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CHECKPOINT-INHIBITOR TOXICITY

Blood immune-related adverse events

Rare — under 1% across a 745-patient registry — and high-grade in most REPORTED cases: 25 of 35 (71%) reached grade 4. That 35-patient cohort was assembled from grade-2-or-worse cases, so its denominator excludes grade 1 by construction and the share is not the severity rate of hematologic irAEs in general. The three commonest presentations are neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia, each managed as its hematological standard of care with a steroid backbone.

In a patient on chemo-immunotherapy a cytopenia is not automatically immune — SITC asks first to separate an immune cytopenia from chemotherapy myelosuppression, because the treatments diverge. Rechallenge is not free either: 43% of a small re-exposed group had a recurrence. 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 immune thrombocytopenia

Also called: ITP · immune thrombocytopenia · immune-related thrombocytopenia · checkpoint inhibitor thrombocytopenia

One of the three commonest hematological irAEs, and the one most easily mistaken for something else — a low platelet count in a patient with cancer has many non-immune causes, so a baseline count and the exclusion of DIC come before the diagnosis. Median onset 41 days; managed as standard-of-care ITP with a steroid backbone.

RareSeriousonset: weeks 1–6

Reported frequency

  • <1% — Overall hematological irAE frequency (ALL phenotypes, not ITP alone)

    of 745 anti-PD-(L)1-treated patients in the prospective REISAMIC registry · Organ-level figure for all haem-irAEs, carried on this anchor card. No ITP-specific incidence is stated in any source held here

    guideline · 34172516

Onset

SITC states a median time to onset for ITP of 41 days and a median time to resolve below grade 2 of 4 weeks. Stored in the units the source printed; 41 days is not converted to a weeks median.

Presentation

  • · A fall in platelet count, often against a baseline established before ICI therapy
  • · Bleeding or bruising in severe disease
  • · Frequently asymptomatic and found on routine counts

Differential

  • · Chemotherapy myelosuppression and other marrow-suppressing drugs
  • · Disseminated intravascular coagulation — SITC puts DIC labs (PT/PTT/fibrinogen/d-dimer) in the work-up to exclude it
  • · Cancer itself, radiation, infection, and pre-existing autoimmunity, which SITC lists as competing causes of thrombocytopenia in this population
  • · Pseudothrombocytopenia, excluded on the blood smear

Work-up

  • CBC with differential, against a baseline platelet count · All patients

    SITC advises a baseline count before ICI therapy so a later drop can be measured rather than guessed. The differential separates an isolated thrombocytopenia from a broader cytopenia.

    34172516

  • Blood smear evaluation · All patients

    Confirms true thrombocytopenia and excludes pseudothrombocytopenia and a microangiopathic picture.

    34172516

  • DIC labs — PT, PTT, fibrinogen, d-dimer · All patients

    SITC's exclusion of disseminated intravascular coagulation, a competing consumptive cause with a different treatment.

    34172516

  • LDH · All patients

    Part of SITC's work-up; a marker of hemolysis or high cell turnover that points away from isolated ITP.

    34172516

Grade ladder

Grade 1
Continue the ICIOutpatient

Grade 1 — ASCO's ITP chapter continues the ICPi here: 'Continue ICPi with close clinical follow-up and laboratory evaluation.' This card previously held the drug at grade 1, reading ASCO's cross-organ sentence about 'some' hematologic toxicities onto ITP; the chapter itself places that exception elsewhere on the organ, and the chapter is now held. SITC states no grade-1 ICI action for ITP and does not contradict this. Its management is standard-of-care ITP: steroids at 1 mg/kg. The IVIG and rituximab escalations below are keyed to severity and steroid response, not to a CTCAE rung.

Corticosteroid 1 mg/kg/day (oral)

Taper over 4–6 weeks, starting once: After 4 weeks of prednisone. ASCO's ITP chapter states this taper for this entity — 'orally for 4 weeks followed by taper over 4-6 weeks to the lowest effective dose' — so the window is ASCO's own and closed, not the cross-organ floor.

