FDA Approves Belantamab Mafodotin-blmf for Relapsed/Refractory Multiple Myeloma

The FDA has approved belantamab mafodotin-blmf (Blenrep) as a treatment for patients with relapsed/refractory multiple myeloma who have received 4 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor, and an anti-CD38 antibody.¹

The approval is based on findings from the pivotal DREAMM-2 trial, which showed that belantamab mafodotin elicited an overall response rate (ORR) of 31% (97.5% CI, 20.8-42.6) in patients with relapsed/refractory multiple myeloma who received the treatment at the recommended 2.5 mg/kg dose.² In patients who received belantamab mafodotin at 3.4 mg/kg, the ORR was 34% (97.5% CI; 23.9-46.0); both ORRs were assessed by an independent review committee (IRC).

“While treatable, refractory multiple myeloma is a significant clinical challenge with poor outcomes for patients whose disease has become resistant to the current standard of care," lead DREAMM-2 investigator Sagar Lonial, MD, chief medical officer, Winship Cancer Institute of Emory University in Atlanta, Georgia, chair of Emory Department of Hematology and Medical Oncology, stated in a press release.

"Due to the limited options currently available, these patients are often retreated with drugs from the same classes after they relapse, which is why the approval of BLENREP, the first anti-BCMA therapy, is significant for both patients and physicians alike.”

In the open-label, 2-arm, phase II DREAMM-2 trial, investigators accrued 196 patients with relapsed/refractory myeloma for the intent-to-treat population between June 18, 2018, and January 2, 2019. Patients were randomized 1:1 to receive belantamab mafodotin at either 2.5 mg/kg (n = 97) or 3.4 mg/kg (n = 99) intravenously every 3 weeks until disease progression or unacceptable toxicity.

To be eligible for enrollment, patients had an ECOG performance status of 0 to 2, experienced disease progression on ≥3 lines of therapy, were refractory to a proteasome inhibitor and an IMiD, and were refractory and/or intolerant to a CD38-directed monoclonal antibody.

Patient characteristics were well balanced between the 2 treatment arms. In the 2.5-mg/kg arm, the median age was 65 years (range, 60-70), 53% were male, and 42% had high-risk cytogenetics. Patients had received a median of 7 (range, 3-21) lines of prior treatment, with 84% of patients having received >4 lines of therapy. Prior therapies included bortezomib (Velcade; 98%), carfilzomib (Kyprolis; 76%), lenalidomide (Revlimid; 100%), pomalidomide (Pomalyst; 92%), daratumumab (Darzalex; 100%), and isatuximab (3%). Additionally, 76% of patients were refractory to bortezomib, 65% were refractory to carfilzomib, 90% were refractory to lenalidomide, 87% were refractory to pomalidomide, 100% were refractory to daratumumab, and 3% of patients were refractory to isatuximab.

The median age in the 3.4-mg/kg arm was 67 years (range, 61-72), 57% were male, and 47% had high-risk cytogenetics. Patients had received a median of 6 (range, 3-21) prior lines of therapy, with 83% having received >4 lines. Prior therapies received included bortezomib (98%), carfilzomib (65%), lenalidomide (100%), pomalidomide (85%), daratumumab (97%), and isatuximab (2%). The rate of the overall cohort refractory to each of these therapies was bortezomib, 75%; carfilzomib, 58%; lenalidomide, 89%; pomalidomide, 78%; daratumumab, 92%; and isatuximab, 1%.

Additional results showed that, the 31% ORR in the 2.5-mg/kg cohort included a very good partial response (VGPR) or better in 18 (19%) patients. Of the 34% ORR in the 3.4 mg/kg arm, a ≥VGPR was achieved in 20 (20%) of patients. There were 3 stringent complete responses or complete responses in each cohort.

The median follow-up was 6.3 months and 6.9 months in the 2.5-mg/kg and 3.4-mg/kg cohorts, respectively. Overall, the median duration of response (DOR) was not reached. At the data cutoff date, 18 patients receiving belantamab mafodotin at 2.5 mg/kg and 25 at the 3.4-mg/kg dose had a DOR of ≥4 months; the authors noted that progression-free survival (PFS) follow-up was ongoing and patients were continuing on treatment.

The median PFS was 2.9 months (95% CI, 2.1-3.7) and 4.9 months (95% CI, 2.3-6.2) in the 2.5-mg/kg and 3.4-mg/kg cohorts, respectively. Overall survival data were immature at the time of the analysis.

For the safety analysis, there were 95 patients in the 2.5-mg/kg arm and all 99 patients in the 3.4-mg/kg arm. The most frequently reported grade 3/4 adverse events (AEs) included keratopathy (27% in the 2.5-mg/kg cohort vs 21% in the 3.4-mg/kg cohort), thrombocytopenia (20% vs 33%, respectively) and anemia (20% vs 25%, respectively). Serious AEs occurred in 40% versus 47% of the 2.5-mg/kg and 3.4-mg/kg cohorts, respectively. Investigators reported 2 patient deaths that were potentially related to treatment: 1 case of sepsis in the 2.5-mg/kg cohort and 1 case of hemophagocytic lymphohistiocytosis in the 3.4-mg/kg group.

Dose delays that were related to AEs occurred in 54% of patients on the 2.5-mg/kg cohort compared with 62% of the 3.4-mg/kg cohort. AE-related dose reductions occurred in 29% versus 41% of the 2 cohorts, respectively. Permanent treatment discontinuation due to AEs occurred in 8% and 10% of patients on the 2.5-mg/kg and 3.4-mg/kg arms, respectively.

The authors noted that 2.5 mg/kg was selected as the recommended dose for future studies with belantamab mafodotin, given the similar efficacy and a more favorable safety profile compared with the 3.4-mg/kg dose.

"As the second most common form of blood cancer in the US, multiple myeloma is an incurable and devastating disease. Blenrep is the first approved anti-BCMA therapy and has the potential to transform the treatment of patients with relapsed or refractory myeloma who have limited treatment options today," Hal Barron, MD, chief scientific officer and president of R&D, GlaxoSmithKline, stated in the press release.

References

1. FDA approves GSK’s BLENREP (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma. News release. Published August 5, 2020. Accessed August 5, 2020. https://bit.ly/3gxEXB1
2. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study [published online December 16, 2019]. Lancet Oncol. https://doi.org/10.1016/S1470-2045(19)30788-0.