Daratumumab-based therapy for newly diagnosed multiple myeloma patients with renal impairment：a multicenter retrospective study from China

Abstract INTRODUCTION Renal impairment (RI) is a frequent complication in newly diagnosed multiple myeloma (NDMM). Recovery of renal function is associated with prolonged survival for NDMM. Daratumumab, a monoclonal antibody targeting CD38, is highly effective for both relapsed or refractory MM and NDMM. While daratumumab demonstrates remarkable efficacy for MM with RI in clinical trials, its impact on renal responses in the first-line setting is not as well described. AIM To evaluate the renal and hematologic response of daratumumab-based therapy as first-line treatment in NDMM with RI in this retrospective, multi-center study. METHOD A database search was conducted to identify patients who received daratumumab-based therapy after inpatient admission between December 2018 and March 2025. Included in the analysis were adult patients with newly diagnosed MM who met all the following criteria: presenting with RI (sCr ≥177 μmol/L and/or eGFR <40 mL/min/1.73 m2 by CKD-EPI). And RI was caused by MM cast nephropathy and confirmed by biopsy or clinical judgement. We assessed renal and MM disease response according to the International Myeloma Working Group (IMWG) criteria. Follow up was determined by reverse KM method. Progression-free and overall survival were calculated from the date of the first dose of daratumumab. RESULTS Between Jan 01,2019 and Mar 07,2025, 140 patients were identified across 22 centers, with a median age of 65 years (range: 34-92). Of the 126 patients with available FISH cytogenetic data, 78 (61.9%) patients were defined as R-ISS III and 29 (23.0%) patients had high-risk cytogenetic abnormalities [t(4;14), t(14;16), or del(17p)]. Median serum creatine level and eGFR were 332.8μmol/L (range: 130.7-1341.0) and 14.8 ml/min (range: 2.5-39.8), respectively. There were 28/140 (20.0%) patients requiring dialysis at diagnosis. The daratumumab-based regimens included dara-Vd in 71 patients (50.7%), dara-Rd in 12 patients (8.5%), dara-VRd in 17 patients (12.1%), dara-VPD in 16 patients (11.4%) and other daratumumab-based regimens in 17.1% patients. Thirty-six patients (25.7%) underwent first-line ASCT. The renal ORR at 3 months was 76.4% (including 13.6% renal PR, and 28.6% renal CR). The best renal ORR was 87.9% (20.7% renal PR, 36.4% renal CR). The 3-month hematological ORR was 93.6% (131/140), with 95 of 140 patients (67.9%) achieving at least very good partial response (VGPR) and 34 (24.3%) achieving CR or stringent CR. The best ORR was 93.6% (131/140), among which 77.1% achieved at least VGPR and 47.9% achieved CR/stringent CR. With a median follow up of 13.3 months, the estimated median progression-free survival (PFS) was 29.8 (95% CI 21.9-37.7) months, whereas median overall survival (OS) has not been reached. CONCLUSION Daratumumab combinations in first-line therapy are very effective for NDMM patients with RI.