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 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP.
  • Rituximab — Steroid-refractory ITP — SITC notes it has been successfully managed this way.
  • · Establish and track a baseline platelet count
  • · Exclude DIC and other non-immune causes before attributing the drop to the ICI

Escalate when: Severe thrombocytopenia, bleeding, or no platelet recovery on steroids.

Grade 2
Hold the ICIOutpatient

Grade 2 — ASCO may suspend the ICPi for most grade 2 toxicities. SITC's ITP management does not change by rung: standard-of-care steroids at 1 mg/kg, with IVIG for severe disease.

Corticosteroid 1 mg/kg/day (oral)

Taper over 4–6 weeks, starting once: After 4 weeks of prednisone. ASCO's ITP chapter states this taper for this entity — 'orally for 4 weeks followed by taper over 4-6 weeks to the lowest effective dose' — so the window is ASCO's own and closed, not the cross-organ floor.

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 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP.
  • Rituximab — Steroid-refractory ITP.
  • · Serial platelet counts against baseline
  • · Hematology involvement for a count that does not recover

Escalate when: Progression to severe thrombocytopenia or bleeding.

Grade 3
Hold the ICIConsider admission

Grade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3. For ITP this is where 'severe' typically applies, and SITC adds IVIG at 0.5 g/kg/day for 5 days on top of steroids.

Corticosteroid 1 mg/kg/day (oral)

Taper over 4–6 weeks, starting once: After 4 weeks of prednisone. ASCO's ITP chapter states this taper for this entity — 'orally for 4 weeks followed by taper over 4-6 weeks to the lowest effective dose' — so the window is ASCO's own and closed, not the cross-organ floor.

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 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP — which grade 3 typically represents.
  • Rituximab — Steroid-refractory ITP.
  • · IVIG alongside steroids for severe disease
  • · Platelet transfusion for active bleeding, per hematological standard of care

Escalate when: Life-threatening bleeding or refractoriness to steroids and IVIG.

Grade 4
Discontinue permanentlyAdmit

Grade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, with an endocrine exception that does not apply. SITC's severe-disease management — steroids plus IVIG, with rituximab for refractory disease — is what fills the treatment side.

Corticosteroid 1 mg/kg/day (oral)

Taper over 4–6 weeks, starting once: After 4 weeks of prednisone. ASCO's ITP chapter states this taper for this entity — 'orally for 4 weeks followed by taper over 4-6 weeks to the lowest effective dose' — so the window is ASCO's own and closed, not the cross-organ floor.

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 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP.
  • Rituximab — Steroid-refractory ITP.
  • · Admission for severe or bleeding thrombocytopenia
  • · Permanent discontinuation of the ICI

Escalate when: Already the top rung. Refractory ITP beyond steroids, IVIG and rituximab is outside what the chapters held here state.

Rechallenge

Avoid rechallenge

SITC states no ITP-specific rechallenge rule. The organ-level figure it does give — 43% recurrence when a small group with prior haem-irAEs was re-exposed (n=7) — is a caution rather than a recommendation, and is carried on this anchor card's citation. The stance is the conservative reading of a 43% recurrence signal and a phenotype whose severe form needs IVIG, not a documented protocol; the recurrence field is null because the 43% is an all-haem figure, not an ITP-specific one.

  • · Platelet recovery and a hematology assessment before any re-exposure is contemplated

