CAR-T therapy – Equecabtagene Autoleucel (Fucaso) demonstrates efficacy and safety in heavily pretreated multiple myeloma patients

Fucaso (Equecabtagene autoleucel), a BCMA-directed chimeric antigen receptor (CAR) T cell therapy, has shown deep, durable responses with a favorable safety profile in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM).

These results, published in JAMA Oncology, are based on the single-arm, open-label, phase 1b/2 FUMANBA-1 trial.

Multiple myeloma (MM) is a complex and incurable blood cancer marked by cycles of remission and relapse. According to the Leukemia & Lymphoma Society, nearly all patients with MM will eventually experience relapse or become refractory to treatment, highlighting the urgent need for novel therapeutic strategies. CAR T-cell therapies have garnered significant clinical interest, resulting in numerous clinical trials and subsequent FDA approvals. Real-world data further validate these trial outcomes, reinforcing the potential of CAR T-cell therapy for patients with limited treatment options.

Eque-cel, a BCMA-targeting CAR T-cell therapy, was approved by China’s National Medical Products Administration in June 2023 for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). In April 2024, the FDA accepted the manufacturer’s investigational new drug (IND) application for its use in treating non-renal systemic lupus erythematosus and lupus nephritis, paving the way for clinical trials to begin in the United States.

Of the patients who underwent apheresis, 105 proceeded to lymphodepleting chemotherapy, and 103 received an Eque-cel infusion. Approximately 80% of the patients had stage 2 or 3 disease, with 38.6% presenting high-risk cytogenetics. All patients had previously undergone four lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, while 11.7% had prior CAR T-cell therapy.

At a median follow-up of 13.8 months (range, 0.4-27.2), the overall response rate was 96%, with 74.3% of patients achieving a complete response or better. The median progression-free survival was not reached, but the 12-month progression-free survival rate was 78.8% (95% CI, 68.6–86.0). Minimal residual disease (MRD) negativity, with a sensitivity threshold of 10⁻⁵, was achieved by 95.0% of patients.

Adverse events (AEs) were generally manageable. The most common were grade 1 or 2 cytokine release syndrome (CRS), observed in 92.3% of patients, and grade 1 or 2 immune effector cell-associated neurotoxicity syndrome (ICANS) in 1.9%. Notably, all cases of CRS and ICANS resolved with appropriate treatment.

These findings highlight the potential of equecabtagene autoleucel as a groundbreaking therapy for patients with relapsed or refractory multiple myeloma, particularly those who have exhausted conventional treatment options. The high overall response rate, prolonged progression-free survival, and manageable safety profile emphasize its promise in addressing the significant unmet needs of this patient population. As CAR T-cell therapies advance, Eque-cel marks a pivotal development in improving outcomes for patients with RRMM, especially those with high-risk disease.

REFERENCES

1. Li C, Zhou K, Hu Y, et al. Equecabtagene autoleucel in patients with relapsed or refractory multiple myeloma: The FUMANBA-1 nonrandomized clinical trial. JAMA Oncol. November 7, 2024. doi:10.1001/jamaoncol.2024.4879
2. Phase I/II clinical study of fully human BCMA chimeric antigen receptor autologous T cell injection (CT103A) for the treatment of patients with relapsed/refractory multiple myeloma (FUMANBA-1). Updated August 7, 2021. Accessed January 2, 2025. https://www.chictr.org.cn/showproj.html?proj=53503
3. Refractory and relapsed. Leukemia & Lymphoma Society. Accessed January 2, 2025. https://www.lls.org/myeloma/treatment/refractory-and-relapsed
4. Equecabtagene autoleucel injection approved with conditions by China NMPA. National Medical Products Administration. June 30, 2023. Accessed January 2, 2025. https://english.nmpa.gov.cn/2023-06/30/c_940315.htm
5. FDA approves IASO Bio’s IND for equecabtagene autoleucel. Pharmaceutical Technology. August 12, 2024. Accessed January 2, 2025. https://www.pharmaceutical-technology.com/news/fda-iaso-bios-ind/
6. Eque-cel elicits responses in heavily pretreated multiple myeloma. Cancer Therapy Advisor. November 14, 2024. Accessed January 2, 2025. https://www.cancertherapyadvisor.com/news/eque-cel-elicits-responses-in-heavily-pretreated-multiple-myeloma/#xd_co_f=YWRmMGFmM2YtMmFiZS00YjA3LTlhOWUtMDljYWFlMDYwYmVj~