here' is absent by choice. SITC's recommendations and ASCO's Table 7 section 7.2 are both held. They agree on treatment and differ only on rechallenge, where SITC discontinues unconditionally and ASCO permits extreme caution after complete resolution and taper off immunosuppression. That difference is carried in the rechallenge rationale rather than as a rung-level disagreement, because it is not attached to any grade.
  • Reported frequency — EMPTY. No source cited here reports a rate for ICI-associated Guillain-Barré syndrome. The pharmacovigilance study breaks out myasthenia gravis, encephalitis, peripheral neuropathy and meningitis, and does not report Guillain-Barré separately; the systematic review counts Guillain-Barré-like syndromes only among its 27 case reports, which is not a denominator. The list is empty rather than borrowing the peripheral-neuropathy share, which is a different phenotype with a different class association.
  • Mortality — Null. The 6-12% figure in the pharmacovigilance record covers encephalitis, peripheral neuropathy and meningitis, and Guillain-Barré is not among the phenotypes it breaks out. Nothing is carried rather than attributing another phenotype's fatality to this one.
  • Onset — SITC states 'usually within the first 3 cycles', which is not a duration — cycle length varies by agent and schedule, so converting it into weeks would manufacture a window. No median is shown and both range bounds are empty, and the note carries the cycle statement verbatim in substance.
  • Difference between ICI classes — The class comparison is carried, but it is qualitative — SITC states the direction and gives no numerator, denominator or ratio, and its basis is 'guideline' rather than a measured study. It is retained because the direction is opposite to myasthenia gravis and encephalitis and that difference is decision-relevant, and the value and denominator fields say plainly that no number was published.
  • Corticosteroid — No WEIGHT-BASED dose is carried, because none is stated. SITC gives this entity one corticosteroid instruction — pulse-dose methylprednisolone at 1000 mg IV daily for 3-5 days — and no mg/kg figure anywhere. Until this was corrected the rungs encoded 1-2 mg/kg/day, which rendered as the headline dose on every rung and appeared in no quote on this card: an invented figure sitting above a correctly sourced pulse regimen. The absolute dose SITC does state is now what the card shows.
  • Corticosteroid taper — SITC gives the pulse regimen and no taper for this entity. Every rung shows ASCO's cross-organ 'at least 4-6 weeks' as an open-ended floor labeled as ASCO's, with all three cadence fields null together.
  • Care setting — No care setting is stated for Guillain-Barré syndrome in the chapter held here. The values are the atlas's reading for an entity SITC treats with pulse steroids and IVIG or PLEX from grade 1 and monitors with frequent pulmonary assessments; each grade definition attributes the intensity to SITC and not the setting.
  • Linked society recommendations — Left empty although ASCO and SITC are both in this atlas's guideline library: the recommendation stored against each of them there is scoped to ICI-related kidney injury and would put kidney dosing on a neurology card.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: The anti-CTLA-4 and combination skew for Guillain-Barré syndrome, its timing within the first 3 cycles, the presenting sequence from lower back or thigh pain to ascending weakness and areflexia, the cranial and autonomic involvement, the imaging finding, the work-up including the compressive-lesion exclusion, the any-grade pulse-dose steroid with IVIG or PLEX, the unconditional permanent discontinuation, and the frequent pulmonary assessments.Supporting text: the full text
  • Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: ASCO's Table 7 section 7.2 Guillain-Barré chapter, and only that entity: that no grade 1 exists and all grades warrant intervention; that the management column is ONE MERGED CELL across G2 and G3-4, so grade 2 receives the same regimen — discontinue the ICPi, neurology consultation, admission with rapid ICU transfer available, IVIG 0.4 G/kg/d for 5 days (2 G/kg total) or plasmapheresis, and a reasonable trial of methylprednisolone 2-4 mg/kg/d in ICPi-related forms followed by a slow taper; that pulse dosing at 1 g daily for 5 days is scoped by its own sentence to G3-4; and ASCO's rechallenge position, which is extreme caution for severe cases after complete resolution and taper off immunosuppression.Supporting text: the full text
  • Cuzzubbo S, et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.Cited for: Overall neurological adverse-event incidence by ICI class across 59 trials, the observation that most events are grade 1-2 and non-specific, the sub-1% high-grade rate, the median 6-week onset, and that drug interruption plus steroids led to neurological recovery in most cases — including in Guillain-Barré syndrome, where steroids are not the usual recommendation.Supporting text: the PubMed abstract (checkable at the link above)