Deliberately not carried

  • Where sources differ — Empty although TWO chapters are now held for this entity. ASCO's Table 8 section 8.6 and SITC's ITP recommendations are both read, and where they touch the same decision they do not conflict: ASCO continues the ICPi at grade 1 and SITC states no grade-1 ICI action, so there is no second position to set against it. ASCO's taper and SITC's dose are complementary rather than competing, and both are carried on the rungs with their own citations.
  • Reported frequency — No ITP-specific incidence is stated in any source held here. The <1% carried is the organ-level frequency across all haem-irAEs, and its population line says so. The Delanoy cohort's '9 of 35 cases were ITP' is a composition of a grade-2-or-worse case series, not a rate, and is not entered as a framing.
  • Grade 3 or higher share — Null. The Delanoy cohort was grade-2-or-worse by inclusion and 71% reached grade 4 — a figure shaped by the selection criterion, not a grade ≥3 rate of ITP, so it is described on the organ header rather than encoded as this entity's severity rate.
  • Mortality — Null. The two deaths in the Delanoy cohort were from febrile neutropenia, not ITP; attributing them here would misplace a neutropenia outcome. They are carried on the neutropenia card.
  • Median time to onset — SITC states the median in days (41). It is not converted to a weeks median; the note carries it in the published unit.
  • Corticosteroid taper — No longer without a source: ASCO's ITP chapter states a taper for this entity — four weeks of prednisone, then a taper over 4-6 weeks to the lowest effective dose — so every rung now shows that closed window rather than the cross-organ floor. SITC gives the 1 mg/kg dose and no taper. The step size and interval are still empty: ASCO gives the window and no cadence, and inventing one would print a number no source states.
  • 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 blood card.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: That immune thrombocytopenia must be separated from the many non-immune causes of a low platelet count in cancer; the value of a baseline platelet count; the 41-day median onset and 4-week median resolution; the diagnostic work-up; and the graded management — steroids at 1 mg/kg, IVIG 0.5 g/kg/day for 5 days added for severe disease, and rituximab for steroid-refractory disease. This anchor citation also carries the organ-level context spans: the <1% frequency across 745 anti-PD-(L)1 patients, the 43% recurrence on rechallenge (n=7), and the 2-9 week typical resolution window.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 8 section 8.6 ITP chapter, and only that entity: the grade-1 rule (continue the ICPi with close clinical follow-up and laboratory evaluation), and the grade-2 management ASCO carries up to grades 3-4 through "As per G2." — hold with interruption until the event reverts to grade 1, prednisone 1 mg/kg/day (range 0.5-2) orally for 4 weeks followed by a taper over 4-6 weeks to the lowest effective dose, IVIG alongside corticosteroids where a faster platelet rise is needed and at 1 g/kg as a one-time dose, a hematology consult, dexamethasone 40 mg daily for 4 days as an alternative, and rituximab or a thrombopoietin receptor agonist after corticosteroid or IVIG failure.Supporting text: the full text
  • Delanoy N, et al. (2019) Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study.Cited for: The 0.5% frequency in the prospective registry; that neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia were the three commonest presentations at nine patients (26%) each; the grade skew (71% reaching grade 4); the two febrile-neutropenia deaths; and the 60% resolution. A cohort of 35 grade-2-or-worse cases assembled from three French pharmacovigilance databases.Supporting text: the PubMed abstract (checkable at the link above)

ICI-associated autoimmune hemolytic anemia

Also called: AIHA · autoimmune hemolytic anemia · immune hemolytic anemia · checkpoint inhibitor hemolysis

Among the commonest hematological irAEs, arriving around a median of 50 days and — unusually for this organ — carrying a class signal: anti-PD-(L)1 therapy raises the risk more than anti-CTLA-4. Managed as standard-of-care hemolytic anemia, with IVIG added when severe disease resists steroids.

RareSeriousonset: weeks 6–12

Severity and class

  • Greater with anti-PD-(L)1 than anti-CTLA-4 — Relative risk of AIHA by ICI class

    of Not stated — SITC gives the direction and 'significantly greater' without a numerator or ratio · SITC chapter statement. A qualitative comparison, retained because a class signal is unusual among the heme phenotypes; the value and denominator fields say no number was published

    guideline · 34172516

Onset

SITC states a median onset of 50 days and a median time to resolve below grade 2 of 2 weeks. Stored in the units the source printed; 50 days is not converted to a weeks median.

