Drugs used in the setting of cancer and associated with MAHA
Cancer therapy . | Potential mechanism of TMA and management . |
---|---|
Checkpoint inhibitors (eg, ipilimumab) | ADAMTS13 deficiency (ADAMTS13 inhibitor present); responds to PEX |
Lenalidomide | ADAMTS13 deficiency (anti-ADAMTS13 Ab in 4/5 cases); responds to PEX |
Gemcitabine | Dose-dependent endothelial damage, predominantly renal glomerular arterioles/capillaries; may respond to complement inhibition |
Mitomycin C | Dose-dependent toxicity, microthrombi in glomerular arterioles/capillaries; may respond to complement inhibition |
VEGF inhibitors (eg, bevacizumab, aflibercept) | Dose-dependent toxicity; hypertension; microthrombi limited to glomerular capillaries |
Proteosome inhibitors (eg, bortezomib, carfilzomib) | Renal impairment and hypertension with TMA; favorable response to stopping culprit drug; may respond to complement inhibition; role of PEX? |
Pentostatin | Dose-dependent toxicity at high doses |
EGFR inhibitor cetuximab | Renal TMA with nephrotic syndrome |
Calcineurin inhibitors (eg, ciclosporin, tacrolimus) | TMA primarily affects glomerular arterioles; reducing dose or stopping drug can improve or reverse the TMA |
mTOR inhibitors (eg, sirolimus, everolimus) | Renal TMA; can occur in patients on calcineurin inhibitor–free regimen |
Platinum-based agents (eg, oxaliplatin) | Drug-dependent antibodies against platelets and red cells |
Hormone therapies (eg, tamoxifen) | Precipitation of congenital TTP/association with immune TTP; close ADAMTS13 monitoring required if history of TTP |
Cancer therapy . | Potential mechanism of TMA and management . |
---|---|
Checkpoint inhibitors (eg, ipilimumab) | ADAMTS13 deficiency (ADAMTS13 inhibitor present); responds to PEX |
Lenalidomide | ADAMTS13 deficiency (anti-ADAMTS13 Ab in 4/5 cases); responds to PEX |
Gemcitabine | Dose-dependent endothelial damage, predominantly renal glomerular arterioles/capillaries; may respond to complement inhibition |
Mitomycin C | Dose-dependent toxicity, microthrombi in glomerular arterioles/capillaries; may respond to complement inhibition |
VEGF inhibitors (eg, bevacizumab, aflibercept) | Dose-dependent toxicity; hypertension; microthrombi limited to glomerular capillaries |
Proteosome inhibitors (eg, bortezomib, carfilzomib) | Renal impairment and hypertension with TMA; favorable response to stopping culprit drug; may respond to complement inhibition; role of PEX? |
Pentostatin | Dose-dependent toxicity at high doses |
EGFR inhibitor cetuximab | Renal TMA with nephrotic syndrome |
Calcineurin inhibitors (eg, ciclosporin, tacrolimus) | TMA primarily affects glomerular arterioles; reducing dose or stopping drug can improve or reverse the TMA |
mTOR inhibitors (eg, sirolimus, everolimus) | Renal TMA; can occur in patients on calcineurin inhibitor–free regimen |
Platinum-based agents (eg, oxaliplatin) | Drug-dependent antibodies against platelets and red cells |
Hormone therapies (eg, tamoxifen) | Precipitation of congenital TTP/association with immune TTP; close ADAMTS13 monitoring required if history of TTP |
Ab, antibody; EGFR, endothelial growth factor receptor; mTOR, mammalian target of rapamycin.