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.