ICI-associated aseptic meningitis

Also called: immune-related meningitis · aseptic meningitis · ICI meningitis · meningeal irritation

Headache, neck stiffness and photophobia with a NORMAL mental status — that last feature is what separates it from encephalitis, and the two are managed at very different intensities. SITC gives 0.5–1 mg/kg/day of prednisone at any grade, and runs antibiotics until bacterial meningitis is excluded; hypophysitis and leptomeningeal metastasis are ruled out in the same pass, which is why the MRI covers the pituitary and the bloods include cortisol and ACTH.

RareSeriousonset: weeks 6–12

Reported frequency

  • 0.15% of ICI reports vs. 0.06% of the full database (ROR 3.1, 95% CI 2.5-3.9) — Share of ICI adverse-event reports naming meningitis

    of 48,653 ICI reports · VigiBase spontaneous reports — a share of REPORTS with a disproportionality signal, not an incidence in treated patients. It is the smallest of the four neurological shares the study breaks out, and the least disproportionate after peripheral neuropathy

    pharmacovigilance · 31118078

Severity and class

  • below 1% — High-grade neurological adverse events (ALL neurological phenotypes)

    of 59 clinical trials totalling 9208 patients · Systematic review, all ICI classes. Organ-level, not specific to meningitis — no source cited here reports a grade ≥3 rate for this entity alone

    narrative review · 28064139

  • 6-12% — Fatality among reported neurological cases OTHER than myasthenia gravis

    of Encephalitis, peripheral neuropathy and meningitis reports within 48,653 ICI adverse-event reports · VigiBase spontaneous reports. A RANGE across the three non-myasthenic phenotypes, not a figure for meningitis alone, and stored at that resolution rather than narrowed to a point estimate that would read as phenotype-specific

    pharmacovigilance · 31118078

  • Associated with anti-CTLA-4 — ICI class associated with meningitis reports

    of 48,653 ICI adverse-event reports against a full database of 18,518,994 · VigiBase disproportionality analysis to September 2018. The study makes this statement about the non-myasthenic neurological events as a GROUP rather than about meningitis alone; SITC states the same direction in prose for meningitis specifically — more frequent with anti-CTLA-4 and with anti-CTLA-4 plus anti-PD-(L)1 combinations than with anti-PD-(L)1 monotherapy — and quantifies it no further

    pharmacovigilance · 31118078

Onset

The pharmacovigilance record groups meningitis with the other non-myasthenic neurological phenotypes at a median of 61-80 days — later than myasthenia gravis at 29 days. That is a range across several phenotypes, not a median for meningitis alone. The organ-level median across trials was 6 weeks. No meningitis-specific median is stated in any source cited here.

Presentation

  • · Headache, neck stiffness and photophobia
  • · Low-grade fever and nausea
  • · Mental status TYPICALLY NORMAL — SITC's own contrast with encephalitis, and the finding that decides which of the two ladders applies

Differential

  • · Infectious meningitis — SITC asks for it to be seriously considered during diagnosis AND treatment, which is why antibiotics run before the cultures return rather than after
  • · Leptomeningeal metastasis, explicitly to be ruled out
  • · Hypophysitis, which SITC asks to be excluded in any patient presenting with headache — the reason the MRI covers the pituitary and the bloods include cortisol and ACTH
  • · Encephalitis, separated by mental status: normal here, altered there, and the treatment intensity differs by an order of magnitude
  • · The ordinary causes of headache in a patient with cancer — brain metastases, raised intracranial pressure, medication effect

Work-up

  • MRI of the brain and pituitary, with and without contrast · All patients

    SITC's first work-up item. The pituitary sequences are not incidental — they are how hypophysitis is excluded in a patient whose presenting symptom is headache.

    34172516

  • Lumbar puncture · All patients

    Separates aseptic from bacterial meningitis and is the test the empirical antibiotics are covering until it reports.

    34172516

  • Cortisol and ACTH · All patients

    Part of SITC's meningitis work-up, and the endocrine half of the hypophysitis exclusion.

