DREAMM-6: Safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (RRMM).

Abstract

8502 Background: Belantamab mafodotin, a B-cell maturation antigen targeting immunoconjugate, demonstrated clinically meaningful, single-agent activity in patients with heavily pre-treated RRMM refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody (DREAMM-2, NCT03525678, Lancet Oncol.2020). The multimodal mechanism of action and manageable safety profile make belantamab mafodotin a promising candidate for use in different RRMM combination regimens. Methods: DREAMM-6 (NCT03544281) is an ongoing, two-part, two-arm, study evaluating the safety, tolerability, and clinical activity of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) and lenalidomide/dexamethasone in patients previously treated with ≥1 prior therapy line. Here, we present data for belantamab mafodotin in combination with BorDex. Part 1 (dose escalation) and Part 2 (dose expansion) evaluated belantamab mafodotin (2.5 and 3.4 mg/kg) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) in combination with BorDex. Results: As of February 6, 2020, 52 patients were enrolled: 6 patients were enrolled at 2.5 mg/kg single dose and 7 at 3.4 mg/kg single dosing in Part 1, and 45 patients in Part 2. No dose-limiting toxicities were observed. Corneal events (including keratopathy, blurred vision, and dry eye) and thrombocytopenia were the most frequently reported AEs and were clinically manageable. Conclusions: In DREAMM-6, preliminary data demonstrate that the combination of belantamab mafodotin and BorDex has an acceptable safety profile, with no new safety signals identified. Funding: GlaxoSmithKline (207497). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281 .

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

“…A trial evaluating the addition of belamaf to standard MM backbone treatments (Rd and Vd) is ongoing in RRMM (DREAMM-6). Recently, data about the first 18 patients treated with belamaf-Vd were presented [43]. Efficacy was good, with a high ORR (78%).…”

Monoclonal and Bispecific Anti-BCMA Antibodies in Multiple Myeloma

“…The combination with Pembrolizumab does not seem to add toxicity during treatment; in the DREAMM-4 study, the main AEs were keratopathy, fatigue and anemia [50].…”

“…13 patients have been enrolled so far. The combination showed clinical activity, with an ORR of 67% in the 2.5 mg/kg arm and of 14% in the 3.4 mg/kg arm [50]. Available results of the clinical trials with Belantamab Mafodotin are summarized in Table 1.…”

Emerging immunotherapies in multiple myeloma

“…Preliminary results for another study with 18 patients treated on the belantamab, bortezomib, and dexamethasone arm was presented recently, with an overall response rate of 78%; however, all 18 patients developed grade 13 keratopathy. 113 This visual toxicity is a unique but potentially serious side effect to this drug that needs close monitoring with an ophthalmologist. Another antibody drug conjugate, DFRF4539A, is an antiFcRH5 (also known as FcRL5) antibody conjugated to monomethyl auristatin and has shown limited activity and high incidence of toxicity in a phase I study; therefore, it was unsuccessful for this disease (table 2) .…”