Belantamab Mafodotin Plus Vd Earns Breakthrough Therapy Designation in China for R/R Myeloma

Hesham Abdullah, MD

The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted breakthrough therapy designation (BTD) for belantamab mafodotin-blmf (Blenrep) in combination with bortezomib (Velcade) plus dexamethasone (Vd) for the treatment of patients with relapsed/refractory multiple myeloma.¹

The designation was based on data from the phase 3 DREAMM-7 trial (NCT04246047), which showed that at a median follow-up of 28.2 months (range, 0.1 to 40.0), patients treated with belantamab mafodotin plus Vd (n = 243) achieved a median progression-free survival (PFS) of 36.6 months (95% CI, 28.4–not reached [NR]) compared with 13.4 months (95% CI, 11.1-17.5) for those treated with daratumumab (Darzalex) plus Vd (DVd; n = 251; HR, 0.41; 95% CI, 0.31-0.53; P < .001).²

The 18-month overall survival (OS) rates were 84% for the belantamab mafodotin group vs 73% for the DVd group.2 A trend favoring OS was observed in the experimental arm but did not reach statistical significance at the time of the trial’s interim analysis; OS follow-up is still ongoing.¹

“Breakthrough therapy designation in China underscores the potential for [belantamab mafodotin] to redefine outcomes for patients with multiple myeloma at or after their first relapse,” Hesham Abdullah, senior vice president, global head oncology, R&D, at GSK, stated in a news release. “We look forward to continuing to work with the health authority in China and others worldwide to bring [belantamab mafodotin–based] combinations to patients as expeditiously as possible.”

DREAMM-7 was a multicenter, open-label, randomized trial that enrolled patients at least 18 years of age with a confirmed diagnosis of multiple myeloma who were previously treated with at least 1 prior line of therapy. Documented disease progression during or after the most recent therapy was required. Other key inclusion criteria consisted of an ECOG performance status of 0 to 2; at least 1 aspect of measurable disease; resolution of all prior treatment-related toxicities to grade 1 or lower at the time of enrollment, except for alopecia; and adequate organ function.³

Patients were excluded if they were intolerant to daratumumab; refractory to daratumumab or any other anti-CD38 monoclonal antibody; intolerant or refractory to bortezomib; had ongoing grade 2 or higher peripheral neuropathy or neuropathic pain; received prior treatment with BCMA-targeted therapy; or underwent prior allogenic stem cell transplant.

Patients were randomly assigned to receive belantamab mafodotin plus Vd or DVd.3 Belantamab mafodotin was administered at 2.5mg/kg once every three weeks.¹

PFS served as the trial’s primary end point. Secondary end points included complete response (CR) rate, overall response rate, clinical benefit rate, duration of response, time to response, time to progression, OS, time to second progression, minimal residual disease (MRD)–negativity rate, and safety.³

Additional data showed that 25% of the patients in the belantamab mafodotin group experienced a CR or better and achieved MRD negativity compared with 10% of those in the DVd arm.²

Regarding safety, grade 3 or higher adverse effects (AEs) were reported in 95% of the patients in the belantamab mafodotin group vs 78% of those in the DVd group. The rates of ocular AEs were 79% in the experimental arm vs 29% in the control arm. Ocular toxicities were managed with dose modifications, and most AEs of worsening visual acuity resolved.

References

1. Blenrep (belantamab mafodotin) in combination receives breakthrough therapy designation in China for treatment of relapsed/refractory multiple myeloma. News release. GSK. September 13, 2024. Accessed September 16, 2024. https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-in-combination-receives-breakthrough-therapy-designation-in-china-for-treatment-of-relapsedrefractory-multiple-myeloma/
2. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090
3. Evaluation of efficacy and safety of belantamab mafodotin, bortezomib and dexamethasone versus daratumumab, bortezomib and dexamethasone in participants with relapsed/​refractory multiple myeloma (DREAMM 7). ClinicalTrials.gov. Updated December 13, 2023. Accessed September 16, 2024. https://www.clinicaltrials.gov/study/NCT04246047