Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Anti-CD38 antibody
Isatuximab
Sarclisa · Isa
An anti-CD38 antibody effective even with reduced GFR; tumor lysis on rapid myeloma response is the renal caveat.
MildAnti-CD38 antibody · approved 2020
Relapsed/refractory multiple myeloma
Signature kidney injury
Prerenal / Hemodynamic AKI
Direct nephrotoxicity is uncommon; tumor lysis can occur with high tumor burden. In the ICARIA-MM and IKEMA renal-impairment subgroups, isatuximab regimens remained effective and produced renal responses; real-world data show inferior PFS with eGFR <60 but persistent benefit.
Source: Dimopoulos et al., Leukemia 2020 (ICARIA-MM renal subgroup)
Mechanism of kidney injury
Rapid plasma-cell lysis can precipitate tumor-lysis AKI in high-burden disease; otherwise renal effects are hemodynamic/infusion-related. As with daratumumab, controlling myeloma reduces nephrotoxic free light-chain load and cast nephropathy, supporting and often improving renal function in renal-impaired patients.
Clinical presentation
Generally stable renal function with myeloma response (renal response in a meaningful fraction of renally impaired patients); possible tumor-lysis labs in bulky disease; infusion reactions occur but are not nephrotoxic.
Onset
Tumor lysis (if any) early; renal benefit over the treatment course.
Reversibility
Reversible
Anticancer mechanism
Anti-CD38 IgG1 monoclonal antibody binding a distinct CD38 epitope from daratumumab; it induces plasma-cell death via ADCC, CDC, antibody-dependent phagocytosis and notably strong direct, CD38-enzyme-inhibiting pro-apoptotic effects, used with pomalidomide/dexamethasone (ICARIA) or carfilzomib/dexamethasone (IKEMA) in relapsed/refractory multiple myeloma.
Management
Standard TLS management if it occurs; usable in renal impairment without specific renal dose adjustment. Aim for rapid disease control to support renal recovery.
Risk factors
- High tumor burden
- Baseline cast nephropathy / high free light-chain burden
- Volume depletion
Prevention
- TLS risk assessment with hydration and urate-lowering therapy in high-burden disease
- Maintain effective myeloma therapy to protect/recover renal function
- Infusion-reaction premedication
Note · As with daratumumab, the net renal effect in myeloma is often favorable; tumor lysis is the principal direct renal risk. Isatuximab likewise interferes with CD38-based serologic testing — alert the blood bank.
Clinical depth
Renal dose adjustment
No renal dose adjustment; antibody clearance is target-mediated/reticuloendothelial, not renal. Standard weight-based dosing (10 mg/kg) is used across renal-function strata; ICARIA-MM and IKEMA included patients with renal impairment.
Dialyzability & ESKD dosing
Not dialyzed — a large IgG1 antibody not removed by HD/PD; standard dosing in ESKD. Dialysis treats TLS complications, not drug levels.
Differential diagnosis
Distinguish a creatinine change from underlying myeloma kidney disease (cast nephropathy, light-chain effects, hypercalcemia) and from tumor lysis rather than a direct drug effect. Improving renal function usually reflects disease response.
Monitoring
- Serum free light chains / paraprotein and renal function (track renal response)
- TLS labs at initiation in high-burden disease
- Infusion-reaction monitoring (first infusion highest risk)
- Note CD38-antibody interference with the antiglobulin crossmatch — inform the blood bank
Key trials & series
- Dimopoulos et al., Leukemia 2020 — ICARIA-MM renal-impairment subgroup (renal response, retained efficacy)
- Capra et al., Haematologica 2022 — IKEMA renal-impairment subgroup analysis
- Attal et al., Lancet 2019 — ICARIA-MM registrational parent trial
Clinical pearls
- Isatuximab retains efficacy and yields renal responses in renal-impaired myeloma (ICARIA/IKEMA subgroups) — no CrCl dose adjustment.
- Tumor lysis in high-burden disease is the main direct renal risk — prophylax at initiation.
- Like daratumumab, isatuximab confounds the antibody crossmatch via red-cell CD38 — notify transfusion services.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkIsatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis.Dimopoulos MA et al. · Leukemia 2020 · PMID 32444867Dedicated ICARIA-MM renal-impairment subgroup with renal response and retained efficacy.PMIDIsatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis.Capra M et al. · Haematologica 2022 · PMID 34647444IKEMA renal-impairment subgroup with renal-response data.PMIDIsatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study.Attal M et al. · Lancet 2019 · PMID 31735560ICARIA-MM registrational parent trial defining efficacy and safety.PMIDEvaluation of anti-CD38 monoclonal antibody-based immunotherapy in multiple myeloma with renal insufficiency: a systematic review and meta-analysis.Bai H et al. · Ther Adv Hematol 2025 · PMID 39963097Meta-analysis supporting anti-CD38 antibody benefit (including isatuximab) in renal insufficiency.PMIDEfficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset.Djebbari F et al. · Hemasphere 2022 · PMID 35651713Real-world isatuximab data showing efficacy across renal-function strata (inferior PFS with eGFR <60).PMIDAnti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes.Leleu X et al. · Ann Hematol 2022 · PMID 35943588Mechanistic/clinical review of isatuximab vs daratumumab including renal-impairment evidence.
Related agents
Other agents sharing the same signature kidney injury.