Bluebird CAR-T Multiple Myeloma
Bluebird CAR-T Multiple Myeloma
Abecma is the world’s first approved BCMA-targeted CAR-T cell therapy, co-developed by Bristol Myers Squibb (BMS) and Bluebird Bio. It is a first-in-class, BCMA-directed, personalized immune cell therapy administered as a one-time intravenous infusion for the treatment of patients with relapsed or refractory multiple myeloma (MM) after three or more prior lines of therapy.
The recommended dose of Abecma is 300-460 x 10E6 CAR-positive T cells. BCMA (B-cell maturation antigen) is a protein widely expressed on multiple myeloma cancer cells. As an anti-BCMA CAR-T cell therapy, Abecma recognizes and binds to BCMA, leading to the death of BCMA-expressing cells.
Abecma was initially approved in the European Union in May 2020 and subsequently in the United States in March 2021 for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. On April 4, 2024, the FDA further expanded the approval of Abecma (idecabtagene vicleucel, ide-cel) for the treatment of multiple myeloma patients who have received at least two prior therapies.
Notably, Abecma is the world’s first BCMA-directed CAR-T cell therapy to receive regulatory approval and the fifth CAR-T cell therapy approved by the U.S. FDA.
The mechanism of action of Abecma involves engineering a patient’s T cells to express a BCMA-targeted chimeric antigen receptor (CAR). The manufacturing process involves isolating T cells from the patient’s blood, modifying them using a lentiviral vector encoding the BCMA CAR, and expanding the engineered CAR-T cells. Prior to Abecma infusion, patients undergo lymphodepleting chemotherapy (cyclophosphamide and fludarabine) to eliminate existing T cells, followed by the infusion of ide-cel. Once infused, ide-cel seeks out and kills BCMA-expressing cells.
Abecma is part of a co-development, co-promotion, and profit-sharing agreement between BMS and Bluebird Bio. Their comprehensive Abecma clinical development program includes several studies (KarMMa-2, KarMMa-3, KarMMa-4) investigating its use in earlier lines of MM treatment, including newly diagnosed patients.
Beyond Abecma, BMS and Bluebird Bio are also developing bb2127, a next-generation anti-BCMA CAR-T therapy. Building upon the first-generation Abecma, bb2127 incorporates a PI3K inhibitory signaling domain to enrich for longer-lived, more potent “memory” T cell subsets with improved anti-tumor activity.