Blenrep (belantamab mafodotin-blmf) produced sustained clinically meaningful responses and improved overall survival in patients with relapsed or refractory multiple myeloma, according to findings from the DREAMM-7 clinical trial.
About Blenrep (belantamab mafodotin)
Blenrep is a monoclonal antibody-drug conjugate, a type of precision cancer medicine that directly targets a B-cell maturation antigen (BCMA) a protein on the surface on myeloma cells. The normal function of BCMA is to promote plasma cell survival and it has been shown to also be important for myeloma cell growth and survival. Blocking the BCMA antigen leads to diminished myeloma cell growth. Upon administration Blenrep selectively binds to BCMA on myeloma cell surfaces. Upon internalization it then binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces tumor cell apoptosis.
Blenrep in combination with bortezomib (Velcade) and dexamethasone (BVd) significantly improved overall survival (OS) over daratumumab (Darzalex) plus bortezomib and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma, according to updated data from the phase 3 DREAMM-7 trial (NCT04246047) presented during the 2024 ASH Annual Meeting and Exposition.3
About DREAMM-7
The randomized, open-label, phase 3 DREAMM-7 clinical trial enrolled patients with multiple myeloma who were at least 18 years of age and received at least 1 prior line of therapy and experienced documented progressive disease after their most recent line. Patients could not have previous exposure to anti-BCMA therapy, nor could they have disease that was refractory to or intolerant of daratumumab or bortezomib.
Participants were randomly assigned to receive belantamab mafodotin at a dose of 2.5 mg/kg intravenously every 3 weeks paired with bortezomib and dexamethasone vs daratumumab at a dose of 16 mg/kg IV weekly for cycles 1 to 3 and then every 3 weeks for cycles 4 to 8. For cycles 9 and later, those in the investigative and control arms received single-agent belantamab mafodotin at 2.5 mg/kg IV every 3 weeks or daratumumab monotherapy at 16 mg/kg IV every 4 weeks, respectively.
The objective response rate (ORR) with BVd was 83% and 71% with DVd. The median duration of response with BVd was more than double that achieved with DVd, at 40.8 months and 17.8 months respectively. At a median follow-up of 39.4 months the median OS was not reached in both the BVd (n = 243 and DVd treatment groups. The predicted median OS is 84 months with BVd compared to 51 months with DVd. The 36-month survival rates in the respective arms were 74% and 60%.
“BVd demonstrated an early, sustained and statistically significant survival benefit in a head-to-head trial against the daratumumab combination,” Vania Hungria, MD, PhD, of Clinica Sao Germano, in Sao Paulo Brazil, said in a presentation of the data. “these results further support the use of BVd as a potential new standard of care in relapsed or refractory multiple myeloma.”
“Side effects were consistent with the known safety profile for the individual agents in each regimen,” Hungria noted. “Although the BVd arm had numerically higher overall rates of grade 3 or 4 and serious AEs, when adjusting for total treatment exposure, safety results were generally comparable between arms. There were more deaths due to myeloma in the DVd vs the BVd arm.”
Treatment was generally well tolerated with the most common side effects being low blood counts however the researchers did report keratopathy – a type of corneal inflammation in the eye also occurred but did not go into detail regarding this potentially significant side effect.
Eye Toxicity
It is concerning that more than 70% of patients treated with either of two doses of Blenrep in the early trials developed keratopathy or changes to the corneal epithelium of the eye, and after 9 months of follow-up, more than half of patients with keratopathy still had the condition according to FDA staff comments in a briefing document prepared for the Oncologic Drugs Advisory Committee (ODAC). Additionally, 21% of patients stopped driving because of vision problems, and 20% either had extreme difficulty reading or gave it up altogether.4-7
In DREAMM-7 bout two-thirds of patients did not have a clinically meaningful drop in best-corrected visual acuity. Nearly all patients with worsening of vision to 20/50 had resolution to normal baseline or improvement of the first event. In the BVd arm, blurred vision was the most frequent ocular side effect experienced; 68% experienced some degree. Ten percent of patients discontinued due to an ocular event.
Blenrep is available through participation in the BLENREP Risk Evaluation and Mitigation Strategy (REMS), which was developed to ensure appropriate use of the medicine. The programme requires education for all physicians prescribing BLENREP and their patients regarding the ocular risks associated with treatment as well as monitoring. Additional information about the BLENREP REMS can be found at www.blenreprems.com or 1-855-209-9188.
References
- 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).
- FDA approves GSK’s BLENREP (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma
- Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma: overall survival analysis and updated efficacy outcomes of the phase 3 DREAMM-7 trial. Blood. 2024;144(suppl 1):772. doi:10.1182/blood-2024-200336
- Hungria V, Robak P, Hus M, e al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090
- Mateos M-V, Robak P, Hus M, et al. Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;42(suppl 36):439572. doi:10.1200/JCO.2024.42.36_suppl.439572
- Blenrep combinations accepted for review by the US FDA for the treatment of relapsed/refractory multiple myeloma. News release. GSK. November 25, 2024. Accessed December 9, 2024. https://www.gsk.com/en-gb/media/press-releases/blenrep-combinations-accepted-for-review-by-the-us-fda-for-the-treatment-of-relapsedrefractory-multiple-myeloma/
