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FDA Approves Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma

Multiple myeloma cells.

The FDA has approved ciltacabtagene autoleucel (CarvyktiTM, Janssen Biotech) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least four prior lines of treatment, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

"Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR) T-cell therapy with 2 B-cell maturation antigen (BCMA)–targeting single-domain antibodies, demonstrated early, deep, and durable responses in the phase 1b/2 CARTITUDE-1 study in patients with relapsed/refractory multiple myeloma who have been heavily pretreated," wrote Thomas G. Martin, MD, Clinical Professor of Medicine at the Helen Diller Family Comprehensive Cancer Center of the University of California, San Francisco, and colleagues, in their publication of the CARTITUDE-1 study (NCT03548207), on which the approval was based. Dr. Martin presented updated results of the trial at the 63rd American Society of Hematology Annual Meeting & Exposition in December.

The CARTITUDE-1 trial enrolled 97 patients with multiple myeloma who had received at least three prior therapies. Bridging therapy was permitted after apheresis. Following lymphodepletion consisting of 300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for three days, patients received a single infusion of cilta-cel, with a target dose of 0.75x106 CAR-positive viable T cells/kg, for five to seven days. The primary end points were efficacy, safety, and confirmation of the recommended phase 2 dose.

At a median follow-up of 18 months, cilta-cel produced an overall response rate of 98%, with 94.8% of patients experiencing a very good partial response or better and 80.4% of patients experiencing a stringent complete response. The median duration of response was 21.8 months. Among 61 patients who were evaluated for minimal residual disease (MRD) negativity, 91.8% were MRD-negative at the threshold of 10-5, which was sustained for at least 6 months in 44.3% of patients and for at least 12 months in 18.0% of patients.

Grade 3/4 hematologic adverse events experienced by ≥25% of patients included neutropenia (94.8%), anemia (68.0%), leukopenia (60.8%), thrombocytopenia (59.8%), and lymphopenia (49.5%). Cytokine release syndrome (CRS) occurred in 94.8% of patients and was primarily grade 1 or 2. The median time to onset of CRS was 7 days, and it resolved within 14 days in 98.9% of patients. There were no new incidences of CAR T-cell–related neurotoxicity since previously reported results of the study.

Cilta-cel is only available through Risk Evaluation Mitigation Strategy (REMS)–certified health care facilities. The prescribing information includes a boxed warning that cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), Parkinsonism and Guillain-Barré syndrome, and prolonged or recurrent cytopenias may occur.

"At a longer median follow-up of 18 months, a single cilta-cel infusion led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma," concluded Dr. Martin and colleagues in their presentation abstract. "Cilta-cel demonstrated a manageable safety profile with no new safety signals observed with longer follow-up."

The recommended dose range of cilta-cel, following a lymphodepleting regimen of cyclophosphamide and fludarabine, is 0.5-1.0x106 CAR-positive viable T cells per kg of body weight, with a maximum dose of 1x108 per single-dose infusion.

For More Information

Martin T, Usmani SZ, Berdeja JG, et al (2021). Updated results from CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma [oral presentation]. 63rd American Society of Hematology Annual Meeting & Exposition. Abstract 549.

Clinicaltrials.gov (2022). A study of JNJ-68284528, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). NLM identifier: NCT03548207.

CarvyktiTM (ciltacabtagene autoleucel) prescribing information (2022). Janssen Biotech. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf

Business Wire (2022). CARVYKTITM (ciltacabtagene autoleucel), BCMA-directed CAR-T therapy, receives U.S. FDA approval for the treatment of adult patients with relapsed or refractory multiple myeloma. Available at: https://www.businesswire.com/news/home/20220228006246/en/CARVYKTI%E2%84%A2-ciltacabtagene-autoleucel-BCMA-Directed-CAR-T-Therapy-Receives-U.S.-FDA-Approval-for-the-Treatment-of-Adult-Patients-With-Relapsed-or-Refractory-Multiple-Myeloma

Image credit: KGH. Licensed under CC BY-SA 3.0 


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