Longer term outcomes with single‐agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13‐month follow‐up from the pivotal DREAMM‐2 study

Abstract

BACKGROUND:On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg. METHODS: DREAMM-2 is an ongoing, phase 2, open-label, 2-arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti-CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee. RESULTS: As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty-one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%-43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression-free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6-3.6 months), respectively. Response and survival outcomes in patients who had high-risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow-up. CONCLUSIONS: Extended follow-up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM. Cancer 2021;0:1-15.

“Real-life” data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma—the Mayo Clinic experience

“…In the DREAMM-2 trial, 100% of the patients were triple refractory, as in our cohort. The ORR in the DREAMM-2 was 31% and the mPFS 2.8 months [ 12 ]. Table 2 compares our cohort to the DREAMM-2 cohort 2.5 mg/kg in terms of patient characteristics and outcomes.…”

“…The ORR was 30% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort. In the recently published 13-month follow-up, the median overall survival (OS) was 13.7 months and the median PFS was 2.8 months [ 12 ]. As a result, in August 2020, the drug was approved by the Food and Drug Administration (FDA) as monotherapy for use in RRMM patients that have previously received four or more lines of therapy.…”

“…Belantamab is associated with adverse effects typically seen with other myeloma therapies (such as thrombocytopenia, anemia, and infusion-related reactions) [ 12 ], but also with a unique adverse effect of ocular toxicity [ 13 , 14 ]. Grade 3–4 keratopathy (e.g., corneal epithelium changes) was reported in 46% of the DREAMM-2 cohort [ 12 ]. Keratopathy led to treatment discontinuation, dose reductions, and dose delays in 4%, 50%, and 95% of the DREAMM-2 cohort, respectively.…”

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

“…Regarding this limit, MMAF ADCs require high tumor expression of target antigen [42]. Nevertheless, a MMAF-conjugated ADC, belantamab mafodotin, was approved in 2020 by the FDA and the EMA for relapsed or refractory multiple myeloma treatment [43,44].…”

Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States

“…[12][13][14] The responses reported with belamaf 2.5 mg/kg once every 3 weeks in the primary analysis of the DREAMM-2 study (median follow-up: 6.3 months; overall response rate [ORR]: 31%) 13 were sustained at 13 months; the ORR was 32% with an estimated median duration of response of 11.0 months, median OS of 13.7 months, and median progression-free survival (PFS) of 2.8 months. 15 While clinical outcomes have improved with the introduction of newer drug therapies for RRMM in recent years, prolonged survival increases the likelihood of receiving multiple lines of therapy. 16 Additionally, managing RRMM remains a high patient-and economiccost burden.…”