Single Infusion of Cilta-Cel Yields 5-Year Progression-Free Survival in Multiple Myeloma

A single dose of ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech, Inc) yielded long-term remission without maintenance therapy in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). The data from the CARTITUDE-1 trial (NCT03548207) suggest the curative potential of cilta-cel for those with advanced disease.¹

Visualization of CAR T-cells | Image Credit: © furyon - stock.adobe.com

MM is an incurable blood cancer characterized by the overproduction of lymphocytes in the bone marrow. The heterogeneity of the disease makes it particularly challenging to treat, and the pathway to a cure remains uncertain. Over the past 2 decades, treatment of MM has significantly improved, and many patients can live up to 10 years; however, one of the core challenges in treating MM is that responses to therapy tend to diminish with each subsequent line of treatment, especially those with advanced disease. Cilta-cel, a chimeric antigen receptor (CAR) T-cell therapy, may offer patients a treatment approach with lasting remission and curative potential.²

Cilta-cel is a BCMA-directed CAR T-cell therapy that targets overexpressed BCMA proteins on the surface of malignant myeloma cells. According to prior investigations, approximately 90% of patients with MM exhibit an overexpression of BCMA, which led to it becoming a significant therapeutic target for patients. Cilta-cel was originally approved by the FDA in 2022 for the treatment of adult patients with RRMM who have previously received 4 or more lines of therapy. In 2024, it received an additional indication for patients with RRMM who had at least 1 line of prior therapy.²

The FDA approval for cilta-cel was based on data from the CARTITUDE-1 trial, a phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in patients with RRMM who underwent 3 or more prior lines of therapy and were triple-class exposed. The data showed that about 98% of patients receiving the CAR T-cell product achieved an overall response rate with a duration of response of 21.8 months.²

In a post-hoc analysis, investigators report that one-third of patients from the trial remain alive and progression-free for 5 or more years without maintenance therapy. Of these, 12 patients treated at one center had regular tests to check for minimal residual disease (MRD) and imaging scans, and all 12 showed no signs of disease (MRD-negative at a threshold of at least 10^-5 and imaging-negative) at year 5 or later.³

Baseline features—such as high-risk genetic markers or disease outside the bone marrow—were generally similar between the long-term responders and those whose disease came back within 5 years. However, patients who stayed progression-free for 5 years tended to have lower tumor burden at baseline, more naïve T-cells in the cilta-cel product, a higher T-cell-to-neutrophil ratio, higher hemoglobin and platelet counts, and a higher effector-to-target ratio.³

“To our knowledge,” the authors concluded, “we show the first evidence of the curative potential of cilta-cel with a third of patients remaining treatment-free and progression-free for at least 5 years after a single infusion.”³

REFERENCES

1. 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). Updated April 2, 2024. Accessed June 9, 2025. https://www.clinicaltrials.gov/study/NCT03548207

2. Gerlach A. Real-world outcomes show efficacy, safety of ciltacabtagene autoleucel in relapsed, refractory multiple myeloma. Pharmacy Times. January 6, 2025. Accessed June 9, 2025. https://www.pharmacytimes.com/view/real-world-outcomes-show-efficacy-safety-of-ciltacabtagene-autoleucel-in-relapsed-refractory-multiple-myeloma

3. Jagannath S, Martin T, Cohen A, et al. Long-term (≥5-year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol. June 3, 2025. Accessed June 9, 2025. doi: 10.1200/JCO-25-00760