Research Continues Evaluating Belantamab Mafodotin in Relapsed/Refractory Multiple Myeloma

Belantamab mafodotin (Blenrep, GSK) monotherapy did not meet the primary endpoint of progression-free survival (PFS) compared with pomalidomide in combination with low dose dexamethasone (PomDex) in patients with relapsed or refractory multiple myeloma (RRMM). These findings were reported in the phase 3 open-label, randomized, DREAMM-3 trial.

Belantamab mafodotin-blmf is a first-in-class, anti-B-cell maturation antigen(BCMA) therapy indicated for adults with RRMM who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. This indication was approved by the FDA on August 5, 2020, under an accelerated approval based on the response rate.

The antibody component is an afucosylated IgG1 directed against BCMA, a protein expressed on normal B lymphocytes and multiple myeloma cells. The small molecule component is MMAF, a microtubule inhibitor. Upon binding to BCMA, belantamab mafodotin-blmf is internalized, followed by release of MMAF via proteolytic cleavage. The released MMAF intracellularly disrupts the microtubule network, leading to cell cycle arrest and apoptosis.

The drug has shown antitumor activity in multiple myeloma cells and mediated killing of tumor cells through MMAF-induced apoptosis, as well as by tumor cell lysis through antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.

In the DREAMM-3 trial, 325 participants were randomized 2:1 to receive either single agent belantamab mafodotin administered as a 2.5 mg/kg dose every 3 weeks or pomalidomide in combination with low dose dexamethasone. Pomalidomide was administered daily on days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (days 1, 8, 15, and 22 of each cycle). The primary endpoint was PFS, with secondary endpoints that included safety, overall survival (OS), overall response rate (ORR), duration of response (DOR), and assessment of minimal residual disease.

The observed median PFS was longer for belantamab mafodotin versus pomalidomide in combination with low dose dexamethasone. The median follow-up was 11.5 months for belantamab mafodotin and 10.8 months for pomalidomide in combination with low dose dexamethasone. The median DOR was not reached for belantamab mafodotin compared with 8.5 months for pomalidomide in combination with low dose dexamethasone. DOR rates at 12 moths were 76.8% and 48.4% for belantamab mafodotin and pomalidomide in combination with low dose dexamethasone, respectively.

The safety and tolerability profile of belanatamab mafodotin was consistent with the known safety profile, and no new safety signals were identified. In the DREAMM-2 trial, the most common adverse effect associated with belanatamab mafodotin was keratopathy, based on corneal exam findings.

Adverse reactions that required dose reductions occurred in 29% of patients in the DREAMM-2 trial. Dose reductions occurred in greater than 3% of patients with adverse reactions that included keratopathy (23%) and thrombocytopenia (5%). Other adverse effects consisted of infusion-related reactions, gastrointestinal disorders (nausea, constipation, and diarrhea), pyrexia, and fatigue.

Additional trials within the DREAMM clinical trial program will continue. These trials are designed to demonstrate the benefit of belantamab mafodotin in combination with novel therapies and standard-of-care treatments in earlier lines of therapy and dosing optimization to maintain efficacy while reducing corneal events.

REFERENCE

GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma. GSK. November 7, 2022. Accessed November 7, 2022. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-dreamm-3-phase-iii-trial-for-blenrep/