A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti) improved long-term survival among patients with heavily pretreated relapsed/refractory multiple myeloma without any maintenance treatment, according to a post-hoc analysis of the CARTITUDE-1 trial.
Among 97 patients, 45 were still alive and in long-term follow-up, with a median overall survival (OS) of 60.7 months, reported Peter Voorhees, MD, of the Wake Forest University School of Medicine in Charlotte, North Carolina, during a session at the American Society of Clinical Oncology (ASCO) annual meeting.
Moreover, 32 patients were alive and progression-free without any further anti-myeloma treatment 5 or more years after treatment with cilta-cel.
Of these progression-free patients, 12 from a single center with serial minimal residual disease (MRD) assessments were all MRD-negative and imaging-negative at year 5 or later after cilta-cel without additional therapy, "suggesting a potential cure, or at bare minimum, unprecedented durability of complete response," Voorhees said.
Results from this updated analysis were also published in the Journal of Clinical Oncology.
The results "are remarkable, given the historically dismal prognosis for this population with a [median OS] of approximately 1 year," Voorhees and co-authors wrote. "No therapies currently approved for the treatment of triple-class exposed/refractory [multiple myeloma] achieve similar outcomes; moreover, existing regimens typically require ongoing therapy and are often associated with relapse."
ASCO discussant Krina Patel, MD, MSc, of the University of Texas MD Anderson Cancer Center in Houston, noted that "ciltacabtagene autoleucel is the first potential functional cure for patients with modern-day relapsed/refractory multiple myeloma."
Patel said the study's progression-free survival (PFS) curve -- which seemed to have completely flattened out at about 60 months -- "is worth another look."
"This might be the first time we have a plateau," she explained. "I do hope this plateau continues forever for these 33% of patients where we can say it's a true cure. I won't hold my breath, because most of my patients do relapse at some point. But I was really excited about this curve when I saw it."
CARTITUDE-1 was a phase Ib/II, open-label, multicenter study of cilta-cel in patients with relapsed/refractory multiple myeloma. Enrolled patients had undergone three or more previous lines of therapy and were triple-class exposed.
Among 97 patients infused (median age 61, 58.5% men), 97% were refractory to daratumumab (Darzalex), 25.3% had high-risk cytogenetics, 13.4% had extramedullary plasmacytomas, and 87.6% were triple-class refractory. The median time from start of last line of therapy to progression was 4.2 months.
In the original study, median PFS was 34.9 months, and median OS was not reached.
Based on these results, cilta-cel was initially approved by the FDA for patients with relapsed/refractory multiple myeloma after four or more previous lines of therapy. Approval was subsequently expanded to relapsed, lenalidomide (Revlimid)-refractory multiple myeloma with one or more previous lines of therapy based on results from CARTITUDE-4.
Voorhees and colleagues reported that the baseline characteristics were similar between patients who were progression-free at 5 or more years and those who progressed. The median number of previous lines of therapy was 6.5 versus 5, 23.3% versus 26.7% had high-risk cytogenetics, and 12.5% versus 13% had extramedullary plasmacytomas.
"Importantly, long-term remission was not limited to standard-risk disease," Voorhees observed.
However, "there was a difference in the burden of disease between these two groups of patients," he added.
Specifically, the percentage of patients with high tumor burden was lower (6.3% vs 17.4%) among progression-free patients, who also had numerically lower median soluble B-cell maturation antigen levels (36.0 μg/L vs 58.5 μg/L) and median bone marrow plasma cells (5% vs 24%).
"This would suggest that a lower burden of disease going into cilta-cel infusions does predict for better long-term outcomes," Voorhees said.
He also reported that patients in long-term remission had more fit immune T-cell phenotypes, and a higher effector-to-target ratio at peak CAR T-cell expansion. "The bottom line is that it appeared there is a signal for more immune-fit CAR T-cell products leading to durable remissions," he said.
With the longer follow-up in progression-free patients, Voorhees reported that there were no new cases of parkinsonism or other cases of delayed neurotoxicities. There were two second primary malignancies (both solid tumors), two neurologic adverse events, and four grade ≥3 infections (not related to cilta-cel).
Disclosures
The study was supported by Johnson & Johnson and Legend Biotech.
Voorhees reported consulting or advisory roles with AbbVie/Genentech, Bristol Myers Squibb, Pfizer, Sanofi, Janssen, GSK, Regeneron, Ascentage Pharma, AstraZeneca, and Kite, and research funding from AbbVie, Janssen, GSK, TeneoBio, and Regeneron.
Patel reported relationships with Bristol Myers Squibb/Celgene, Kite, Oricell Therapeutics, AbbVie, AstraZeneca, Janssen, Legend Biotech, Merck, Novartis, Pfizer, Regeneron, Takeda, Indapta Therapeutics, and Nektar.
Primary Source
Journal of Clinical Oncology
Source Reference: Jagannath S, 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; DOI: 10.1200/JCO-25-00760.
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