Five-Year CARTITUDE-1 Data Highlight Cilta-Cel’s Lasting Impact in RRMM

Historically, the expected median progression-free survival (PFS) among patients with robustly pretreated relapsed or refractory multiple myeloma (RRMM) is 6 months of less, and median overall survival (OS) is approximately 1 year. At a median follow-up of 33.4 months in the CARTITUDE-1 trial (NCT03548207), which was designed to evaluate ciltacabtagene autoleucel (cilta-cel) in patients with RRMM, median PFS was 34.9 months, and median OS was not reached (36-month OS rate, 62.9%; Lin et al, ASCO 2023).

The 15-year follow-up study, CARTinue (NCT05201781), monitors patients for progression, survival, and safety. Patient evaluations per local standard of care are reported annually. During an oral abstract session at the 2025 ASCO Annual Meeting, Peter M. Voorhees, MD, and colleagues reported OS, progression-free outcomes after 5 or more years, and safety outcomes at a median study follow-up of 60.3 months.

Study participants received a single cilta-cel infusion. Drug product baseline and postinfusion samples were used to perform correlative analyses.

Thirty-two of the 97 patients treated (33.0%) remain alive and progression free at 5 or more years after cilta-cel infusion, with no further MM treatment. Before enrollment in CARTITUDE-1, median time from initiation of last line of therapy to progression was 4.0 months for those 32 patients (range, 0.7-48.6 months). Median age was 60 years (range, 43-78 years); median number of prior last lines of therapy was 6.5 (range, 3-14).

Of the 32 patients, 23.3% had high-risk cytogenetics, 12.5% had extramedullary disease (EMD), 90.6% had triple-class refractory disease, and 46.9% had penta-drug refractory disease. The patients in the cohort that remained progression free for 5 or more years, including those with high-risk cytogenetics and EMD, were similar in baseline characteristics to those who had progressive disease (PD) within 5 years.

Results of comparison between patients who had PD within 5 years and those who were progression free for 5 or more years revealed biomarkers significantly associated with progression-free status after 5 or more years, including a greater fraction of naive T cells in the drug product, lower neutrophil to T-cell ratio, higher baseline hemoglobin and platelet values, and higher effector (drug at maximum serum concentration [Cmax]) to target (soluble B-cell maturation antigen) ratio at baseline. The patients in the progression-free cohort also had a significantly greater number of CD4 central memory chimeric antigen receptor–positive (CAR+) T-cell subsets and CAR+ T cells that were positive for the activation markers CD38, CD25, and PD-1 at Cmax.

In a subset of 12 patients at a single center where local serial measurable residual disease (MRD) assessments were performed, all those who were progression free for 5  or more years were MRD negative at 10^–6 and imaging negative by PET/CT yearly for 5 years.

In patients in CARTITUDE-1 with median follow-up of 60.3 months (n=97), median OS was 60.6 months. Three additional patients reported a second primary malignancy during continued follow-up, including one with acute myeloid leukemia onset, 2.8 years after infusion. No new cases of movement and neurocognitive disorders were reported.

In summary, the researchers said, “The median OS for pts [patients] enrolled in CARTITUDE-1 was 5 y [years], and 33% of pts remain progression free for ≥5 y following a single cilta-cel infusion, These data provide the first evidence that cilta-cel is potentially curative in pts with RRMM.”