FDA Approval Sought for Cilta-Cel in Relapsed/Refractory Multiple Myeloma in Adults


Ciltacabtagene autoleucel was recently said to be a new standard-of-care for relapsed or refractory multiple myeloma. Soon, it may be an FDA-approved therapy.

  • The FDA will conduct a regular review of an approval application for ciltacabtagene autoleucel (cilta-cel; Carvykti) in a subset of patients with relapsed or refractory multiple myeloma (RRMM).
  • Progression-free survival (PFS) events in CARTITUDE-4 has surpassed 15.9 months.

A biologics license application (BLA) has been submitted to the FDA for cilta-cel, a potential treatment option for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 1 prior line of therapy, including a proteasome inhibitor, an immunomodulatory agent, and are refractory to lenalidomide (Revlimid).1

The announcement of the BLA comes on the heels of a presentation of positive data at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, which come from the phase 3 CARTITUDE-4 study (NCT04181827). In the study, treatment with cilta-cel led to a significant improvement in PFS over standard-of-care (SOC) pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in patients with lenalidomide-refractory multiple myeloma who received 1 to 3 prior lines of therapy.

“We are focused on advancing [cilta-cel] in the treatment of multiple myeloma, including for patients with relapsed or refractory disease, where we hope to intervene earlier with the goal of transforming outcomes for patients,” said Peter Lebowitz, MD, PhD, Global Therapeutic Area head, Oncology, Janssen Research & Development, LLC, in a press release. “We look forward to collaborating with the FDA on the review of this application and continuing to bring [cilta-cel] to patients who are candidates for this CAR T therapy.”

At a median follow-up of 15.9 months (range, 0.1-27) in the study, patients in the cilta-cel arm (n = 208) had a median PFS that was not yet reached (NR; 95% CI, 22.8 months-not estimable [NE]) compared with 11.8 months (95% CI, 9.7-13.8) in the SOC arm (n = 211; HR, 0.26; 95% CI, 0.18-0.38; P < .0001). The 12-month PFS rate was 76% in the cilta-cel arm vs 49% in the SOC arm.

Blood cells in a bone marrow biopsy, AI Generative | Image Credit: © Катерина Євтехова - www.stock.adobe.com

Image Credit: © Катерина Євтехова - www.stock.adobe.com

The PFS benefit was observed across all prespecified subgroups, which includes patients who had 1 prior line of treatment (HR, 0.35; 95% CI, 0.19-0.66) and patients who had 2 or 3 prior lines of therapy (HR, 0.24; 95% CI, 0.16-0.37).

The secondary end points explored in CARTITUDE-4 were complete response (CR) or better rate, overall response rate (ORR), minimal residual disease (MRD) negativity, overall survival (OS), safety, and patient-reported outcomes (PROs). All secondary end point data had reached maturity at the time of the ASCO presentation, except for OS and PROs.

Cilta-cel achieved an ORR of 84.6% compared with 67.3% in the SOC arm (odds ratio, 3.0; 95% CI, 1.8-5.0; < .0001). Among those treated with cilta-cel, 58.2% of patients had a stringent CR (sCR), 14.9% had a CR, 8.2% had a very good partial response (VGPR), and 3.4% had a PR. Among those treated with SOC, the sCR, CR, VGPR, and PR rates were 15.2%, 6.6%, 23.7%, and 21.8%, respectively.

The median duration of response (DOR) was not reached in the cilta-cel arm compared with 16.6 months (95% CI, 12.9-NE) in the SOC arm. The 12-month DOR rates observed were 84.7% (95% CI, 78.1%-89.4%) with cilta-cel vs 63.0% (95% CI, 54.2%-70.6%) with SOC.

In the intent-to-treat population (n = 419), 60.6% of patients who received cilta-cel experienced MRD negativity at a 10-5 sensitivity vs 15.6% of patients given SOC (odds ratio, 8.7; P < .0001). Of the MRD-evaluable patients in the cilta-cel arm (n = 144), 87.5% achieved MRD negativity compared with 32.7% of the SOC arm (n = 101).

At data cutoff, the estimated HR for OS favored the cilta-cel arm vs the SOC arm (HR, 0.78; 95% CI, 0.5-1.2; P = .26).

In terms of safety, patients in both study arms experienced at least 1 any-grade adverse effect (AE), including 96.6% of the cilta-cel arm vs 94.2% of the SOC arm. Any-grade serious AEs occurred in 44.2% of patients in the cilta-cel arm compared with 38.9% of those in the SOC arm. Grade 3/4 serious AEs occurred in 32.2% vs 33.7%, respectively.

The most common any-grade hematologic AEs in the cilta-cel arm vs the SOC arms were neutropenia (89.9% v 85.1%), anemia (54.3% v 26.0%), thrombocytopenia (54.3% v 31.3%), and lymphopenia (22.1% v 13.9%). Grade 3/4 hematologic AEs in the cilta-cel arm vs the SOC arms were neutropenia (89.9% v 82.2%), anemia (35.6% v 14.4%), thrombocytopenia (41.3% v 18.8%), and lymphopenia (20.7% v 12.0%).

Any-grade infections occurred 62.0% of the cilta-cel arm compared with 71.2% of SOC arm, and grade 3/4 infections were reported in 26.9% and 24.5%, respectively. The most common any-grade infections in the cilta-cel group vs the SOC group were upper respiratory tract (18.8% v 26.0%), lower respiratory tract (9.1% v 17.3%), and COVID-19 (13.9% v 26.4%). The grade 3/4 infections observed in the cilta-cel arm vs the SOC arm included upper respiratory tract (1.9% v 1.9%), lower respiratory tract (4.3% v 3.8%), and COVID-19 (2.9% v 5.8%).

“We'll continue to follow-up these patients over time to see the effect of cilta-cel on this patient population as well to compare in the standard of care. Further, we will look into different subgroups. We’ll look at the quality-of-life data and the biomarker analysis to understand the long-term effect of cilta-cel in this patient population,” said Binod Dhakal, MD, MS, associate professor of Medicine, at the Medical College of Wisconsin, Division of Hematology, in an interview with Targeted Oncology™.


1. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of Carvykti® for the earlier treatment of patients with relapsed or refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. June 6, 2023. Accessed June 7, 2023. https://shorturl.at/flyB4

2. Dhakal B, Yong K, Harrison SJ, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. J Clin Oncol. 2023;41(suppl 17):LBA106. doi:10.1200/JCO.2023.41.17_suppl.LBA106

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