Presentation

  • · Anemia with laboratory hemolysis — the picture SITC manages as autoimmune hemolytic anemia
  • · Fatigue and the general symptoms of a falling hemoglobin
  • · Often steroid-responsive, with a median resolution of about 2 weeks below grade 2

Differential

  • · Bleeding and iron deficiency, and the other non-hemolytic anaemias of cancer
  • · Chemotherapy myelosuppression
  • · Microangiopathic hemolysis (TMA), separated on the blood smear
  • · Aplastic anemia and pure red cell aplasia, the marrow-failure phenotypes SITC manages differently

Work-up

  • CBC with differential and reticulocyte count · All patients

    Establishes the anemia and the marrow's response; a hemolytic anemia is typically reticulocytic, separating it from PRCA.

    34172516

  • Blood smear evaluation · All patients

    Looks for spherocytes and excludes a microangiopathic (TMA) picture that would change the diagnosis and treatment.

    34172516

  • Hemolysis markers — LDH, haptoglobin, bilirubin — with a direct antiglobulin test · All patients

    Confirms hemolysis and its autoimmune basis. SITC frames the entity as autoimmune hemolytic anemia; the DAT is the test that establishes the 'autoimmune' half of that name.

    34172516

Grade ladder

Grade 1
Continue the ICIOutpatient

Grade 1 — ASCO's hemolytic-anemia chapter continues the ICPi here: 'Continue ICPi with close clinical follow-up and laboratory evaluation.' This card previously held the drug at grade 1, reading ASCO's cross-organ sentence about 'some' hematologic toxicities onto this entity; ASCO's own Table 8 places that exception elsewhere on the organ, and the chapter is now held. ASCO states no grade-1 corticosteroid; the dose shown is SITC's standard-of-care AIHA management, unchanged, with IVIG added for severe disease that does not respond. The escalation is keyed to severity and steroid response rather than to a CTCAE rung.

Corticosteroid 1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. SITC gives the 1 mg/kg 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.

Second line

  • IVIG 0.5 g/kg/day for 5 days, added to steroids — Severe AIHA that does not respond to steroids.
  • · Establish hemolysis with LDH, haptoglobin and a direct antiglobulin test
  • · Exclude a microangiopathic cause on the smear before treating as autoimmune

Escalate when: Falling hemoglobin despite steroids, or a transfusion requirement.

Grade 2
Hold — consider permanent discontinuationOutpatient

Grade 2 — ASCO's hemolytic-anemia chapter is specific here and stronger than its cross-organ default: 'Hold ICPi and strongly consider permanent discontinuation.' The dose is ASCO's own for this rung, 0.5-1 mg/kg/d prednisone equivalents — HALF the flat 1 mg/kg this card previously carried at every grade from SITC. SITC's AIHA management does not change by rung; ASCO's does, and the chapter is now held.

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.

Second line

  • IVIG 0.5 g/kg/day for 5 days, added to steroids — Severe steroid-refractory AIHA.
  • · Serial hemoglobin and hemolysis markers
  • · Transfusion support as clinically required

Escalate when: Progression to severe anemia or steroid non-response.

Grade 3
Discontinue permanentlyConsider admission

Grade 3 — ASCO's hemolytic-anemia chapter permanently discontinues here: 'Permanently discontinue ICPi.' That is stronger than the suspend-at-grade-3 this card previously showed from ASCO's cross-organ ladder, and the chapter is now held. ASCO's dose for this rung is prednisone 1-2 mg/kg/d, which it allows 'oral or IV equivalent depending on symptoms or speed of development' — the route below is the oral form and the intravenous equivalent is permitted at the same dose. ASCO also asks for a hematology consult and clinical judgment about admission. SITC adds IVIG at 0.5 g/kg/day for 5 days when steroids do not control it.

Corticosteroid 1–2 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.

Second line

  • IVIG 0.5 g/kg/day for 5 days, added to steroids — Severe steroid-refractory AIHA.
  • · IVIG alongside steroids for severe disease
  • · Transfusion for symptomatic or severe anemia

Escalate when: Life-threatening anemia or hemodynamic compromise.

