DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma

Abstract

Introduction: Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678).

Methods: At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH).

Results: Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3-4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001).

Conclusion: Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.

Keywords: Belamaf; Indirect treatment comparison; MAIC; MAMMOTH; Matching-adjusted; RRMM; Selinexor; Survival.

Fig. 1

PRISMA diagram. ^aThe scope of the SLR was wider than the inclusion criteria of the DREAMM-2 study in order to provide an overview of the treatment landscape. ^bKey comparators to belantamab mafodotin included the following treatments administered as mono- or combination therapies: bortezomib, carfilzomib, daratumumab, dexamethasone, elotuzumab, ixazomib, lenalidomide, pomalidomide, and selinexor. PI, proteasome inhibitor; RRMM, relapsed or refractory multiple myeloma; SLR, systematic literature review; ITC, indirect treatment comparisons

Fig. 2

OS (A), DoR (B) and PFS (C) Kaplan-Maier plots for belamaf 2.5 mg/kg (DREAMM-2) observed and MAIC adjusted versus sel + dex (STORM Part 2). (D) OS versus SoC from the MAMMOTH study (overlay of the estimates from different sources). Belamaf, belantamab mafodotin; DoR, duration of response; MAIC, matching-adjusted indirect comparison; OS, overall survival; PFS, progression-free survival; sel + dex, selinexor plus dexamethasone

Fig. 3

Breakdown of patients per response type in the belamaf cohort before and after base case population adjustment from DREAMM-2 and in the observed sel + dex cohort from STORM Part 2. Belamaf, belantamab mafodotin; CR, complete response; ORR, overall response rate; OS, overall survival; PR, partial response; sCR, stringent complete response; sel + dex, selinexor plus dexamethasone; VGPR, very good partial response

Fig. 4

Summary of the comparative safety of belamaf versus sel + dex before and after MAIC adjustment using all MAIC models. A Hematologic and B non-hematologic adverse events. ^aIncludes the preferred terms thrombocytopenia, platelet count decreased; ^bincludes the preferred terms lymphopenia, lymphocyte count decreased; ^cincludes the preferred terms fatigue and asthenia. OR < 1 favors belamaf; OR < 0.5, risk 50% lower with belamaf. TEAEs highlighted in gray boxes were significantly different. Belamaf, belantamab mafodotin; CI, confidence interval; MAIC, matching adjusted indirect comparison; sel + dex, selinexor plus dexamethasone; TEAE, treatment-related adverse events