CHMP Recommends Against Renewal of Marketing Authorization for Belantamab Mafodotin in R/R Myeloma

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended against renewal of the conditional marketing authorization for belantamab mafodotin-blmf for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 prior treatments.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended against renewal of the conditional marketing authorization for belantamab mafodotin-blmf (Blenrep) for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 prior treatments.1

In August 2020, the European Commission approved belantamab mafodotin for the treatment of adult patients with multiple myeloma who have received at least 4 previous therapies; whose disease is refractory to at least 1 proteasome inhibitor (PI), 1 immunomodulatory agent (IMiD), and 1 anti-CD38 monoclonal antibody; and who have progressed on their last therapy.2

However, comparative data for belantamab mafodotin were not available at the time of its conditional marketing authorization. Subsequent data from the phase 3 DREAMM-3 trial (NCT04162210) showed that patients treated with belantamab mafodotin did not experience a statistically significant improvement in progression-free survival (PFS) compared with those who received pomalidomide (Pomalyst) plus lose-dose dexamethasone (HR, 1.03; 95% CI, 0.72-1.47).3 At a median follow-up of 11.5 months and 10.8 months for the belantamab mafodotin and pomalidomide/ dexamethasone arms, respectively, patients treated with belantamab mafodotin achieved a median PFS of 11.2 months vs 7.0 months for pomalidomide plus dexamethasone.

After DREAMM-3 failed to meet its primary end point, GlaxoSmithKline announced its intention to withdraw the United States marketing authorization for belantamab mafodotin for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a PI, and an IMiD, in November 2022.4

The open-label, randomized DREAMM-3 study enrolled 325 patients at least 18 years of age with histologically or cytologically confirmed relapsed/refractory multiple myeloma who had undergone autologous stem cell transplant (ASCT) or were considered transplant ineligible, and had received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide (Revlimid) and a PI, and must have documented disease progression on, or within 60 days of, completion of the last treatment or must be non-responsive while on last treatment.1,5

Patients also needed to have an ECOG performance status of 0 to 2, adequate organ function, and resolution of all prior treatment-related toxicities to grade 1 or lower, except for alopecia or grade 2 peripheral neuropathy. ASCT was required to have been completed more than 100 days prior to initiating study treatment, and no active infections were permitted.5

The trial excluded patients with symptomatic amyloidosis, active POEMS syndrome, or active plasma cell leukemia; prior treatment with an anti–multiple myeloma monoclonal antibody within 30 days prior to first study treatment; prior BCMA-targeted therapy or prior pomalidomide treatment; prior allogeneic stem cell transplant; or any major surgery within 4 weeks of the start of study treatment.

Patients were randomly assigned 2:1 to receive belantamab mafodotin once every 3 weeks or the combination of pomalidomide on days 1 to 21 of each 28-day cycle and dexamethasone on days 1, 8, 15, and 22 of each cycle.

PFS was the trial’s primary end point. Key secondary end points included overall survival, overall response rate, clinical benefit rate, duration of response, and safety.

References

  1. EMA recommends non-renewal of authorisation of multiple myeloma medicine Blenrep. News release. European Medicines Agency. September 15, 2023. Accessed September 18, 2023. https://www.ema.europa.eu/en/news/ema-recommends-non-renewal-authorisation-multiple-myeloma-medicine-blenrep
  2. European Commission approves Blenrep (belantamab mafodotin) for the treatment of patients with relapsed and refractory multiple myeloma. News release. GlaxoSmithKline, plc. August 26, 2020. Accessed September 18, 2023. https://www.gsk.com/en-gb/media/press-releases/european-commission-approves-blenrep-belantamab-mafodotin-for-the-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma/
  3. GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma. News release. GlaxoSmithKline. November 7, 2022. Accessed September 18, 2023. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-dreamm-3-phase-iii-trial-for-blenrep/
  4. GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorization. News release. GlaxoSmithKline. November 22, 2022. Accessed September 18, 2023. https://us.gsk.com/en-us/media/press-releases/gsk-provides-an-update-on-blenrep-belantamab-mafodotin-blmf-us-marketing-authorization/
  5. Study of single agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone (Pom/Dex) in participants with relapsed/refractory multiple myeloma (RRMM) (DREAMM-3). ClinicalTrials.Gov. Updated September 30, 2022. Accessed September 18, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04162210