Grade 4
Discontinue permanentlyAdmit

Grade 4 — ASCO's hemolytic-anemia chapter discontinues permanently and admits, which agrees with its cross-organ rule and is now stated for this entity rather than inferred from it. ASCO's grade-4 dose is intravenous: 'IV prednisone corticosteroids 1-2 mg/kg/d' — the route changes here, where at grade 3 it was oral or intravenous by symptoms and speed. SITC's severe-disease treatment — steroids plus IVIG — is the treatment side, and ASCO adds rituximab, IVIG, ciclosporin, infliximab, MMF or ATG where corticosteroids fail.

Corticosteroid 1–2 mg/kg/day (intravenous)

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 0.5 g/kg/day for 5 days, added to steroids — Severe steroid-refractory AIHA.
  • · Admission and transfusion support for life-threatening anemia
  • · Permanent discontinuation of the ICI

Escalate when: Already the top rung. AIHA refractory to steroids and IVIG is beyond what the chapters held here state.

Rechallenge

Avoid rechallenge

SITC states no AIHA-specific rechallenge rule. Its organ-level 43% recurrence figure on re-exposure is a caution carried on the ITP anchor card, not an AIHA number. Given a phenotype with a class signal toward the very agents most patients would be re-exposed to, the stance is the conservative reading; recurrence is null because no AIHA-specific figure exists here.

  • · Resolution of hemolysis and hematology input before any re-exposure is considered

Deliberately not carried

  • Where sources differ — Empty although TWO chapters are now held for this entity. ASCO's Table 8 section 8.1 and SITC's AIHA recommendations are both read. They differ in emphasis rather than direction — ASCO grades the corticosteroid dose and the ICI action by rung where SITC states one management for severe disease — and ASCO's per-rung positions are carried on the ladder rather than as a disagreement, because SITC states no competing rung-level position to set against them.
  • Reported frequency — EMPTY. No AIHA-specific rate is stated in any source held here, and the organ-level <1% is carried once on the ITP anchor rather than repeated. The Delanoy cohort's '9 of 35' is a case-series composition, not a rate.
  • Grade 3 or higher share — Null. No grade ≥3 rate for AIHA is stated here; the Delanoy grade skew is selection-shaped and organ-level.
  • Mortality — Null. The Delanoy deaths were from febrile neutropenia, not AIHA.
  • Median time to onset — SITC states the median in days (50). It is not converted to a weeks median.
  • Corticosteroid taper — Neither chapter states a taper for hemolytic anemia. SITC gives its dose and no taper; ASCO's section 8.1 states doses by rung and no taper window — unlike its ITP section, which does. Every rung therefore still shows ASCO's cross-organ floor, rendered open-ended, labeled as ASCO's, with the cadence fields empty together.
  • Second-line therapy beyond IVIG — SITC's AIHA recommendation names steroids and IVIG and stops there. Rituximab and splenectomy are standard in primary AIHA but are not in the chapter held here, so they are not carried — the ITP card's rituximab is scoped to ITP, where SITC does name it.
  • Linked society recommendations — Left empty — the recommendation this atlas stores for ASCO and for SITC is scoped to ICI-related kidney injury.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: That autoimmune hemolytic anemia is among the commonest haem-irAEs; its 50-day median onset and 2-week median resolution; the greater risk with anti-PD-(L)1 than anti-CTLA-4; and the graded management — steroids at 1 mg/kg, with IVIG 0.5 g/kg/day for 5 days added for severe steroid-refractory disease.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 8 section 8.1 hemolytic-anemia chapter, and only that entity: the grade-1 rule (continue the ICPi with close clinical follow-up and laboratory evaluation), the grade-2 hold with permanent discontinuation strongly considered and 0.5-1 mg/kg/d prednisone equivalents, the grade-3 permanent discontinuation with prednisone 1-2 mg/kg/d oral or IV and a hematology consult, and the grade-4 permanent discontinuation with IV prednisone 1-2 mg/kg/d and the escalation list.Supporting text: the full text
  • Delanoy N, et al. (2019) Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study.Cited for: The 0.5% frequency in the prospective registry; that neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia were the three commonest presentations at nine patients (26%) each; the grade skew (71% reaching grade 4); the two febrile-neutropenia deaths; and the 60% resolution. A cohort of 35 grade-2-or-worse cases assembled from three French pharmacovigilance databases.Supporting text: the PubMed abstract (checkable at the link above)

