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    Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    Category: Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment (Including Dialysis): Results From the Phase I DREAMM-12 Study

    (PA-500) Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment (Including Dialysis): Results From the Phase I DREAMM-12 Study

    Thursday, September 18, 2025

    Introduction:      Belantamab mafodotin (belamaf) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate (ADC) that contains cytotoxic cysteine-monomethyl auristatin-F (cys-mcMMAF). Belamaf has been evaluated in relapsed/refractory multiple myeloma (RRMM) but not in patients (pts) with RRMM and severe renal impairment (RI) or end-stage renal disease (ESRD). The DREAMM-12 study (NCT04398745) assessed belamaf monotherapy in pts with severe RI or ESRD, including pts on dialysis, to provide dose recommendations for these populations.

    Methods:   In this phase I study, 4 groups (Grp) of pts with RRMM (≥2 prior lines of therapy [LOTs]) were treated with belamaf (2.5 mg/kg Q3W): Control Grp1, glomerular filtration rate (GFR [mL/min]) ≥60 (normal/mild RI); Grp2, GFR 15−29 (severe RI); Grp3, GFR < 15 (ESRD not on dialysis); and Grp4, ESRD on dialysis. Endpoints were pharmacokinetics (PK) by non-compartmental analysis (primary), safety (secondary), and efficacy (exploratory).

    Results:   Overall, 36 pts received ≥1 belamaf dose and were eligible for safety analysis. Median (range) age was 72 (48–87) years and median (range) no. of prior LOTs was 4 (2–14). Median (range) no. of treatment cycles was between 2 (for Grp1: [1–23]) and 6 (for Grp3 [2–20] and Grp4 [1–18]). The PK population comprised 29 pts (Grp1, Grp2 and Grp4 n=8 each; Grp3 n=5), with Grp1 and Grp2 matched for body weight and albumin. Cycle 1 concentration–time plots and PK parameters were generally similar for ADC and cys-mcMMAF across groups, except for slightly higher average cys-mcMMAF concentrations in Grp3 including higher average maximum concentration and area under the curve. Exposures between groups were largely overlapping and differences were not considered clinically meaningful. A separate population PK analysis confirmed that ADC and cys-mcMMAF exposures were consistent across RI categories irrespective of dialysis status. Urine PK analysis suggested renal elimination was not the primary route of cys-mcMMAF excretion (median fraction excreted 18% in Grp1). Adverse event (AE) incidence and severity were similar across groups (any AE/grade ≥3 AE: Grp1 100%/70%; Grp2 100%/67%; Grp3 100%/100%; Grp4 100%/75%). There were 7 fatal AEs (Grp1 n=1; Grp2 n=2; Grp3 n=1; Grp4 n=3) with 1 related to belamaf (Grp2). The most common AE classes per pt included eye disorders (Grp1 80%, Grp2 67%, Grp3 60%, Grp4 75%) followed by infections/infestations (50%, 33%, 60%, 75%). Serious AEs were reported in Grp1 in 40%, Grp2 44%, Grp3 60%, and Grp4 50% of pts (infections/infestations were most common [30%, 22%, 40%, 38%]). Investigator-assessed responses (≥partial response) were seen in all groups (overall response rate: Grp1 50%, Grp2 44%, Grp3 60%, Grp4 25%).

    Conclusions:   No clinically meaningful PK, safety, or efficacy differences were seen across RI categories, indicating belamaf dose adjustments are not necessary for pts with mild to severe RI or ESRD, including pts on dialysis.