    34172516

  • Specialist referral · All patients

    SITC refers every neurological irAE to a specialist regardless of severity.

    34172516

Grade ladder

Grade 1
Hold the ICIAdmit

Grade 1 — ASCO's continue-at-grade-1 default names neurologic toxicity as an exception, and SITC's dose for this entity is ungraded: aseptic meningitis of ANY grade receives 0.5–1 mg/kg/day of prednisone or equivalent, depending on severity. So there is no observation-only rung here, and the drug is held while the alternative diagnoses are excluded.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: ASCO states when: 'Steroids can be tapered after 2-4 weeks, monitoring for symptom recurrence.' It states no duration, so the window shown is its cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Antibiotics until bacterial meningitis can be ruled out — SITC's instruction, and it precedes the steroid decision rather than following it
  • · Exclude hypophysitis and leptomeningeal metastasis before the headache is treated as an irAE
  • · Specialist referral regardless of severity

Escalate when: Any change in mental status, which moves the patient onto the encephalitis pathway and its pulse-dose regimen, or a positive infectious work-up.

Grade 2
Hold the ICIAdmit

Grade 2 — ASCO may suspend the ICPi for most grade 2 toxicities. SITC's dose does not change by grade for this entity; the phrase that does the work is 'depending on severity', which moves the patient within the 0.5–1 mg/kg/day band rather than off it.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: ASCO states when: 'Steroids can be tapered after 2-4 weeks, monitoring for symptom recurrence.' It states no duration, so the window shown is its cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Continue antibiotics until bacterial meningitis is definitively excluded
  • · Neurology leads; the referral is not grade-conditioned
  • · Analgesia for the headache alongside the steroid

Escalate when: Altered mental status, seizures, or failure to improve on the sourced dose.

Grade 3
Hold — consider permanent discontinuationAdmit

Grade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3 across organs. SITC states no higher dose for meningitis at any grade, so the band shown is still SITC's; ASCO's higher-dose instruction is cross-organ and is not applied to this entity as though it were a meningitis dose.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: ASCO states when: 'Steroids can be tapered after 2-4 weeks, monitoring for symptom recurrence.' It states no duration, so the window shown is its cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Inpatient care with neurology input
  • · Re-examine the diagnosis if there is no response — a steroid-refractory meningitis is more likely to be infection or leptomeningeal disease than a refractory irAE

Escalate when: No response to corticosteroids, or any feature that reclassifies the presentation as encephalitis.

Grade 4
Discontinue permanentlyICU

Grade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, with an endocrine exception that does not apply here. SITC's dose statement remains ungraded.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: ASCO states when: 'Steroids can be tapered after 2-4 weeks, monitoring for symptom recurrence.' It states no duration, so the window shown is its cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Critical care; permanent discontinuation of the ICI
  • · Infection excluded definitively before immunosuppression is escalated

Escalate when: Already the top rung. A grade 4 neurological presentation with a normal mental status is unusual, and the sources held here state no meningitis-specific regimen beyond the dose band shown.

Rechallenge

Individualize the decision

ASCO states one and SITC does not. ASCO's section 7.5 holds the ICPi at every grade and says to discuss resumption with the patient only after taking the risks and benefits into account — a route back that is deliberative rather than gated on a threshold. SITC gives no discontinuation rule for this entity at all. The stance is individualized rather than contraindicated because this is the one neurological phenotype in this atlas that SITC treats at the LOW steroid band at every grade, and because nothing here describes it as irreversible. That is an absence of evidence, not evidence of safety, and the prerequisites say so.

  • · Complete resolution of symptoms off corticosteroids
  • · Infectious meningitis and leptomeningeal metastasis excluded rather than assumed, since a rechallenge decision made about the wrong diagnosis is the foreseeable harm here
  • · Hypophysitis excluded — a headache attributed to meningitis that is endocrine in origin will not be helped by any ICI decision
  • · Specialist involvement in the decision; SITC's referral instruction is not grade-conditioned and does not end at treatment

