Single Cilta-cel Infusion Leaves Half of Patients With Early-Line Myeloma Progression-Free at 5 Years

AJMC® Staff

Half of patients with relapsed/refractory multiple myeloma (RRMM) who received a single infusion of ciltacabtagene autoleucel, or cilta-cel (Carvykti; Legend/Johnson & Johnson) after 1 to 3 prior lines of therapy were still alive and progression-free at least 5 years later without maintenance therapy. The finding comes from long-term results of the phase 2 CARTITUDE-2 study (NCT04133636).¹

The results were from the initial subgroup of cohort A and were presented September 25, 2026, at the International Myeloma Society (IMS) Annual Meeting in Glasgow, Scotland.¹ They build on CARTITUDE-1 (NCT03548207), in which 33% of heavily pretreated patients (32 of 97) were alive and progression-free at least 5 years after a single cilta-cel infusion.² Taken together, the 2 studies suggest that giving the B-cell maturation antigen (BCMA)–directed CAR T-cell therapy earlier may raise the share of patients who reach long-term remission without further treatment.

Cilta-cel was developed by Johnson & Johnson and Legend Biotech. In April 2024, the FDA approved it for adults with RRMM who are refractory to lenalidomide and have had at least 1 prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent.³

Cohort A enrolled 20 patients with RRMM. All had received 1 to 3 prior lines of therapy, had been exposed to a PI and an immunomodulatory drug, and were refractory to lenalidomide. The primary end point was minimal residual disease (MRD) negativity. Patients had a median of 2 prior lines. Of the 20, 85% had undergone autologous stem cell transplant, 65% were triple-class exposed, and 40% were triple-class refractory.⁴

Five-year results

At a median follow-up of 60.7 months (range, 3.3-63.1), 95% of patients (n = 19) had a complete response or stringent complete response as their best response.¹

Ten patients (50%) were still alive and progression-free, with no further antimyeloma treatment, at least 5 years after infusion. Median progression-free survival (PFS) was 60.5 months (95% CI, 12.9-not estimable), and the 60-month PFS rate was 54.2% (95% CI, 30.3%-73.0%). Median overall survival (OS) was not reached, and the 60-month OS rate was 69.2% (95% CI, 43.8%-84.9%).¹

The protocol did not require a bone marrow assessment at 5 years. All 3 patients who had one were MRD negative at the 10^-6 threshold.¹

Among the 10 patients who were progression-free long term, 7 had cytogenetic data available. Of those 7, 5 had at least 1 high-risk abnormality and 4 had 2 or more.²

Patients who were progression-free at 5 years tended to start treatment with less disease. Their median bone marrow plasma cell level was 20%, compared with 40% among patients who progressed. They also had higher levels of CD4+ naive T cells at apheresis (P = .036) and of CAR-positive CD4+ central memory T cells at peak expansion (P = .019).¹

“Five years ago, treatment-free remissions of this duration were difficult to imagine for many patients with relapsed or refractory multiple myeloma,” Niels van de Donk, MD, PhD, professor of hematology at Amsterdam University Medical Center, the Netherlands, said in a statement. “These new CARVYKTI findings provide additional evidence that when highly effective, established therapies are used earlier in the disease course, more patients may have the opportunity to achieve deep, durable remissions and long-term disease control without maintenance.”⁵

Safety

With longer follow-up, the safety profile was consistent with earlier reports. No new CAR T-cell–related neurotoxicity was reported, including cranial nerve palsy or parkinsonism.¹

Since the 30-month analysis, 5 patients (25%) have developed second primary malignancies, which were judged unrelated to cilta-cel. The cancers were acute myeloid leukemia, breast cancer, prostate cancer, basal cell carcinoma, melanoma in situ, and squamous cell carcinoma; 1 patient had 2 of them. There were 2 new deaths. One was from progressive disease. The other was from breast cancer in a patient who had been progression-free at 5 years.¹

The analysis is limited by its small sample and single-arm design.

References

1. Cohen AD, Mateos MV, Cohen YC, et al. Long-term (≥5-year) remission and survival with ciltacabtagene autoleucel (cilta-cel) in relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy: CARTITUDE-2 cohort A. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Poster PA-288.
2. 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;43(25):2766-2771. doi:10.1200/JCO-25-00760
3. Carvykti. Prescribing information. Janssen Biotech, Inc; 2025. Accessed October 29, 2026. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf
4. Hillengass J, Cohen AD, Agha M, et al. The phase 2 CARTITUDE-2 trial: updated efficacy and safety of ciltacabtagene autoleucel in patients with multiple myeloma and 1-3 prior lines of therapy (cohort A) and with early relapse after first line treatment (cohort B). Presented at: 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA.
5. Single infusion of CARVYKTI^® (ciltacabtagene autoleucel) delivered five-year treatment-free remissions in 50% of patients in early line relapsed/refractory multiple myeloma. News release. Johnson & Johnson. September 25, 2026. Accessed October 29, 2026. https://www.jnj.com/media-center/press-releases/single-infusion-of-carvykti-ciltacabtagene-autoleucel-delivered-five-year-treatment-free-remissions-in-50-of-patients-in-early-line-relapsed-refractory-multiple-myeloma