ICI-associated neutropenia

Also called: immune-related neutropenia · checkpoint inhibitor neutropenia · immune neutropenia · agranulocytosis

The latest-onset of the common hematological irAEs — a median of 10.5 weeks — and the one that killed in the reference cohort: both deaths there were from febrile neutropenia. Managed with steroids AND G-CSF, and gated first by the question of whether the low count is immune at all.

RareCriticalonset: weeks 6–12

Severity and class

  • 2 (6%) — Deaths from febrile neutropenia in the reference cohort

    of 2 of 35 grade-2-or-worse haem-irAE cases (both deaths were febrile neutropenia) · French three-registry cohort of anti-PD-(L)1 haem-irAEs. Both deaths in the whole hematological cohort were neutropenic, which is why the figure sits on this card and not the others — but it is a count in a selected case series, not a case-fatality rate for ICI neutropenia

    cohort · 30528137

Onset

SITC states a median onset of 10.5 weeks — the latest of the common hematological phenotypes, against 41 days for ITP and 50 days for AIHA. This is one of the few onset figures a source published directly in weeks, so it is stored as a weeks median rather than left null.

Presentation

  • · A falling neutrophil count, often the latest-onset of the common haem-irAEs
  • · Fever and infection — the complication that makes this phenotype dangerous, and the one that caused both deaths in the reference cohort
  • · Frequently detected on routine counts before infection supervenes

Differential

  • · Chemotherapy-induced myelosuppression — SITC makes separating this from immune neutropenia the first step in a chemo-immunotherapy patient, because the treatments diverge
  • · Sepsis with consumption, and other drugs
  • · Aplastic anemia and broader marrow failure, distinguished by the reticulocyte count and smear
  • · Large granular lymphocyte expansions and other primary hematological causes

Work-up

  • CBC with differential · All patients

    Establishes the neutropenia and whether it is isolated or part of a broader cytopenia.

    34172516

  • Blood smear evaluation · All patients

    SITC's second work-up item; looks for a primary hematological cause and for evidence of marrow failure.

    34172516

  • Distinction from chemotherapy myelosuppression · All patients

    In a chemo-immunotherapy patient SITC makes this the pivotal judgment: immune neutropenia is treated with immunosuppression and G-CSF, chemotherapy myelosuppression is not, so the two must be told apart before treating.

    34172516

Grade ladder

Grade 1
Hold the ICIOutpatient

Grade 1 — ASCO names hematologic toxicity among its grade-1 exceptions. SITC's management is standard-of-care immune neutropenia: steroids at 1 mg/kg WITH G-CSF, once the count is judged immune rather than chemotherapy-driven.

Corticosteroid 1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Not stated for this entity. SITC gives the 1 mg/kg 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.

Second line

  • G-CSF, alongside steroids — Part of SITC's first-line management of immune neutropenia, not a rescue — the feature that distinguishes this cytopenia's treatment from ITP and AIHA.
  • · Separate immune neutropenia from chemotherapy myelosuppression before treating
  • · Neutropenic-fever precautions — the infection is what kills

Escalate when: Fever, infection, or a deepening neutrophil count.

Grade 2
Hold the ICIOutpatient

Grade 2 — ASCO may suspend the ICPi for most grade 2 toxicities. SITC's management does not change by rung: steroids at 1 mg/kg with G-CSF.

Corticosteroid 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.

Second line

  • G-CSF, alongside steroids — First-line for immune neutropenia.
  • · Low threshold for antibiotics if febrile
  • · Serial counts; watch for evolution into broader marrow failure

Escalate when: Febrile neutropenia or progression to a severe count.

