CARTITUDE-2: Cilta-cel ± Len maintenance for MM with suboptimal response to ASCT

The Multiple Myeloma Hub spoke with María-Victoria Mateos, University Hospital of Salamanca, ES. We asked about the latest findings from the updated follow-up of CARTITUDE-2 Cohort D. 

During this interview, Mateos discussed the latest outcomes from the phase II CARTITUDE-2, multicohort study evaluating ciltacabtagene autoleucel (Cilta-cel) across various clinical settings of unmet need. She covered the updated follow-up data (40.2 months) from Cohort D from the trial, which were presented at the 22nd IMS Annual Meeting (September, 17–20, 2025), investigating Cilta-cel + lenalidomide (Len) maintenance in patients with newly diagnosed multiple myeloma (NDMM) who achieved less than a complete response (CR) after autologous stem cell transplantation (ASCT) as first-line therapy (N = 17). Mateos highlighted the deep and durable responses to treatment, including achievement of measurable residual disease (MRD) negativity, and noted that no new safety signals were reported with the longer follow-up. She concluded that the benefit–risk ratio of Cilta-cel continues to be favorable for this patient population. 

Key learnings

• As of February 2025, 17 patients had received Cilta-cel in Cohort D of CARTITUDE-2, with a median follow-up of 40.2 months. At baseline:
  • Median time from initial diagnosis to enrollment was less than 1 year.
  • The majority of patients had been treated with proteasome inhibitors only; three patients had received prior anti-CD38 monoclonal antibodies.
• In the 12 patients who received continuous Len maintenance after Cilta-cel, Len was given at a dose of 10 mg daily upon adequate hematological recovery. The median time to initiation of Len maintenance was 51 days, with a median duration of 696.5 days, and the number of cycles ranged from 3 to 34, with a median overall relative dose intensity of 93.4%.
• Objective response rate (ORR; defined as the proportion of patients who achieved ≥ partial response per the International Myeloma Working Group criteria) was achieved by 94.1% of patients treated with Cilta-cel; all of these patients had stringent CR.
• Of the 16 responders, 14 were alive and in ≥CR (follow-up range, 13.4–55.9 months), including 1 patient lost to follow-up on Day 407.
  • One patient progressed and died of MM at 11 months.
  • One patient died in a motor vehicle accident while in response at 42 months.
• Overall, of 16 evaluable patients MRD negativity was achieved in 81.3%; MRD negative ≥CR rate was 72.7% at 24 months and 75.0% at 36 months.
• At 3 years, progression-free survival and overall survival were >90%.
• No new safety signals were observed in the longer follow-up, with six patients experiencing CAR T-cell therapy-related neurotoxicities; in addition, there were no cases of parkinsonism or Guillain-Barré syndrome and no new second primary malignancies.
• Overall, the benefit–risk ratio of Cilta-cel continues to be favorable for patients with NDMM with less than a CR after first-line ASCT.
• There is a need for a randomized, phase III trial to further evaluate the role of Len maintenance after CAR T-cell therapy in patients with MM. 

This educational resource is independently supported by Legend Biotech. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.