Abstract Background: In the ongoing global, open-label, randomized phase 3 DREAMM-7 study (NCT04246047), belantamab mafodotin, bortezomib, and dexamethasone (BVd) demonstrated significant and clinically meaningful progression-free survival (PFS) benefit (median follow-up, 28.2 months; hazard ratio HR, 0.41; 95% CI, 0.31-0.53; P0.001), as well as early and sustained overall survival (OS) benefit (median follow-up, 39.4 months; HR, 0.58; 95% CI, 0.43-0.79; P=0.0002), vs daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM) who received ≥1 prior line of therapy. With other emerging, heterogenous treatment options for RRMM, critical assessment of the comparative efficacy of BVd vs alternative therapies is warranted to inform clinical practice and health policy decisions. However, the relapsing nature of multiple myeloma (MM) leads to limited follow-up time in randomized clinical trials and challenges in estimating long-term OS. Therefore, we estimated the expected long-term OS/life-years (LYs) and quality-adjusted LYs (QALYs) over the lifetime of patients treated with BVd compared with other alternative therapies for MM at first relapse. Methods: To evaluate BVd vs proteasome inhibitor–based alternative therapies, a de novo partitioned survival model was developed with the health states progression-free disease, progressed disease, and death; the starting age of patients in the model was 64 years, and a time horizon of 36 years was used to estimate lifetime LYs and QALYs. For overall LYs, efficacy data for BVd and DVd were sourced from DREAMM-7, while relative treatment effects of nontrial alternative therapies were informed by a published network meta-analysis. Parametric survival models were used to extrapolate PFS and OS for BVd and DVd; clinicians were asked to estimate the OS for BVd and DVd at 5, 10, and 15 years following treatment initiation, to validate the long-term survival extrapolation and ensure alignment with clinical expectations. HRs were applied to the DVd OS curve to estimate PFS and OS for the nontrial alternative therapies. To estimate QALYs for each treatment, health state utilities were informed by DREAMM-7 EQ-5D-3L data and adjusted for adverse event (AE) disutilities; the proportion of patients with grade ≥3 AEs based on trial data was used to calculate the disutilities for each alternative therapy. Results: BVd led to more LYs (12.0) and QALYs (9.8) compared with all alternative therapies (carfilzomib and dexamethasone Kd, 8.1 and 6.6, respectively; daratumumab and Kd DKd, 10.1 and 8.2; isatuximab and Kd IsaKd, 10.1 and 8.2; bortezomib and dexamethasone Vd, 6.0 and 4.9; pomalidomide and Vd, 8.1 and 6.6; selinexor and Vd, 7.3 and 5.9; DVd, 8.8 and 7.2). Estimated probability of survival at 5 years using the model was higher for BVd (64%) vs all alternative therapies (range, 34% Vd to 53% DKd and IsaKd). Conclusions: BVd led to substantially more LYs and QALYs compared with alternative treatment regimens for RRMM, highlighting the potential of BVd to extend survival and enhance clinical and quality-of-life benefits for these patients. These insights are critical to support clinical and health policy decision-making in MM at first relapse, supporting the use of BVd as a standard of care in this population. Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Suvannasankha et al. (Mon,) studied this question.