Cilta-Cel Shows Long-Term Treatment-Free Remissions in Lenalidomide-Refractory Myeloma

A single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti) led to long-term remissions without further antimyeloma therapy in a subset of patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy and were refractory to lenalidomide (Revlimid), according to updated data from cohort A of the phase 2 CARTITUDE-2 trial (NCT04133636) presented in a poster session at the 2026 International Myeloma Society (IMS) Annual Meeting (IMS 2026).¹

At a median follow-up of 60.7 months (range, 3.3-63.1), 50% of patients in cohort A (n = 20) remained alive and progression free at least 5 years after infusion without further antimyeloma treatment. The median progression-free survival (PFS) was 60.5 months (95% CI, 12.9-not evaluable [NE]), and the 5-year PFS rate was 54.2% (95% CI, 30.3%-73.0%). Moreover, the median overall survival (OS) was not reached (95% CI, 21.9-NE), and the 5-year OS rate was 69.2% (95% CI, 43.8%-84.9%).

Among patients who were alive and progression free at 5 years or later, 3 underwent bone marrow assessment at that point, which was not required per protocol, and all 3 were negative for minimal residual disease (MRD) at the 10⁻⁶ threshold.^1,2 Of the remaining 10 patients, 7 had progressive disease or died of progressive disease before 5 years, and 1 withdrew without progression; 2 died of adverse effects (AEs) before 5 years.

Investigators noted numerically higher PFS and OS than in the phase 1b/2 CARTITUDE-1 trial (NCT03548207), which enrolled patients with at least 3 prior lines of therapy.¹ In CARTITUDE-1 (n = 97), the median PFS was 33.3 months (95% CI, 25.2-50.4) and the median OS was 60.7 months (95% CI, 41.9-NE).

Moreover, in CARTITUDE-2, the best response was complete response or stringent complete response (sCR) in 95% of patients; the remaining patient had a minimal response and died of COVID-19 pneumonia.

"Only cilta-cel has demonstrated evidence of durable 5-year treatment-free remissions in [relapsed/refractory multiple myeloma], now with 50% of patients in remission in a CARTITUDE-4–like population," wrote lead study author Adam D. Cohen, MD, and coauthors. Cohen is with the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, in Philadelphia.

How was CARTITUDE-2 cohort A designed?

CARTITUDE-2 is a multicohort study examining cilta-cel across clinical settings in multiple myeloma. Cohort A, the initial subgroup, enrolled patients with progressive disease per International Myeloma Working Group criteria, an Eastern Cooperative Oncology Group performance status no higher than 1, measurable disease, and lenalidomide-refractory disease after 1 to 3 prior lines of therapy that included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). After apheresis and bridging therapy as needed, patients received lymphodepletion with cyclophosphamide at 300 mg/m² and fludarabine at 30 mg/m², both daily for 3 days, followed by cilta-cel at a target dose of 0.75 × 10⁶ CAR-positive viable T cells/kg.

The primary end point of the study was the rate of MRD negativity at the 10⁻⁵ threshold by next-generation sequencing or next-generation flow, assessed by a central laboratory. Secondary end points included overall response rate (ORR), duration of response, time to response (TTR), and safety; PFS and OS served as exploratory end points. After cohort completion, patients were asked to enroll in CARTinue (NCT05201781), a 15-year post-infusion follow-up study; 14 of the 20 eligible patients enrolled.

What came before with cilta-cel?

Initial subgroup analysis data for cohort A of CARTITUDE-2 showed that at a median follow-up of 29.9 months (range, 3.3-35.6), the ORR was 95% in evaluable patients (n = 20), which included a sCR of 85%, a complete response rate of 5%, and a very good partial response rate of 5%.³ The median TTR was 0.99 months (range, 0.7-3.3) and the median time to best response was 3.25 months (range, 0.9-13.6). The 6-, 12-, 15-, and 24-month PFS rates were were 95% (95% CI, 69.5%-99.3%), 84% (95% CI, 59.1%-94.7%), 70% (95% CI, 45.1%-85.3%), and 75% (95% CI, 50.0%-88.7%), respectively. The OS rate at 24 months was 75% (95% CI, 50.0%-88.7%).

The population mirrors that of the phase 3 CARTITUDE-4 trial (NCT04181827), which supported the 2024 FDA approval of cilta-cel for adults with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a PI and an IMiD, and who are refractory to lenalidomide.⁴ Updated CARTITUDE-4 data have also shown an OS benefit with cilta-cel vs standard of care.⁵

In the analysis presented at IMS 2026, what factors distinguished patients with durable remissions?

Compared with patients who had progressive disease or died of progressive disease before 5 years (n = 7), durable responders (n = 10) showed a trend toward lower baseline tumor burden.¹ Bone marrow plasma cells made up 30% or less of the marrow in 90.0% of durable responders vs 42.9% of patients who progressed or died, and 60.0% vs 42.9% of patients, respectively, experienced a decrease in tumor burden between screening and infusion. The median time from the start of the last line of therapy to progression on that line was 12.8 months (range, 1.5-43.2) vs 5.7 months (range, 1.0-41.7).

Durable remissions were not confined to patients with favorable disease features. Among durable responders with available baseline cytogenetic risk status, 71.4% had at least 1 high-risk cytogenetic feature, and 4 of 7 had 2 or more; 50.0% of durable responders were refractory to daratumumab (Darzalex).

Biomarker analyses showed that durable responders had higher CD4-positive naive T-cell levels at apheresis (P = .036) and higher levels of CAR-positive CD4-positive central memory T cells at peak expansion (P = .019) than patients who progressed or died of progressive disease before 5 years. According to the investigators, these 2 covariates were previously linked with prolonged PFS in CARTITUDE-4 and with long-term remission beyond 5 years after infusion in CARTITUDE-1.

What did the long-term safety analysis show?

Since the prior CARTITUDE-2 report at 30 months of follow-up, 25.0% of patients developed a second primary malignancy that investigators reported to not be related to the CAR T-cell therapy. These comprised acute myeloid leukemia, breast cancer, prostate cancer, basal cell carcinoma, stage 0 malignant melanoma (melanoma in situ), and squamous cell carcinoma, with 1 case of each; 1 patient had 2 second primary malignancies.

No new cases of CAR T-cell–related neurotoxicity occurred during long-term follow-up, including no new cases of cranial nerve palsies or parkinsonism. Two patients (10%) died since the previous report, 1 (5%) of whom died of an AE.

References

1. Cohen AD, Mateos MV, Cohen YC, et al. Long-term (≥5-year) remission and survival with ciltacabtagene autoleucel in relapsed/refractory multiple myeloma with 1-3 prior lines of therapy: CARTITUDE-2 cohort A. Presented at: 2026 International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Poster PA-288.
2. 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 September 25, 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
3. CARVYKTI - CARTITUDE-2 study (Cohort A) - use in progressive multiple myeloma after 1-3 prior lines of therapy. Johnson&Johnson. Updated September 28, 2026. Accessed September 29, 2026. https://www.jnjmedicalconnect.com/products/carvykti/medical-content/carvykti-cartitude2-study-cohort-a-use-in-progressive-multiple-myeloma-after-13-prior-lines-of-the#Hillengassetal2023main
4. Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at lease one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed September 29, 2026. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
5. Ryan C. Longer-term data continue to support earlier integration of CAR T-cell therapy in R/R myeloma. OncLive. Published August 14, 2026. Accessed September 25, 2026. https://www.onclive.com/view/longer-term-data-continue-to-support-earlier-integration-of-car-t-cell-therapy-in-r-r-myeloma