Deliberately not carried

  • Where sources differ — Empty although TWO chapters are now held for this entity. SITC's recommendations and ASCO's Table 7 section 7.5 are both read, and they complement rather than contradict: SITC gives the dose and no taper, ASCO gives the hold, a taper start at 2-4 weeks and no duration. Neither states a position the other contradicts at any rung, so there is nothing to set side by side.
  • Reported frequency — The only figure entered is the pharmacovigilance reporting share, whose population line says what it is. SITC's meningitis section states no incidence at all, and the systematic review does not break meningitis out from the neurological total — so there is no rate in treated patients to carry.
  • Mortality — The 6-12% carried is the pharmacovigilance study's range across ALL non-myasthenic neurological phenotypes together. No meningitis-specific fatality figure is stated in any source cited here.
  • Onset — Same resolution problem: 61-80 days is a range across the non-myasthenic phenotypes, not a meningitis median. No median is shown and both range bounds are empty, and the note says which population the range describes.
  • ICI action — SITC states no hold or discontinuation rule for aseptic meningitis at any grade; ASCO's section 7.5 does, and it is one merged instruction across all grades — hold the ICPi and discuss resumption with the patient only after weighing risks and benefits. The actions shown are now ASCO's own for this entity rather than its cross-organ ladder. Grade 3 remains 'hold, consider permanent' rather than permanent discontinuation because neither chapter discontinues for this phenotype below grade 4.
  • Second-line therapy — EMPTY at every rung. No source cited here names a second-line immunosuppressant for ICI aseptic meningitis. The rungs carry supportive measures and the sourced steroid band, and nothing is borrowed from the encephalitis card, whose IVIG, PLEX and rituximab doses are stated for a different entity.
  • Corticosteroid taper — SITC states the dose and no taper at all for meningitis. ASCO's section 7.5 states WHEN to start one — 'Steroids can be tapered after 2-4 weeks, monitoring for symptom recurrence' — but not how long it should run, so that sentence is carried as the taper's start trigger while the duration still falls back to ASCO's cross-organ 'at least 4-6 weeks', shown open-ended as the floor it is. The step size and interval stay empty: no chapter held here states a cadence.
  • Care setting — No chapter held here states a care setting for aseptic meningitis. The values follow from SITC's own instruction to give antibiotics until bacterial meningitis can be ruled out and to perform a lumbar puncture — care that is delivered inpatient — rather than from a stated setting, and each grade definition says which parts of the rung are sourced.
  • Linked society recommendations — Left empty although ASCO and SITC are both in this atlas's guideline library: the recommendation stored against each of them there is scoped to ICI-related kidney injury and would put kidney dosing on a neurology card.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: The presenting symptom set for ICI aseptic meningitis and the normal mental status that separates it from encephalitis; the three diagnoses to exclude (infectious meningitis, leptomeningeal metastasis, hypophysitis); the anti-CTLA-4 and combination skew; the ANY-GRADE 0.5–1 mg/kg/day prednisone dose; the work-up including the pituitary sequences and the cortisol and ACTH; and the antibiotics that run until bacterial meningitis is excluded.Supporting text: the full text
  • Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: ASCO's Table 7 section 7.5 aseptic-meningitis chapter, and only that entity: its workup and its graded management.Supporting text: the full text
  • Johnson DB, et al. (2019) Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.Cited for: Per-phenotype reporting shares and reporting odds ratios for myasthenia gravis, encephalitis, peripheral neuropathy and meningitis; the class split (myasthenia gravis and encephalitis with anti-PD-1, the others with anti-CTLA-4); and the fatality-and-onset contrast that separates myasthenia gravis from the rest — roughly 20% fatality at a median of 29 days, against 6-12% at 61-80 days, with frequent concurrent myocarditis and myositis.Supporting text: the PubMed abstract (checkable at the link above)
  • Cuzzubbo S, et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.Cited for: Overall neurological adverse-event incidence by ICI class across 59 trials, the observation that most events are grade 1-2 and non-specific, the sub-1% high-grade rate, the median 6-week onset, and that drug interruption plus steroids led to neurological recovery in most cases — including in Guillain-Barré syndrome, where steroids are not the usual recommendation.Supporting text: the PubMed abstract (checkable at the link above)

ICI-associated peripheral neuropathy (non-Guillain-Barré)

Also called: immune-related peripheral neuropathy · painful small-fiber sensory neuropathy · cranial mononeuropathy · non-Guillain-Barré polyneuropathy

The commonest neurological phenotype in the pharmacovigilance record and the one with the weakest disproportionality signal — chemotherapy, diabetes and B12 deficiency cause the same picture, which is why SITC's work-up is largely a metabolic and nutritional screen. Its steroid dose is scoped explicitly to GRADE ≤2: above that, this atlas carries no sourced dose rather than borrowing the Guillain-Barré regimen, which is a different entity with a different ladder.

