Belantamab mafodotin + Vd more than doubles PFS in relapsed/refractory multiple myeloma

(NCT04246047) that were presented during the 2024 February ASCO Plenary Series.

The median PFS with BVd (n = 243) was 36.6 months (95% CI, 28.4-not reached [NR]) vs 13.4 months (95% CI, 11.1-17.5) with DVd (n = 251), translating to a 59% reduction in the risk of disease progression or death (HR, 0.41; 95% CI, 0.31-0.53; P <.00001). the 18-month pfs rates were 69% and 43% with bvd and dvd, respectively. moreover, pfs was improved across all prespecified subgroups, including patients who were refractory to lenalidomide ([revlimid] n="79;" hr, 0.37; 95% ci, 0.24-0.56) and those with high-risk cytogenetics (hr, 0.36; 95% ci, 0.22-0.58). notably, bvd also doubled the rates of complete response (cr) or better (34.6% vs 17.1% with bvd and dvd, respectively), minimal residual disease (mrd) negativity in those responders (24.7% [95% ci, 19.4%-30.6%] vs 9.6% [95% ci, 6.2%-13.9%]), and median duration of response (dor; 35.6 months [95% ci, 30.5-nr] vs 17.8 months [95% ci, 13.8-23.6]).

“These results suggest that BVd can potentially be a new standard of care in second-line or later relapsed/refractory multiple myeloma owing to the robust efficacy, manageable safety, and ease of administration,” lead study author Maria-Victoria Mateos, PhD, of the Hospital Universitario de Salamanca, in Spain, said in a presentation of the data.

Belantamab mafodotin is a humanized, afucosylated anti-BCMA monoclonal antibody conjugated to the microtubule inhibitor monomethyl auristatin-F, by a protease-resistant cysteine linker. The agent enhances immune response through antibody-drug conjugate–mediated apoptosis, antibody-dependent cell-mediated toxicity, and antibody-dependent cellular phagocytosis, representing an attractive treatment for patients who relapse on first-line triplet or quadruplet therapy.

In November 2022, GSK initiated the process to withdraw the US marketing authorization for belantamab mafodotin in adult patients with relapsed/refractory multiple myeloma who previously received at least 4 therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The decision to withdraw the indication was based on a FDA request following data from the phase III DREAMM-3 trial (NCT04162210), which indicated that belantamab mafodotin did not improve PFS over pomalidomide (Pomalyst) and low-dose dexamethasone.

In September 2023, the European Medicines Agency’s Committee for Medicinal Produces for Human Use recommended against the renewal of the conditional marketing authorization for belantamab mafodotin for patients with relapsed/refractory multiple myeloma who had received at least 4 prior therapies. Comparative data for the agent had not been available at the time that the European Commission approved the agent in August 2020,7 and DREAMM-3 did not meet its primary end point.