General Information

Abecma (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy.

Abecma is specifically indicated 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 monoclonal antibody.

Abecma is supplied as a suspension for intravenous administration. Abecma is provided as a single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive T cells in one or more infusion bags. Each dose of Abecma is a customized treatment created by using a patient's own T-cells, which are a type of white blood cell, to help fight the myeloma. The patient's T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing myeloma cells. Once the cells are modified, they are infused back into the patient. The recommended dose range is 300 to 460 x 106 CAR-positive T cells. 

Clinical Trials

The FDA approval of Abecma was based on KarMMa, a pivotal, open-label, single arm, multicenter, Phase 2 study. KarMMa enrolled 140 patients, of whom 128 patients were treated with idecabtagene vicleucel (ide-cel) across the target dose levels of 150-450 x 106 CAR+ T cells. All treated patients were exposed to at least three prior therapies, including an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an anti-CD38 antibody, and all were refractory to their last regimen. Ninety-four percent of patients were refractory to an anti-CD38 antibody and 84% percent were triple refractory (refractory to an IMiD agent, PI and anti-CD38 antibody). The primary endpoint was overall response rate [ORR]) and key secondary endpoints were complete response rate [CR]), as well as duration of response (DoR) and progression-free survival (PFS) across the target dose levels. The overall response rate was 94%; the CR was 40%, the DoR was 10.6 months and the PFS was 8.6 months. 

Side Effects

Adverse effects associated with the use of Abecma may include, but are not limited to, the following:

• cytokine release syndrome
• infections – pathogen unspecified
• fatigue
• musculoskeletal pain
• hypogammaglobulinemia
• diarrhea
• upper respiratory tract infection
• nausea
• viral infections
• encephalopathy
• edema
• pyrexia
• cough
• headache
• decreased appetite
• laboratory adverse reactions: neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia

The Abecma drug label comes with the following Black Box Warning: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS AND PROLONGED CYTOPENIA

• Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with Abecma. Do not administer Abecma to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with Abecma, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with Abecma. Provide supportive care and/or corticosteroids as needed.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with Abecma. HLH/MAS can occur with CRS or neurologic toxicities.
• Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with Abecma.
• Abecma is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Abecma REMS

Mechanism of Action

Abecma (idecabtagene vicleucel) is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of ABECMA results in CAR-positive T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Additional Information

For additional information regarding Abecma or patients with relapsed or refractory multiple myeloma, please visit the Abecma website.