Multiple myeloma is a cancer that is created from plasma cells with abnormal genetic variations. Normally, plasma cells grow and divide to make new cells; once cells grown old or get managed, they die. In contrast, myeloma cells replicate throughout the bone marrow, destroy the bone tissue, and crowd-out normal blood cells in the bone marrow as they grow. The antibodies synthesized by myeloma cells do not fight infections like normal antibodies do. Common signs and symptoms include anemia, bone pain, kidney damage due to elevated creatinine or serum protein, infection, fatigue, and hypercalcemia.
Like many types of malignancies, further treatment of multiple myeloma after relapsed, progressive, or refractory disease usually yields a shorter duration and lower quality of response compared to the initial response. There is a high demand for agents that treat multiple myeloma that does not respond or that progresses after first- or subsequent-line therapy.
Belantamab mafodotin-blmf (Blenrep) was approved by the US Food and Drug Administration (FDA) on August 5, 2020 for the treatment of adults 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.
Belantamab mafodotin-blmf (Blenrep) is an anti-BCMA antibody-drug conjugate (ADC) and microtubule inhibitor conjugate that targets B-cell maturation antigen (BCMA), a protein expressed on normal B lymphocytes and multiple myeloma cells. Upon binding to BCMA, belantamab mafodotin-blmf (Blenrep) is internalized and monomethyl auristatin F (MMAF) is released via proteolytic cleavage which causes disruption in the microtubule network and eventually cell cycle arrest and apoptosis. In addition to MMAF-induced apoptosis, belantamab mafodotin-blmf (Blenrep) causes tumor cell lysis through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellula phagocytosis (ADCP). The recommended dosage of belantamab mafodotin-blmf (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.
RISK EVALUATION AND MITIGATION STRATEGY (REMS) PROGRAM
The FDA initiated a Risk Evaluation and Mitigation Strategy (REMS) program due to the risk of ocular toxicity associated with the use of belantamab mafodotin-blmf (Blenrep). This program informs professional providers, individuals receiving this drug, healthcare settings, and wholesalers-distributors about the potential risk and outlines processes to ensure the safety of the individuals receiving this drug. Measures include enrollment/certification into the program, counseling, baseline and follow-up ophthalmic examinations, preservative-free lubricant eye drop use, etc.
The safety and effectiveness of belantamab mafodotin-blmf (Blenrep) was evaluated in DREAMM-2, a Phase 2, open-label, randomized, multicenter, two-arm study. Adult participants had relapsed or refractory multiple myeloma with disease progression after three or more prior therapies, including an anti-CD38 monoclonal antibody, an immunomodulatory agent, and a proteasome inhibitor (median number of prior lines of therapy was 7, range: 3 to 21). Additionally, they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Participants received either belantamab mafodotin-blmf (Blenrep) 2.5 mg/kg or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity (median 3 doses, range 1 to 11). With the focus of this summary on those who received the FDA-approved dose of 2.5 mg/kg, the major efficacy outcome measure of overall response rate was 31% (30 of 97 participants). Ocular adverse reactions occurred in 77% of participants, resulting in a Black Box Warning in the prescrbing information and the development of a Risk Evaluation and Mitigation Strategy (REMS) program to ensure appropriate and safe use.
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.