Matching-adjusted indirect comparison (MAIC) for belantamab mafodotin (belamaf) with pomalidomide and dexamethasone (BPd) vs daratumumab with pomalidomide and dexamethasone (DPd) in relapsed/refractory multiple myeloma (RRMM).

Abstract

e19574 Background: BPd is approved for patients (pts) with RRMM in multiple countries based on results of the phase 3 DREAMM-8 trial. DREAMM-8 evaluated BPd vs pomalidomide with bortezomib and dexamethasone, allowing enrollment of pts previously treated with daratumumab. To support clinical decision-making in the absence of head-to-head comparison, a MAIC was performed to estimate the relative clinical efficacy of BPd vs DPd in pts with RRMM who received ≥1 prior therapy line (2L+), including lenalidomide (len). Methods: A systematic literature review was undertaken and updated as of January 2024 to identify efficacy/safety data in 2L+ RRMM, and studies were assessed for common treatment arms and pt characteristics. MAICs of progression-free survival (PFS) and minimal residual disease negativity (MRD-) were conducted using the len-exposed populations from phase 3 trials of BPd (DREAMM-8) and DPd (APOLLO). As these trials lack a common comparator arm, an unanchored approach was required. Individual pt data (IPD) were available for BPd-treated pts (n=155) from DREAMM-8, while only published summary data were available for DPd-treated pts (n=151) from APOLLO. BPd-treated pts from DREAMM-8 were weighted (using IPD) to match DPd-treated pts from APOLLO in terms of age (<75 , ≥75 years), prior lines of therapy (LOT; 1, 2–3, ≥4), refractoriness to len/immunomodulatory drugs (IMD; yes, no), refractoriness to proteasome inhibitors (PI; yes, no), International Staging System (ISS) stage (1/2, 3), cytogenetic risk (standard, high), Eastern Cooperative Oncology Group performance status (ECOG PS; 0, 1, 2), and creatinine clearance (CrCl; ≤60, >60 mL/min). Outcomes for weighted BPd-treated pts were compared to those for DPd-treated pts. DREAMM-8 interim analysis 1 (MRD-) and 3 (PFS) data were used for analysis. Cox regression and logistic regression were performed for PFS and MRD- comparisons, respectively. Results: After matching, equal proportions in both arms were: ≥75 years (17%); had 2–3 prior LOT (75%); were refractory to an IMD (79%) or PI (47%); had ISS stage 3 (22%); ECOG PS of 1 (36%); had CrCl ≤60 mL/min (26%); and had high cytogenetic risk (38%). Effective sample size of weighted BPd-treated pts was 65.6. PFS favored BPd, with medians of 18.1 vs 12.4 months (hazard ratio 0.74 [95% confidence interval 0.50, 1.09]). MRD- also favored BPd, with rates of 25.8% vs 8.6% (odds ratio 2.73 [95% confidence interval 1.26, 5.92]). Only MRD- was statistically significant. Conclusions: While MAICs have inherent limitations, BPd demonstrated improved relative clinical efficacy vs DPd when adjusting for differences in key baseline pt characteristics. These findings demonstrate the importance and utility of BPd in the 2L+ RRMM setting with the growing use of len with daratumumab in early LOT.