Phase 3 DREAMM-3 Trial Misses PFS End Point for Belantamab Mafodotin in R/R Multiple Myeloma

The phase 3 DREAMM-3 trial (NCT04162210) assessing belantamab mafodotin-blmf (Blenrep) vs pomalidomide (Pomalyst) plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma did not meet its primary end point of progression-free survival (PFS), according to a press release from GSK.¹

The median PFS was 11.2 months in the belantamab arm vs 7 months in the pomalidomide arm (HR, 1.03; 95% CI, 0.72-1.47). The overall response rate (ORR) was 41% in the belantamab arm vs 36% in the pomalidomide arm, with 25% having a very good partial response or better vs 8%, respectively. In the belantamab arm, the median follow-up was 11.5 months vs 10.8 months in the pomalidomide arm, the duration of response was not reached in either arm; the 12-month DOR rates were 76.8% vs 48.4%, respectively.

A total of 325 patients were randomized 2:1 in the open-label trial. Secondary end points included overall survival (OS), ORR, clinical benefit rate, and DOR. Patients received either 2.5 mg/kg of belantamab or pomalidomide plus dexamethasone every 3 weeks on days 1 to 21 of each 28-day cycle. Dexamethasone was given on days 1, 8, 15, and 22 of each cycle.

At the time of the primary analysis, OS had reached 37.5% of overall maturity. In the belantamab arm, the median OS was 21.2 months vs 21.1 months in the pomalidomide arm (HR, 1.14; 95% CI, 0.77-1.68).

Patients with an ECOG performance status of 0 to 2, histologically or cytologically confirmed disease, and measurable disease were included in the trial. Patients who underwent prior autologous stem cell transplant, had adequate organ function, and experienced prior treatment-related toxicities of grade 1 or less at the time of enrollment—except for grade 2 peripheral neuropathy—were also included.

Those who had symptomatic amyloidosis, active POEMS (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), and active plasma cell leukemia were excluded. Additional exclusion criteria included having anti-myeloma therapy within 14 days or less of treatment, receiving a prior anti-multiple myeloma antibody within 30 days of treatment, or prior B-cell maturation antigen-targeted therapy. If the patient had major surgery within 4 weeks of treatment, an active renal condition, serious or unstable preexisting medical conditions, or a history of pneumonitis they were excluded.

In August 2020, belantamab mafodotin monotherapy was given accelerated approval by the FDA for patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.² The approval was based on the phase 2 DREAMM-2 trial (NCT03525678), which assessed the agent in those with myeloma who progressed following treatment with an anti-CD38 antibody. Patients had an ORR of 31% (95% CI, 21%-43%), with 73% of responders having a response lasting 6 months or more.

Belantamab mafodotin is continuing to be evaluated in the phase 3 DREAMM-7 trial (NCT04246047) in combination with bortezomib (Velcade) and dexamethasone and the phase 3 DREAMM-8 trial (NCT04484623) in combination with pomalidomide and dexamethasone.

References

1. GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma. News release. GSK. November 7, 2022. Accessed November 8, 2022. https://bit.ly/3FYNEnB
2. FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. News release. FDA. August 5, 2020. Accessed November 8, 2022. https://bit.ly/3hsnUFF