Grade 3
Hold the ICIConsider admission

Grade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3. Severe neutropenia is where the infection risk becomes acute; SITC's steroids-plus-G-CSF stands, now with admission for fever.

Corticosteroid 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.

Second line

  • G-CSF, alongside steroids — First-line for immune neutropenia.
  • · Admit and start broad-spectrum antibiotics for neutropenic fever
  • · G-CSF with steroids per SITC's standard of care

Escalate when: Febrile neutropenia with instability, or evolution to aplastic anemia.

Grade 4
Discontinue permanentlyAdmit

Grade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, with an endocrine exception that does not apply. Grade 4 neutropenia is the setting in which both cohort deaths occurred, from febrile neutropenia.

Corticosteroid 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.

Second line

  • G-CSF, alongside steroids — First-line for immune neutropenia.
  • · Admission with neutropenic-sepsis management — the failure mode that caused both cohort deaths
  • · Permanent discontinuation of the ICI

Escalate when: Already the top rung. Refractory immune neutropenia beyond steroids and G-CSF is outside what the chapters held here state.

Rechallenge

Avoid rechallenge

SITC states no neutropenia-specific rechallenge rule, and the organ-level 43% recurrence figure is carried on the ITP anchor. This is the hematological phenotype that proved fatal in the reference cohort, both deaths from febrile neutropenia, so the conservative stance is the more strongly indicated one; recurrence is null because no neutropenia-specific figure is stated here.

  • · Full count recovery and hematology input before any re-exposure is considered

Deliberately not carried

  • Where sources differ — Empty because only one society chapter is held for THIS ENTITY. ASCO's Table 8 has sections read for hemolytic anemia and for ITP, but none for neutropenia, so ASCO reaches this card only through its cross-organ ladder quoted from the abstract — which is not a hematology position for this phenotype.
  • Reported frequency — EMPTY. No neutropenia-specific rate is stated here, and the organ-level <1% sits once on the ITP anchor. The Delanoy '9 of 35' is a case-series composition, not a rate.
  • Grade 3 or higher share — Null. No grade ≥3 rate for neutropenia is stated here; the cohort's grade skew is selection-shaped and organ-level.
  • Mortality — evidence basis — The mortality figure is carried as a cohort count (2 of 35), and the population line states plainly that it is a count in a selected grade-2-or-worse case series — both hematological deaths in that cohort were neutropenic — not a case-fatality rate for ICI neutropenia. It is on this card rather than the organ header because the deaths were specifically from this phenotype.
  • Corticosteroid taper — SITC gives the 1 mg/kg dose and no taper for neutropenia. Every rung shows ASCO's cross-organ floor, labeled as ASCO's, with the cadence fields null together.
  • Linked society recommendations — Left empty — the recommendation this atlas stores for ASCO and for SITC is scoped to ICI-related kidney injury.

Sources

  • Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: The 10.5-week median onset of ICI-related neutropenia and its infection risk; the need to distinguish immune neutropenia from chemotherapy myelosuppression in chemo-immunotherapy patients; the work-up; and the management — steroids at 1 mg/kg WITH G-CSF, which is the feature that sets it apart from the other cytopenias.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 cross-organ ladder, cited as that and nothing more: suspension for most grade 2, high-dose corticosteroids at grade 3, permanent discontinuation at grade 4. Its grade-1 sentence carries an exception for "some" hematologic toxicities and is NOT the grade-1 rule for the entities on this organ — ASCO's own Table 8 continues the ICPi at grade 1 for both ITP and hemolytic anemia, and those chapters are now held here per entity.Supporting text: the PubMed abstract (checkable at the link above)
  • Delanoy N, et al. (2019) Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study.Cited for: The 0.5% frequency in the prospective registry; that neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia were the three commonest presentations at nine patients (26%) each; the grade skew (71% reaching grade 4); the two febrile-neutropenia deaths; and the 60% resolution. A cohort of 35 grade-2-or-worse cases assembled from three French pharmacovigilance databases.Supporting text: the PubMed abstract (checkable at the link above)

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