UncommonRoutineonset: weeks 6–12

Reported frequency

  • 1.16% of ICI reports vs. 0.67% of the full database (IC025 0.68) — Share of ICI adverse-event reports naming peripheral neuropathy

    of 48,653 ICI reports · VigiBase spontaneous reports — a share of REPORTS, not an incidence in treated patients. The largest of the four neurological shares and the smallest gap to background: the study publishes NO reporting odds ratio for this phenotype, only the IC025, and none is entered here

    pharmacovigilance · 31118078

Severity and class

  • below 1% — High-grade neurological adverse events (ALL neurological phenotypes)

    of 59 clinical trials totalling 9208 patients · Systematic review, all ICI classes. Organ-level, not specific to peripheral neuropathy — no source cited here reports a grade ≥3 rate for this entity alone

    narrative review · 28064139

  • 6-12% — Fatality among reported neurological cases OTHER than myasthenia gravis

    of Encephalitis, peripheral neuropathy and meningitis reports within 48,653 ICI adverse-event reports · VigiBase spontaneous reports. A RANGE across the three non-myasthenic phenotypes, not a figure for peripheral neuropathy alone. Read with care on this card: the range is dominated by phenotypes that are managed at far higher intensity, and it is carried at the published resolution rather than narrowed

    pharmacovigilance · 31118078

  • Associated with anti-CTLA-4 — ICI class associated with peripheral neuropathy reports

    of 48,653 ICI adverse-event reports against a full database of 18,518,994 · VigiBase disproportionality analysis to September 2018. The study states this for the neurological events OTHER than myasthenia gravis and encephalitis as a group, which is the resolution at which it separates classes — it publishes no class breakdown for peripheral neuropathy alone

    pharmacovigilance · 31118078

Onset

The pharmacovigilance record groups peripheral neuropathy with the other non-myasthenic phenotypes at a median of 61-80 days. That is a range across several phenotypes, not a median for this one. The organ-level median across trials was 6 weeks, and SITC states that neurological irAEs typically occur within the first 3 months of starting an ICI.

Presentation

  • · Painful small-fiber sensory neuropathy
  • · Isolated cranial mononeuropathies, especially of the facial and abducens nerves
  • · Sensorimotor presentations — the phenotypes at this end of the range shade into Guillain-Barré syndrome, which is managed separately and far more aggressively
  • · Pain severe enough to require its own management, which SITC names

Differential

  • · Guillain-Barré syndrome — ascending weakness with areflexia, early back or thigh pain, and an autonomic component. The distinction changes the regimen from an oral steroid band to pulse-dose methylprednisolone with IVIG or PLEX and unconditional permanent discontinuation, so it is made before treating
  • · Chemotherapy-induced peripheral neuropathy, which is commoner than the immune cause in most patients receiving both
  • · Diabetic neuropathy — the reason SITC's screen includes hemoglobin A1c
  • · B12, B6 or folate deficiency, all in SITC's blood panel
  • · A paraproteinaemic neuropathy, which the serum protein electrophoresis is looking for
  • · A compressive or infiltrative spinal lesion, which the MRI of the spine excludes
  • · Myasthenia gravis or myositis when the weakness is proximal or fatigable rather than length-dependent

Work-up

  • MRI of the spine · All patients

    First in SITC's non-Guillain-Barré work-up, to exclude a compressive or infiltrative cause.

    34172516

  • EMG and nerve conduction studies · All patients

    Characterizes the neuropathy and separates a length-dependent axonal picture from the demyelinating polyradiculoneuropathy of Guillain-Barré syndrome.

    34172516

  • B12, B6, folic acid, hemoglobin A1c, serum protein electrophoresis, ESR and CRP · All patients

    SITC's blood panel. It is mostly a screen for the non-immune causes of the same presentation — deficiency, diabetes, paraproteinemia — which is the point: this phenotype is the one most likely to have an explanation other than the ICI.

    34172516

  • MRI of the brain · If atypical

    Added by SITC when ocular or bulbar symptoms are present.

