FDA Accepts sBLA for Cilta-Cel in Lenalidomide-Refractory Multiple Myeloma

“Cilta-cel has the potential to be a new standard of care for patients with lenalidomide-refractory myeloma after first relapse,” lead study author Binod Dhakal, MD, an associate professor at the Medical College of Wisconsin in Milwaukee, said in a presentation of data from the CARTITUDE-4 study.

The FDA has accepted a supplemental biologics license application (sBLA) for ciltacabtagene autoleucel (cilta-cel; Carvykti) for the management of relapsed or refractory multiple myeloma previously treated with at least 1 line of therapy including a proteasome inhibitor, an immunomodulatory agent, and lenalidomide (Revlimid), according to a press release from the Janssen Pharmaceutical Companies of Johnson & Johnson.¹

“We look forward to collaborating with the FDA on the review of this application and continuing to bring [cilta-cel] to patients who are candidates for this CAR T therapy,” Peter Lebowitz, MD, PhD, Global Therapeutic Area head at Janssen Research and Development, LLC, said in the press release.

Supporting data for the sBLA came from the phase 3 CARTITUDE-4 study (NCT04181827), in which investigators assessed the safety and efficacy of cilta-cel vs standard-of-care therapy with pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd) among patients with lenalidomide-refractory multiple myeloma.

According to findings presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine, treatment with cilta-cel produced a median progression-free survival (PFS) that was not reached (NR; 95% CI, 22.8 months-not estimable [NE]) vs 11.8 months (95% CI, 9.7-13.8) with standard of care.^2,3 Additionally, the 12-month PFS rates in the cilta-cel and standard of care arms, respectively, were 76% vs 49%.

Investigators reported PFS benefit with cilta-cel across all prespecified subgroups, including those who received 1 prior line of therapy (Hazard ratio [HR], 0.35; 95% CI, 0.19-0.66) or 2 or 3 prior lines of therapy (HR, 0.24; 95% CI, 0.16-0.37).

“Cilta-cel has the potential to be a new standard of care for patients with lenalidomide-refractory myeloma after first relapse,” lead study author Binod Dhakal, MD, an associate professor at the Medical College of Wisconsin in Milwaukee, said in a presentation of data from the CARTITUDE-4 study.

In the CARTITUDE-4 trial, patients were randomly assigned 1:1 to receive cilta-cel or standard of care with physician’s choice of PVd or DPd. At 5 to 7 days following lymphodepletion with 300 mg/m² of cyclophosphamide and 30 mg/m² of fludarabine per day for 3 days, patients received cilta-cel at a target dose of 0.75 x 10⁶ CAR T cells/kg.

The primary end point of the trial was PFS. Secondary end points included complete response rate or better, overall response rate, minimal residual disease negativity, overall survival, and safety.

Patients 18 years and older who received 1 to 3 prior lines of therapy for multiple myeloma and were refractory to lenalidomide were eligible for enrollment on the trial. Additionally, patients needed to have an ECOG performance status of 0 or 1 to enroll.

Grade 3/4 adverse effects (AEs) occurred in 96.6% of patients receiving cilta-cel vs 94.2% of those receiving standard of care. Additionally, any-grade serious AEs (SAEs) occurred in 44.2% vs 38.9% of patients in each respective treatment group, and grade 3/4 SAEs occurred in 32.2% vs 33.7% of patients.

The most common any-grade hematologic treatment-emergent AEs (TEAEs) in the cilta-cel and standard of care arms, respectively, included neutropenia (89.9% vs 85.1%), anemia (54.3% vs 26.0%), thrombocytopenia (54.3% vs 31.3%), and lymphopenia (22.1% vs 13.9%). Grade 3/4 TEAEs included neutropenia (89.9% vs 82.2%), thrombocytopenia (41.3% vs 18.8%), and anemia (35.6% vs 14.4%).

The FDA previously approved cilta-cel for patients with relapsed/refractory multiple myeloma following 4 or more lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody in February 2022.⁴ The approval was based on data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207).

References

1. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of CARVYKTI® for the earlier treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. June 6, 2023. Accessed June 7, 2023. bit.ly/3qA1Aig
2. Dhakal B, Yong K, Harrison SJ, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. J Clin Oncol. 2023;41(suppl 17):LBA106. doi:10.1200/JCO.2023.41.17_suppl.LBA106
3. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. Published online June 5, 2023. doi:10.1056/NEJMoa2303379
4. U.S. FDA Approves CARVYKTI (ciltacabtagene autoleucel), Janssen's first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed June 7, 2023. https://prn.to/3vskiZu