Currently Enrolling Trials
Blenrep (belantamab mafodotin-blmf) is a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate.
Blenrep is specifically indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
Blenrep is supplied as a solution for intravenous injection. The recommended dosage of Blenrep is 2.5 mg/kg of actual body weight given as an intravenous infusion over approximately 30 minutes once every 3 weeks until disease progression or unacceptable toxicity.
Mechanism of Action
Blenrep (belantamab mafodotin-blmf) is an antibody-drug conjugate (ADC). The antibody component is an afucosylated IgG1 directed against BCMA, a protein expressed on normal B lymphocytes and multiple myeloma cells. The small molecule component is MMAF, a microtubule inhibitor. Upon binding to BCMA, belantamab mafodotin-blmf is internalized followed by release of MMAF via proteolytic cleavage. The released MMAF intracellularly disrupts the microtubule network, leading to cell cycle arrest and apoptosis. Belantamab mafodotin-blmf had antitumor activity in multiple myeloma cells and mediated killing of tumor cells through MMAF-induced apoptosis, as well as by tumor cell lysis through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).
Adverse effects associated with the use of Blenrep may include, but are not limited to, the following:
- keratopathy (corneal epithelium change on eye exam)
- decreased visual acuity
- blurred vision
- infusion-related reactions
- grade 3 or 4 laboratory abnormalities including platelets decreased, lymphocytes decreased, hemoglobin decreased, neutrophils decreased, creatinine increased, and gamma-glutamyl transferase increased
The Blenrep drug label comes with the following Black Box Warning: Blenrep caused changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes. Conduct ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms. Withhold Blenrep until improvement and resume, or permanently discontinue, based on severity. Blenrep is available only through a restricted program, called the Blenrep REMS.
Clinical Trial Results
The FDA granted accelerated approval to Blenrep for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
FDA accelerated approval was based on DREAMM-2, an open-label, multicenter study. Eligible patients had relapsed or refractory multiple myeloma, had previously received 3 or more prior therapies, including an anti-CD38 monoclonal antibody, and were refractory to an immunomodulatory agent and a proteasome inhibitor. Patients received either Blenrep 2.5 mg/kg or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. In the DREAMM-2 study, treatment with single-agent Blenrep 2.5 mg/kg every three weeks demonstrated a clinically meaningful overall response rate (ORR) of 31% (97.5%) in patients who had received a median of seven prior lines of treatment (n=97). The median duration of response (DoR) had not been reached at the six-month analysis, but 73% of responders had a DoR equal to or greater than six months.