    34172516

  • Specialist referral · All patients

    SITC refers every neurological irAE to a specialist regardless of severity.

    34172516

Grade ladder

Grade 1
Hold the ICIOutpatient

Grade 1 — SITC's dose sentence covers non-Guillain-Barré polyneuropathy of grade ≤2, so it applies here: 0.5–1 mg/kg/day of prednisone or equivalent, depending on severity. ASCO's continue-at-grade-1 default names neurologic toxicity as an exception, and the referral is not grade-conditioned.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. SITC gives the dose and no taper; the window shown is ASCO's cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Neuropathic pain medication — gabapentin, pregabalin or duloxetine — until the neuropathy resolves. SITC names the agents and the endpoint
  • · Screen for the non-immune causes before attributing the neuropathy to the ICI
  • · Specialist referral regardless of severity

Escalate when: Ascending or proximal weakness, areflexia, or autonomic features — all of which point at Guillain-Barré syndrome and its separate ladder.

Grade 2
Hold the ICIOutpatient

Grade 2 — the upper bound of SITC's dose statement for this entity, and the rung where 'depending on severity' means the top of the 0.5–1 mg/kg/day band. ASCO may suspend the ICPi for most grade 2 toxicities.

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity; the floor is ASCO's cross-organ minimum taper length.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Continue neuropathic pain management alongside the steroid
  • · Re-examine the diagnosis if weakness rather than sensory disturbance is progressing
  • · Neurology leads

Escalate when: Progression to grade 3, motor involvement, or any respiratory or bulbar symptom.

Grade 3
Discontinue permanentlyConsider admission

Grade 3 — above the scope of SITC's dose sentence, which stops at grade ≤2 for this entity, but WITHIN ASCO's. ASCO's peripheral-neuropathy chapter states a grade 3-4 regimen for this entity in its own row: permanently discontinue the ICPi, admit, neurology consultation, and IV methylprednisolone 2-4 mg/kg/d proceeding as per Guillain-Barré management. That chapter is now held, and the rung carries its dose and its ICI action rather than ASCO's cross-organ default.

Corticosteroid 2–4 mg/kg/day (intravenous)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. ASCO gives the grade 3-4 dose and routes onward to Guillain-Barré management without a taper window of its own; the window shown is its cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Reconsider Guillain-Barré syndrome explicitly — a severe, progressing neuropathy is the presentation most likely to have been classified as the wrong entity, and that entity has a stated regimen
  • · Continue neuropathic pain management
  • · Inpatient assessment if weakness is progressing or bulbar symptoms appear

Escalate when: Respiratory or bulbar involvement, ascending weakness, or areflexia — the point at which the Guillain-Barré card, not this one, states the management.

Grade 4
Discontinue permanentlyAdmit

Grade 4 — ASCO writes grades 3 and 4 as ONE row for this entity, so the regimen is the grade 3 regimen: permanent discontinuation, admission, neurology consultation, and IV methylprednisolone 2-4 mg/kg/d proceeding as per Guillain-Barré management. ASCO's own instruction is to move onto the Guillain-Barré algorithm at this severity rather than to escalate the dose further on this card.

Corticosteroid 2–4 mg/kg/day (intravenous)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. ASCO gives the grade 3-4 dose and routes onward to Guillain-Barré management without a taper window of its own; the window shown is its cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.

No step size or interval is carried: the chapter cited does not specify a taper cadence, and one is not invented here.

  • · Permanent discontinuation of the ICI, per ASCO's grade 4 rule
  • · Neurology-led inpatient care with pulmonary assessment if weakness involves respiratory muscles

Escalate when: Already the top rung. Management of a grade 4 neuropathy is not stated for this entity in any chapter held here.

Rechallenge

Individualize the decision

No source cited here states a rechallenge position for non-Guillain-Barré peripheral neuropathy. SITC gives no discontinuation rule for it and describes neuropathic pain treatment continuing 'until neuropathy resolves', which contemplates a course that ends; ASCO's rule is the cross-organ grade-4 one. The stance is individualized on that basis, and turns on whether the diagnosis was ever the immune one — a chemotherapy or deficiency neuropathy misattributed to the ICI makes both the stop and the restart decision on the wrong premise.

