Introduction: Renal impairment is a common clinical complication in patients with RRMM, and improvement in renal function is associated with better outcomes. In the ongoing phase 1 DREAMM-12 study (NCT04398745), belantamab mafodotin (belamaf) pharmacokinetics appeared to be similar in patients with normal or impaired renal function. In 2 phase 3 trials, DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623), belamaf-containing regimens showed an efficacy benefit vs standard-of-care triplets in patients with RRMM who had received ≥1 prior therapy. Here we present changes in renal function and efficacy outcomes in patients with mild/moderate renal impairment at baseline who were treated with belamaf-containing regimens in DREAMM-7 and DREAMM-8.

Methods: Renal function was assessed using estimated glomerular filtration rate (eGFR) calculated from creatinine values obtained from local laboratory results at screening and throughout the study. Renal function was categorized as normal (≥90 mL/min/1.73 m2), mildly impaired (≥60 to <90 mL/min/1.73 m2), or moderately impaired (≥30 to <60 mL/min/1.73 m2). Patients with severe renal impairment (<30 mL/min/1.73 m2) at screening were ineligible for both trials. In this analysis, an improvement in renal function was defined as an improvement of ≥1 severity category for ≥2 consecutive visits at any point during the study period. PFS and response rates were analyzed in patients who showed improvement in renal function.

Results: In DREAMM-7, of the 234 patients receiving belamaf, bortezomib, and dexamethasone with baseline eGFR assessments, 124 patients had mild renal impairment and 52 patients had moderate renal impairment at baseline. As of October 7, 2024, improvement in renal function was observed in 64 patients (51.6%) with baseline mild impairment and 27 (51.9%) with baseline moderate impairment. In patients with improved renal function, median PFS was 35.7 months (95% CI, 29.0 months-not reached [NR]) and the 18-month PFS rate was 80%. The overall response rate (ORR) in patients with improved renal function was 98% (95% CI, 92.3%-99.7%) and included a complete response or better (≥ CR) minimal residual disease (MRD) negativity rate of 34.1% (31 of 91; 95% CI, 24.5%-44.7%). Of these patients, 64.5% (20 of 31) had sustained MRD negativity for ≥12 months.

In DREAMM-8, of the 155 patients who had baseline eGFR assessments in the belamaf, pomalidomide, and dexamethasone arm, 88 patients had mild renal impairment and 29 patients had moderate renal impairment at baseline. At the January 29, 2024, data cutoff, 37 patients (42.0%) with baseline mild renal impairment and 16 (55.2%) with baseline moderate impairment showed improvement in renal function. In patients with improved renal function, the median PFS was NR (95% CI, 20.6 months-NR) and the 18-month PFS rate was 72%. The ORR in patients with improved renal function was 89% (95% CI, 77.0%-95.7%) and included a ≥ CR MRD negativity rate of 26.4% (14 of 53; 95% CI, 15.3%-40.3%). Of these patients, 35.7% (5 of 14) had sustained MRD negativity for ≥12 months.

Conclusions: Renal impairment is considered a poor prognostic factor in MM, and recovery of renal function is associated with prolonged survival. Across both the DREAMM-7 and DREAMM-8 trials, a substantial proportion of patients treated with belamaf combinations had high rates of improvement in renal function and high response rates with durable PFS.

Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

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2025
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