Seven chimeric antigen receptor (CAR) T-cell therapies to help patients’ immune systems fight cancer were approved by the FDA in 2024. They include the novel therapy obecabtagene autoleucel, or obe-cel (Aucatzyl, Autolus), and six approvals for expanded indications for three other products.
The growth in available CAR T-cell therapies makes it “definitely an exciting time,” said Mary McGann, PharmD, BCOP, a clinical pharmacy specialist in bone marrow transplant and cellular therapy at the Medical University of South Carolina, in Charleston. “I feel like every year we almost double the number of CAR-T patients that we have.”
Obe-cel, an autologous T-cell therapy that is genetically modified to target cells that express the biomarker CD19, was approved Nov. 8, 2024, for the treatment of adults with relapsed or refractory B-cell precursor or acute lymphoblastic leukemia (B-ALL).
“Patients with B-cell ALL that is refractory to induction therapy or after multiple relapses have very few meaningful treatment options, and represent a population with an unmet medical need that warrants novel [management] strategies,” said Najat Bouchkouj, MD, the associate director of pediatrics in the Office of Clinical Evaluation, Office of Therapeutic Products at the FDA, during a presentation at the 2024 American Society of Hematology Annual Meeting & Exposition, in San Diego.
Approval was based on results of the multicenter, multiphase FELIX study (N Engl J Med 2024;391[23]:2219-2230) that evaluated obe-cel in adults with relapsed or refractory B-cell ALL. The primary end point was overall remission at any time after product infusion. Secondary end points included duration of remission and complete remission within three months after product infusion. Phase 2 of the study was designed to include a sample size of 49 patients. Study participants received obe-cel as a split dose of 410 million cells administered on days 1 and 10. Among 112 patients who underwent leukapheresis before receiving obe-cel, 65 comprised the primary efficacy analysis set. The median age was 51 years and 54% were female.
The rate of complete remission was 42% within three months of infusion and the median duration of response was 14.1 months, Dr. Bouchkouj said. Overall complete remission at any time following treatment was observed in 63% of participants, with a duration of 14.1 months.
A safety analysis was conducted on 100 patients enrolled in the phase I and phase 2 cohorts who received at least one infusion of obe-cel. The prescribing information has boxed warnings for cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS) and T-cell malignancies, she said. Other warnings include prolonged cytopenias, infections and secondary malignancies.
Fatal adverse reactions were seen in 9% of patients due to infections, ICANS and other issues; serious adverse reactions such as febrile neutropenia and CRS were seen in 62%. Grade 3 or higher reactions occurred in at least 20% of participants, said Dr. Bouchkouj, but the incidence of all-grade CRS and neurotoxicity were comparable to other approved CAR T-cell therapies.
Due to concerns about the product’s long-term safety, the FDA has required a postmarketing observational study to collect additional safety information, disease and survival outcomes for 15 years, she said. Additionally, obe-cel was approved with a requirement to conduct a molecularly targeted pediatric cancer investigation in the postmarketing setting to evaluate dosing, pharmacokinetics, safety and anti-tumor activity in pediatric patients age 1 year and older who have B-cell malignancies.
“This approval does not establish how the product should be placed in the treatment armamentarium of adults with ALL,” Dr. Bouchkouj said. “Further studies are needed to improve the outcomes and establish the optimal sequencing of therapies based on safety and efficacy considerations.”
There are several features of obe-cel that pharmacists should note, Dr. McGann said. One is the split dosing. Another is that patients need to have a bone marrow biopsy within seven days of starting to determine the appropriate dose, with patients with a higher disease burden instructed to receive a lower dose to limit the toxicity burden. “It’ll definitely take pharmacist involvement in determining or confirming that we’re giving patients the right dose, and guiding the team through that,” she told Pharmacy Practice News.
Other products approved for expanded indications last year include:
Lisocabtagene maraleucel/liso-cel (Breyanzi, Bristol Myers Squibb). Liso-cel received new approvals for chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two lines of therapy. In 2024, liso-cel also was approved for follicular lymphoma after at least two lines of therapy, and for mantle cell lymphoma after at least two lines of therapy. It originally was approved in 2021 for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.
Idecabtagene vicleucel/ide-cel (Abecma, Bristol Myers Squibb). Ide-cel, approved in 2021 for the treatment of relapsed or refractory multiple myeloma after four or more lines of therapy, in 2024 received an expanded indication for triple-class–exposed relapsed or refractory multiple myeloma after two or more prior lines of therapy.
Ciltacabtagene autoleucel/cilta-cel (Carvykti, Johnson & Johnson). Cilta-cel in 2024 received an expanded indication for relapsed or refractory multiple myeloma following one line of therapy. It was first approved in 2022 for multiple myeloma after four or more prior lines of therapy.
The prescribing information for cilta-cel contains a boxed warning that the drug sometimes causes ICANS, which may be fatal or life-threatening. According to Dr. McGann, ICANS can be accompanied by Parkinson-like features (also mentioned in the boxed warning) or cranial nerve palsies (cited in the main section) that may emerge a month or more after treatment. “This is important for pharmacists to know, because patients [receiving therapy] are at their academic medical center for the first month and then go home and have follow-up appointments locally.”
Late cytopenia and infections are additional reactions to note, she said.
“Everyone thinks of the first two weeks to a month [after CAR T-cell therapy] being really intense, but we’re starting to learn more that there is definitely substantial toxicity beyond that that needs close follow-up and supportive care and monitoring,” Dr. McGann said.
Dr. Bouchkouj reported no relevant financial disclosures. Dr. McGann served on a one-time advisory board for Sanofi.
This article is from the March 2025 print issue.