Safety and efficacy of daratumumab in patients with multiple myeloma and severe renal failure

There has been considerable improvement in the treatment of multiple myeloma (MM), but severe renal impairment (RI) owing to cast nephropathy (CN) is still one of the frequent complications requiring prompt treatment. CN is caused by the precipitation of large amounts of monoclonal free light chain (FLC) in the renal tubules. Therefore, RI treatment in these patients mainly focusses on the rapid reduction of FLC in the circulation, thereby improving renal function; however, there are some exceptions, depending on renal pathology. Daratumumab is an anti-CD38 monoclonal antibody with remarkable efficacy in patients with both newly diagnosed and relapsed/refractory MM in combination with dexamethasone, proteasome inhibitor or immunomodulatory drugs. However, there are no studies of daratumumab in patients with severe renal failure [estimated glomerular filtration rate (eGFR) <15 ml/min/ 1 73 m], except for a few case reports. In the present study, we report on the efficacy and safety of daratumumab in patients with end-stage renal failure at our institution. We retrospectively reviewed 13 consecutive patients with MM admitted to Kameda Medical Center between June 2017 and November 2020 who presented with severe renal failure (≤15 ml/min/1 73 m) and received at least eight doses of daratumumab (16 mg/kg). One patient received four doses of daratumumab and then switched to isatuximab owing to insurance coverage. Daratumumab was used as part of an induction or intensification therapy in patients who did not achieve a complete response (CR). To assess the efficacy of daratumumab on FLC reduction, we measured FLC levels before and 3 and 7 days after daratumumab infusion. Diagnosis and treatment response were assessed using the International Myeloma Working Group (IMWG) criteria. Renal responses were defined according to the IMWG criteria for renal responses to therapy. Cytogenetic abnormalities (CAs) were detected using interphase fluorescence in situ hybridisation. All patients or their family members provided written informed consent, and the study was conducted in accordance with the Declaration of Helsinki and approved by the review board of Kameda Medical Center. Clinical characteristics and previous treatments are shown in Table S1. Six patients were on dialysis at presentation, nine underwent kidney biopsies, and four were diagnosed with CN, three with CN and light chain deposition disease,