NEWS & PERPECTIVE

Belantamab mafodotin-blmf: a potential new candidate in combination treatment for patients with relapsed or refractory multiple myeloma

29 Oct 2020

In the recent DREAMM-2 study, single-agent belantamab mafodotin-blmf has demonstrated anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma.1 Based on this result, the United States Food and Drug Administration (US FDA) has granted accelerated approval to belantamab mafodotin-blmf for adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including anti-CD38 monoclonal antibody, proteasome inhibitor, and immunomodulatory agent.2

Generally considered treatable but not curable, multiple myeloma is a cancer of the bone marrow and is the second most common blood cancer in the US.3 Despite numerous therapeutic advances, treatment of patients with relapsed or refractory multiple myeloma remains challenging.1 In particular, patients with disease refractory to anti-CD38 monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents have a poor prognosis and are in need of an effective alternative when currently available therapeutic options are exhausted.1

To further evaluate the safety and effectiveness of belantamab mafodotinblmf as an alternative therapeutic option for patients with relapsed or refractory multiple myeloma, the open-label, two-arm, phase 2 DREAMM-2 study was conducted across 58 multiple myeloma specialty centres in eight countries.1 Patients aged ­≥18 years with relapsed or refractory multiple myeloma, with disease progression after three or more lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory and/or intolerant to an anti-CD38 monoclonal antibody with an Eastern Cooperative Oncology Group performance status of 0-2 were recruited.1 Patients were centrally randomly assigned (1:1) with permuted blocks, and stratified by previous lines of therapy (≤4 vs. >4) and cytogenetic features to receive either 2.5mg/kg or 3.4mg/kg belantamab mafodotin-blmf via intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity.1

In the study, 293 patients were screened and 196 were included in the intention-to-treat population (97 in the 2.5mg/kg cohort and 99 in the 3.4mg/kg cohort). On the primary analysis data cut-off date, 31% (97.5% CI: 20.8-42.6) and 34% (97.5% CI: 23.9-46.0) of patients in the 2.5mg/kg and the 3.4mg/kg cohorts, respectively, achieved an overall response.1 Additionally, approximately 20% of patients from both cohorts achieved a very good partial or better response. The depth and durability of responses seen with single agent belantamab mafodotin-blmf were comparable favorably with the responses described with other approved combination treatments for relapsed or refractory multiple myeloma.1

The most commonly reported adverse events in patients receiving belantamab mafodotin-blmf were keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue which were mostly reversible and manageable with dose modifications and close monitoring.2,4 However, due to these possible side effects, belantamab mafodotin-blmf is only currently available through a restricted program under the Risk Evaluation and Mitigation Strategy (REMS) with a recommended intravenous dosage of 2.5mg/kg.2 That said, the European Medicines Agency has also considered the benefits of belantamab mafodotin-blmf to outweigh its risks and has granted the agent conditional authorization that is dependent on further evidence for approval.4

With an alternative mechanism of action and manageable safety profile, belantamab mafodotin-blmf is a potential candidate in combination treatment regimens for patients with relapsed or refractory multiple myeloma.1 Having demonstrated an anti myeloma activity in patients with relapsed or refractory multiple myeloma, in particular for those with heavily pre-treated disease refractory to a proteasome inhibitor and immunomodulatory drug, and refractory or/and intolerant to an anti CD38 monoclonal antibody, belantamab mafodotin-blmf in combination with standard of care or novel agents could fill the current unmet need in the treatment landscape of relapsed or refractory multiple myeloma.


References
  1. Lonial S et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. The Lancet Oncology. 2020;21(2):207-221
  2. Food and Drug Administration. FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma. Accessed September 25, 2020.
  3. Drugs.com. GSK Announces FDA Advisory Committee Meeting to Review Belantamab Mafodotin for the Treatment of Patients with Relapsed/Refractory Multiple Myeloma. https://www.drugs.com/clinical_trials/gsk-announces-fda-advisory-committee-meeting-review-belantamab-mafodotin-patients-relapsed-18666.html. Accessed September 25, 2020.
  4. European Medicines Agency. Blenrep. https://www.ema.europa.eu/en/medicines/human/EPAR/blenrep. Accessed September 25, 2020.
BELANTAMAB MAFODOTIN-BLMF
MULTIPLE MYELOMA
DREAMM-2 STUDY