  • · Guillain-Barré syndrome excluded, since that diagnosis carries an unconditional permanent-discontinuation rule
  • · Resolution or near-resolution of symptoms, which is the endpoint SITC's own pain-management instruction names
  • · The non-immune causes reviewed again — B12, A1c and paraprotein results reconciled with the clinical course
  • · Specialist involvement in the decision

Deliberately not carried

  • Where sources differ — Empty although TWO chapters are now held for this entity. SITC's recommendations and ASCO's Table 7 section 7.3 are both read. They differ in reach rather than direction: SITC scopes its dose to grade ≤2 and ASCO states a grade 3-4 regimen, so the two complete each other across the ladder rather than competing at any one rung.
  • Reported frequency — The reporting share is carried WITHOUT a reporting odds ratio, because the study publishes none for this phenotype — it reports the two shares and the IC025 only. The other three neurological phenotypes in the same sentence do carry an ROR, and inferring one here from the shares would be a computed number presented as a published one.
  • Mortality — The 6-12% carried is the pharmacovigilance study's range across ALL non-myasthenic neurological phenotypes together. No figure specific to peripheral neuropathy exists in any source cited here, and the population line says so on a card where the range is most likely to mislead.
  • Onset — 61-80 days is a range across the non-myasthenic phenotypes, not a median for this one. No median is shown and both range bounds are empty.
  • Corticosteroid — No longer a gap. SITC's 0.5–1 mg/kg/day sentence is scoped to non-Guillain-Barré polyneuropathy of grade ≤2, and above that ASCO's own section 7.3 states IV methylprednisolone 2-4 mg/kg/d for THIS entity, in its own grade 3-4 row, with permanent discontinuation. Both rungs now carry that dose. Nothing is borrowed from the Guillain-Barré ladder, which remains a separate entry with a different regimen.
  • ICI action — SITC states no hold or discontinuation rule for this entity; ASCO's section 7.3 does, per rung — hold at grade 1, hold with resumption at ≤ G1 at grade 2, and permanent discontinuation across grades 3-4 — and each grade definition attributes the action to it.
  • Second-line therapy — EMPTY at every rung. No source cited here names a second-line immunosuppressant for non-Guillain-Barré peripheral neuropathy. The neuropathic pain agents SITC names are symptomatic treatment and are carried as supportive measures, not as second-line immunosuppression.
  • Corticosteroid taper — SITC states no taper for this entity. The two rungs with a sourced dose show ASCO's cross-organ 'at least 4-6 weeks' as an open-ended floor with all three cadence fields null together; the two unsourced rungs carry no taper at all.
  • Care setting — No chapter held here states a care setting. The values are the atlas's reading for a phenotype SITC manages with an oral steroid band and outpatient pain medication at grade ≤2, escalating only as weakness appears.
  • Linked society recommendations — Left empty although ASCO and SITC are both in this atlas's guideline library: the recommendation stored against each of them there is scoped to ICI-related kidney injury and would put kidney dosing on a neurology card.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: The phenotypic range of non-Guillain-Barré peripheral neuropathy — painful small-fiber sensory type, isolated cranial mononeuropathies of the facial and abducens nerves — that pain management may be required, the work-up including the metabolic and nutritional bloods, the named neuropathic pain agents given until the neuropathy resolves, and the steroid dose SITC scopes explicitly to GRADE ≤2 polyneuropathy.Supporting text: the full text
  • Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: ASCO's Table 7 section 7.3 peripheral-neuropathy chapter, and only that entity: the grade-1 low threshold to hold with a week of symptom monitoring; the grade-2 hold with resumption once back to ≤ G1, initial observation OR prednisone 0.5-1 mg/kg/d if progressing from mild, and gabapentin, pregabalin or duloxetine for pain; and the grade 3-4 cell — permanent discontinuation, admission, neurology consultation, and IV methylprednisolone 2-4 mg/kg/d proceeding as per GBS management.Supporting text: the full text
  • Johnson DB, et al. (2019) Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.Cited for: Per-phenotype reporting shares and reporting odds ratios for myasthenia gravis, encephalitis, peripheral neuropathy and meningitis; the class split (myasthenia gravis and encephalitis with anti-PD-1, the others with anti-CTLA-4); and the fatality-and-onset contrast that separates myasthenia gravis from the rest — roughly 20% fatality at a median of 29 days, against 6-12% at 61-80 days, with frequent concurrent myocarditis and myositis.Supporting text: the PubMed abstract (checkable at the link above)
  • Cuzzubbo S, et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.Cited for: Overall neurological adverse-event incidence by ICI class across 59 trials, the observation that most events are grade 1-2 and non-specific, the sub-1% high-grade rate, the median 6-week onset, and that drug interruption plus steroids led to neurological recovery in most cases — including in Guillain-Barré syndrome, where steroids are not the usual recommendation.Supporting text: the PubMed abstract (checkable at the link above)

