Efficacy and safety outcomes in patients (pts) with renal impairment in the phase 3 DREAMM-7 and DREAMM-8 trials.

Abstract

7548 Background: Renal impairment is a frequent complication in relapsed/refractory multiple myeloma (RRMM). Results from DREAMM-7 (NCT04246047) showed significant PFS and OS benefit favoring belantamab mafodotin (belamaf), bortezomib, and dexamethasone (BVd) vs daratumumab-Vd (DVd). DREAMM-8 (NCT04484623) showed significant PFS benefit with belamaf, pomalidomide, and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd). In an ongoing phase 1 study (NCT04398745), renal impairment did not impact belamaf pharmacokinetics. We report outcomes in pts with mild/moderate renal impairment from DREAMM-7 and DREAMM-8. Methods: Renal function of eligible pts with RRMM was defined based on estimated glomerular filtration rate (eGFR) derived by local labs at screening: normal (≥90 mL/min/1.73 m 2 ), mild (≥60 to <90 mL/min/1.73 m 2 ), or moderate (≥30 to <60 mL/min/1.73 m 2 ) impairment. Pts with eGFR <30 mL/min/1.73 m 2 were ineligible for these trials. Results: Results included pts with mild/moderate renal impairment in DREAMM-7 (BVd, n=175; DVd, n=183) as of October 2, 2023, and DREAMM-8 (BPd, n=117; PVd, n=109) as of January 29, 2024. Median PFS was NR with BVd vs 12.6 mo with DVd (HR, 0.39; 95% CI, 0.29-0.53) in DREAMM-7 and 24.0 mo with BPd vs 9.7 mo with PVd (HR, 0.52; 95% CI, 0.35-0.76) in DREAMM-8. Belamaf-containing regimens in both trials had numerically higher 18-mo PFS rates, overall response rates (ORRs), and complete response or better (≥CR) rates (Table). OS benefit favored BVd vs DVd (HR, 0.58; 95% CI, 0.39-0.86) and BPd vs PVd (HR, 0.71; 95% CI, 0.46-1.09). Median OS was NR in either arm of both trials. In pts with mild/moderate renal impairment in DREAMM-7, 95% with BVd and 79% with DVd had a grade 3/4 AE. AEs leading to discontinuation of any study drug occurred in 33% and 18%, respectively. Fatal serious AEs occurred in 10% with BVd and 8% with DVd. In DREAMM-8, 90% with BPd and 73% with PVd had a grade 3/4 AE. AEs leading to discontinuation of any study drug occurred in 13% with BPd and 15% with PVd. Fatal serious AEs were observed in 13% and 12%, respectively. Conclusions: In pts with mild/moderate renal impairment, belamaf-containing regimens (BVd and BPd) showed improved efficacy vs standard triplets, indicating they are an efficacious alternative SOC in a broad range of pts with RRMM. Safety results in this pt population were consistent with the ITT populations. ITT population with mild/moderate renal impairment BVd n=175 DVd n=183 BPd n=117 PVd n=109 18-mo PFS rate(95% CI) 0.69 (0.61-0.75) 0.41 (0.33-0.48) 0.61 (0.51-0.70) 0.40 (0.29-0.50) ORR (95% CI), % 86 (79.6-90.5) 74 (67.4-80.5) 76 (67.3-83.5) 72 (62.1-79.8) ≥CR (95%CI), % 34 (26.8-41.2) 15 (10.4-21.3) 38 (29.6-47.9) 13 (7.2-20.6) Safety population with mild/moderate renal impairment BVd n=175 DVd n=183 BPd n=112 PVd n=107 Grade 3/4 AE, % 95 79 90 73 AEs leading to discontinuation of any study drug, % 33 18 13 15 Serious fatal AEs, % 10 8 13 12