FDA Requests Belantamab Mafodotin for R/R Multiple Myeloma Be Pulled From US Market


After an update from the phase 3 DREAMM-3 study the use of belantamab monotherapy for previously treated patients with relapsed or refractory multiple myeloma was pulled from US market authorization by request of the FDA.

Drug manufacturer GSK pulls its monotherapy treatment for previously treated adult patients with relapsed or refractory multiple myeloma (RRMM) belantamab mafodotin-blmf (Blenrep) following a request from the FDA, according to a press release from GSK.1

The FDA request to withdraw belantamab’s US marketing authorization is based on the previous results of the open label, randomized phase 3 confirmatory DREAMM-3 trial (NCT04162210) that did not meet the requirements of the FDA’s accelerated approval program. The trial compared belantamab monotherapy to pomalidomide in combination with low dose dexamethasone (PomDex) in RRMM patients who were treated with at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

“We respect the Agency’s approach to the accelerated approval regulations and associated process. Multiple myeloma is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments,” said Sabine Luik, Chief Medical Officer of GSK, in the press release. “We will continue the DREAMM clinical trial program and work with the US FDA on a path forward for this important treatment option for patients with multiple myeloma.”

In the update of the DREAMM-3 trial the primary endpoint of median progression-free survival (PFS) between the two cohorts was longer in the monotherapy group at 11.2 months compared with 7 months in the combination cohort (HR 1.03; 95% CI, 0.72-1.47).2 The ORR was also higher in the belantamab group at 41% vs 36% for patients on PomDex, and belantamab showed a deeper response than PomDex with a 25% very good partial response (VGPR) in the monotherapy group vs 8% in the combination arm.

Other secondary endpoints included duration of response (DOR) and overall survival (OS), but the median DOR was not reached in the belantamab group compared with 8.5 months in the PomDex group, but at 12 months the DOR rates favored patients on belantamab at 76.8% vs 48.4% in the PomDex arm. OS had only achieved a 37.5% overall maturity with median OS being virtually identical between the 2 arms at a median OS of 21.2 months in the belantamab arm and 21.1 months in the PomDex arm (HR 1.14; 95% CI, 0.77, 1.68).

The FDA had originally granted an accelerated approval to belantamab based off the results of the phase 2 DREAMM-2 study that looked at patients either on 2.5-mg/kg or 3.4-mg/kg of belantamab monotherapy.3 However, this approval was contingent on a confirmed clinical benefit in a phase 3 trial and the update of the DREAMM-3 trial did not show to the FDA enough of a benefit nor statistically significant result.

The original results of the DREAMM-2 study were presented at the 2020 ASCO meeting showed that at 13 month follow up among 31 of the 97 patients on 2.5-mg/kg of belantamab there was an overall response rate (ORR) of 32% (97.5% CI, 21.7-43.6) compared with a 35% ORR in 35 of the 99 patients on 3.4-mg/kg of belantamab (97.5% CI, 23.9-46.0).4 In both the 2.5-mg/kg group and 3.4-mg/kg group VGPR was observed at 58% compared with 66%, respectively.

Safety and tolerability in the phase 3 trial was consistent with previous safety and tolerability results show with belantamab and no new safety signals were observed in this study. In the phase 2 trial adverse events (AEs) of any grade occurred in most patients in both cohorts with treatment-related AEs happening in 88% of patients in the 2.5-mg/kg cohort vs 95% in the 3.5-mg.kg cohort. The most common grade 3 or higher AEs in all patients were keratopathy in 46% of the 2.5-mg/kg cohort and 42% in the 3.4-mg/kg cohort, anemia in 21% and 27%, thrombocytopenia in 22% and 32%, lymphocyte count decreased in 13% and 7%, and neutropenia in 11% and 7%, respectively.

“GSK continues to believe, based on the totality of data available from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) development program, that the benefit-risk profile of belantamab mafodotin remains favorable in this hard-to-treat RRMM patient population,” wrote the company in their press release.

GSK stated that patients currently on belantamab and enrolled in the Blenrep Risk Evaluation and Mitigation Strategy program will have the option to enroll in a further compassionate use program to continue using the monotherapy. Moreover, they are notifying patients currently on belantamab that they should consult their healthcare provider.

Trials are still ongoing with the monotherapy including the DREAMM-7 and DREAMM-8 studies that are looking to evaluate the efficacy of belantamab in combination with bortezomib and dexamethasone vs daratumumab in combination with bortezomib and dexamethasone and belantamab in combination with pomalidomide and dexamethasone compared with that of a combination of pomalidomide, bortezomib and dexamethasone, respectively.  


1. GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorization. News Release. GlaxoSmithKline plc. November 22, 2022. Accessed: November 22, 2022. https://bit.ly/3EwodY1

2. GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma. News release. GlaxoSmithKline plc. November 7th, 2022. Accessed: November 22, 2022. https://bit.ly/3gwmjib

3. FDA approves GSK’s BLENREP (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma. News release. GlaxoSmithKline plc. August 5, 2020. Accessed: November 22, 2022. https://bit.ly/31uAclA

4. Lonial S, Lee HC, Badros A, et al. Pivotal DREAMM-2 study: single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs). Data presented as part of 2020 American Society of Clinical Oncology Virtual Scientific Program; May 29-31, 2020. Abstract 8536.

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