Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Antibody-drug conjugate (CD22/calicheamicin)
Inotuzumab ozogamicin
Besponsa · InO
A CD22/calicheamicin conjugate for ALL — tumor lysis and veno-occlusive disease drive its renal risk.
ModerateAntibody-drug conjugate · approved 2017
Acute lymphoblastic leukemia
Signature kidney injury
Prerenal / Hemodynamic AKI
Direct nephrotoxicity is not a prominent signal. AKI is chiefly secondary to tumor lysis and to hepatic sinusoidal obstruction syndrome/veno-occlusive disease (VOD) — a notable, sometimes fatal complication, particularly around subsequent allogeneic stem-cell transplant. Renal-specific incidence is not quantified.
Source: Kantarjian et al., N Engl J Med 2016 (INO-VATE)
Mechanism of kidney injury
Indirect: rapid lysis of bulky ALL causes tumor lysis with crystal nephropathy and electrolyte shifts; calicheamicin injury to hepatic sinusoidal endothelium produces VOD with fluid overload and hepatorenal-pattern AKI, with markedly elevated VOD risk after allogeneic transplant (and with dual-alkylator conditioning). Direct tubular toxicity is not a notable clinical signal.
Clinical presentation
Tumor-lysis labs with AKI early in therapy; with VOD, weight gain, ascites, hyperbilirubinemia, hepatomegaly and rising creatinine with low urine sodium, especially in the peri-transplant period.
Onset
Early — tumor lysis during initial therapy; VOD typically peri-transplant.
Reversibility
Variable
Anticancer mechanism
Antibody-drug conjugate targeting CD22 and delivering the DNA-damaging calicheamicin payload via a hydrolyzable linker. Approved for relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Management
Tumor-lysis management; for VOD, supportive care and defibrotide with careful fluid/renal management; supportive AKI care including dialysis if severe.
Risk factors
- High leukemic burden
- Subsequent allogeneic stem-cell transplant
- Dual-alkylator conditioning
- Hepatic dysfunction
- Volume depletion
- Pre-existing CKD
Prevention
- Tumor lysis prophylaxis (hydration, allopurinol/rasburicase)
- Limit cycles before transplant and avoid dual-alkylator conditioning to reduce VOD
- Hepatic (LFTs, weight) and renal monitoring
Note · Renal injury is mediated by tumor lysis and VOD rather than direct tubular toxicity; VOD risk is heightened around transplant.
Clinical depth
Renal dose adjustment
No specific renal dose adjustment; decisions are driven by hepatic function/VOD risk rather than renal clearance. Calicheamicin is hepatically handled.
Dialyzability & ESKD dosing
Not appreciably dialyzed (large ADC; protein-bound calicheamicin). HD/CRRT in VOD supports AKI, not drug removal.
Differential diagnosis
Tumor lysis AKI (early, electrolyte signature) versus VOD hepatorenal AKI (jaundice, weight gain, ascites, low urine sodium) versus sepsis/nephrotoxin ATN. VOD risk is the defining peri-transplant concern.
Monitoring
- LFTs (bilirubin) and daily weight for VOD, especially around transplant
- Tumor lysis labs during initial therapy
- Serum creatinine and volume status in evolving VOD
Key trials & series
- INO-VATE (Kantarjian NEJM 2016, R/R ALL; VOD signal)
- Jabbour Lancet Haematol 2023 (mini-hyper-CVD + inotuzumab; long-term VOD data)
Clinical pearls
- Minimize inotuzumab cycles before allogeneic transplant and avoid dual-alkylator conditioning - both reduce the VOD that drives hepatorenal AKI.
- Like gemtuzumab, the calicheamicin ADCs threaten the kidney via the liver (VOD) and the tumor (lysis), not the tubule.
- Early defibrotide is the key intervention once VOD with renal involvement is recognized.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of antibody-drug conjugate (cd22/calicheamicin)s.
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression (payload-dependent)
Ophthalmic
Keratopathy, uveitis, retinopathy
- Keratopathy (belantamab, mirvetuximab, tisotumab)
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Interstitial lung disease (deruxtecan ADCs)
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (MMAE payloads)
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkInotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia.Kantarjian HM et al. · N Engl J Med 2016 · PMID 27292104INO-VATE phase III establishing efficacy and the veno-occlusive disease signal.PMIDMini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial.Jabbour E et al. · Lancet Haematol 2023 · PMID 37187201Long-term data including VOD with inotuzumab-containing regimens.PMIDDefibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.Richardson PG et al. · Expert Rev Clin Pharmacol 2018 · PMID 29301447Defibrotide for VOD/SOS with renal/pulmonary dysfunction - the key intervention for VOD-related AKI.PMIDTumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.Howard SC et al. · Ann Hematol 2016 · PMID 26758269TLS risk among novel hematologic agents.
Related agents
Other agents sharing the same signature kidney injury.