Long-term follow-up from the CARTITUDE-1 trial demonstrates the curative potential of ciltacabtagene autoleucel (cilta-cel) in patients with relapsed/refractory multiple myeloma (RRMM), with one-third of patients remaining treatment- and progression-free for at least five years after a single infusion.
In the CARTITUDE-1 study, cilta-cel was evaluated in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). These patients have historically poor outcomes, characterised by a median progression-free survival (PFS) of less than six months and a median overall survival (OS) of approximately one year.1 Previously, with a median follow-up of 33.4 months, the study demonstrated a median PFS of 34.9 months. The median OS had not yet been reached, and the 36 month OS rate was 62.9%.2 The five-year follow-up results of the CARTITUDE-1 study were recently published in Journal of Clinical Oncology,3 and presented at EHA 2025.4
Study design
CARTITUDE-1 (NCT03548207) is a phase Ib/II, open-label, multicentre study evaluating cilta-cel in patients (>18 years old) with RRMM who had received at least three prior lines of therapy and were triple-class exposed. A single cilta-cel infusion (target dose 0.75×106 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion. The primary endpoints were safety, confirmation of the recommended phase II dose (phase Ib), and overall response rate (ORR)(phase II) in all patients who received treatment. Key secondary endpoints were duration of response (DoR) and PFS. Following CARTITUDE-1, patients could enrol in CARTinue (NCT05201781), a 15-year post-infusion follow-up study with evaluations based on local standard of care.
Results
Out of 97 patients treated with cilta-cel, 32 patients (33%) remained alive and progression-free for at least five years without additional myeloma treatment. Of these patients, median age was 60 years and the median number of prior treatment lines was 6.5. High-risk cytogenetics were observed in 23.3% of patients, 12.5% had extramedullary disease, 90.6% were triple-class refractory, and 46.9% were penta-drug refractory. Baseline characteristics were similar in patients who experienced progression within five years. Of the patients who were progression-free, 12 patients in stringent complete remission from a single centre underwent serial minimal residual disease (MRD) and PET/CT assessments. All patients (12/12) were MRD-negative (10-6) and imaging-negative at five years or later following treatment infusion. Median OS was 60.7 months.
Biomarkers linked to long-term disease control included a higher proportion of naïve T-cells in the infusion product, lower neutrophil-to-T-cell ratio, higher baseline haemoglobin and platelet counts, and a higher effector-to-target ratio. In patients who remained progression-free for ≥5 years, two developed a secondary malignancy (both solid tumours). Two patients experienced a neurologic event (transient hepatic encephalopathy and taste disorder), and four new grade 3 infections were reported. Neither the neurologic events nor the infections were considered related to treatment with cilta-cel. No new cases of parkinsonism or cranial nerve palsy were reported.
Conclusion
In the CARTITUDE-1 study, one-third of patients remained progression free for at least five years after a single infusion of cilta-cel. The safety profile of cilta-cel remained consistent with previous reports. These findings offer the first evidence that cilta-cel may be potentially curative in RRMM.
References
1. Mateos MV, Weisel K, De Stefano V, et al. LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis). Leukemia. 2024;38(12):2554-60.
2. Lin Y, Martin TG, Usmani SZ, et al. CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Presented at ASCO 2023; Abstract 8009.
3. Jagannath S, Martin TG, Lin Y, 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. 2025.
4. Jagannath S, Martin T, Lin Y, et al. Long-term (>5 year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. Presented at EHA 2025; Abstract S192.
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