Spans more than this organ

Triple-M overlap (myositis / myocarditis / myasthenia gravis)

triple M · myositis-myocarditis-myasthenia overlap · overlap syndrome · IM3

When to suspect it

  • Weakness with a raised CK that also carries a troponin rise, a new arrhythmia, ptosis, diplopia or dysphagia — any second organ turns a single-organ toxicity into this syndrome
  • SITC names the three together specifically because their symptoms overlap: limb and bulbar weakness can belong to any of them, and the first-diagnosed is not necessarily the whole picture
  • The pharmacovigilance record found myasthenia gravis distinguished from other neurological events by frequent CONCURRENT myocarditis and myositis — the co-occurrence is measured, not merely plausible
  • 9% of ICI-associated myositis carries myocarditis and 9% carries myasthenia gravis (SITC) — the figures are on the myositis card

Screen for the other members

  • Troponin and EKG · All patients — The myocarditis screen, and the finding that most changes management — myocardial involvement makes ICI discontinuation permanent and carries the syndrome's highest fatality.34172516
  • Creatine kinase · All patients — The myositis marker, with SITC's caveat that it misleads in both directions — asymptomatic with a raised CK, symptomatic with a normal one.34172516
  • Acetylcholine-receptor and MuSK antibodies, with electrodiagnostic studies · All patients — The myasthenia component. Serology can be negative — SITC states toxicity occurs independent of it — and electrodiagnostics separate myasthenia gravis from myositis.34172516
  • Negative inspiratory force and vital capacity · All patients — Both myasthenia gravis and myositis can weaken the diaphragm; respiratory failure is a shared route to death and is not visible on limb strength.34172516

How management changes

Manage to the most dangerous member, not the presenting one. If myocardial involvement is confirmed, the ICI is permanently discontinued (the myositis card's rule) rather than held, and management follows the myocarditis card — coronary care, pulse-dose methylprednisolone, second-line immunosuppression on the 24-hour non-response rule, and caution against infliximab. Myasthenic respiratory compromise is managed with IVIG or PLEX. No source cited here states a combined regimen for the syndrome as a unit; the deviation is to escalate to whichever member's ladder is highest, and each member card carries its own doses.

Rechallenge

Rechallenge is contraindicated — Any myocardial involvement makes discontinuation permanent on the myositis card, and both myasthenia gravis and Guillain-Barré carry contraindicated or discontinue-on-diagnosis stances of their own. The syndrome inherits the most conservative member's position — there is no configuration of the triad that reopens rechallenge, and no source cited here describes resuming an ICI after it.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: Myositis frequency by ICI class, its association with myocarditis and myasthenia gravis at 9% each, the mechanisms of fatality, the symptom range including the asymptomatic-with-raised-CK and symptomatic-with-normal-CK presentations, the 5-year sequelae figure, and the whole graded ladder — the rheumatology or neurology referral, the rule that grade 1 with raised CK and weakness is managed as grade 2, the grade 3 prednisone dose, the IV methylprednisolone and plasmapheresis or IVIG escalation, the hold-until-grade-1 rule with permanent discontinuation on myocardial involvement, the 4-6 week non-response trigger for steroid-sparing agents, and the rituximab caution.Supporting text: the full text
  • Johnson DB, et al. (2019) Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.Cited for: That myasthenia gravis was distinguished from the other neurological phenotypes by frequent CONCURRENT myocarditis and myositis, alongside its early onset and roughly 20% fatality — the pharmacovigilance evidence that this triad co-occurs rather than being three independent toxicities that happen to share symptoms.Supporting text: the PubMed abstract (checkable at the link above)

Other members: ICI-associated myositis, ICI-associated myocarditis

Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.

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