FDA Approves Cilta-Cel for Earlier Lines of R/R Multiple Myeloma

• The FDA has approved ciltacabtagene autoleucel (cilta-cel; Carvytki) for the treatment of patients with relapsed/refractory (R/R) multiple myeloma who have received at least 1 prior line of therapy and are refractory to lenalidomide.
• Cilta-cel had been approved for patients who had previously received at least 4 prior lines of therapy.
• In March 2024, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11 to 0 that the benefits of cilta-cel outweigh the risks for this patient population.

The FDA approved cilta-cel, a chimeric antigen receptor (CAR) T-cell therapy, for R/R multiple myeloma that has been treated with at least 1 prior line of therapy, including a proteasome inhibitor (PI) and immunomodulatory (IMiD) agent and is refractory to lenalidomide.¹

The approval is supported by data from the phase 3 CARTITUDE-4 study (NCT04181827) that were originally presented at the 2023 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine. At a median follow-up of 15.9 months (range, 0.1-27.3), the median progression-free survival (PFS) was not reached in the cilta-cel arm vs 11.8 months in the standard-of-care arm (HR, 0.26; 95% CI, 0.18-0.38; P <.001). PFS at 12 months was 75.9% (95% CI, 69.4%-81.1%) and 48.6% (95% CI, 41.5%-55.3%) in the cilta-cel vs standard of care arms, respectively.²

Cilta-cel was approved in February 2022 for patients with R/R multiple myeloma who had received at least 4 prior lines of therapy, including a PI, IMiD, and anti-CD38 antibody.³ In March 2024, the FDA’s ODAC met to discuss data from CARTITUDE-4. The Committee unanimously agreed that, despite the safety risks, the benefits of cilta-cel outweigh the risks in this earlier line of treatment.⁴

“​​We saw cilta-cel significantly reduced the risk of disease progression or death vs standard of care by 74%. Cilta-cel led to significantly higher rates of response and default response compared with standard of care,” said Binod Dhakal, MD, MS, assistant professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, in an interview with Targeted Oncology^TM. “These results suggest cilta-cel is highly effective and provides superior efficacy responses compared with standard of care in the study.”

In the cilta-cel vs standard-of-care arms, 84.6% and 67.3% of patients had an overall response, 73.1% and 21.8% had a complete response or better, and 60.6% and 15.6% had an absence of minimal residual disease. Overall survival data are not fully mature but continue to strengthen.⁴

Regarding safety, 39 patients and 46 patients across both arms died (HR, 0.78; 95% CI, 0.5-1.2), and most patients experienced a grade 3 or 4 adverse event during treatment. Among 176 patients treated with cilta-cel, 134 (76.1%) had cytokine release syndrome (CRS), 1.1% of which was grade 3 or 4. No grade 5 CRS was observed.

Also in this group, 8 (4.5%) patients had immune effector cell-associated neurotoxicity syndrome, all of which were grade 1 or 2. Further, 1 patient had movement and neurocognitive symptoms deemed grade 1, 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had peripheral neuropathy that was related to CAR T-cell therapy (grade 1 or 2, 2.3%; grade 3, 0.6%).⁴

REFERENCES:

1. 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 April 5, 2024. https://tinyurl.com/43znj9t2

2. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379

3. U.S. FDA Oncologic Drugs Advisory Committee recommends CARVYKTI® (ciltacabtagene autoleucel) for the earlier treatment of patients with relapsed or refractory multiple myeloma. News release. Johnson & Johnson. March 15, 2024. Accessed April 2, 2024. https://tinyurl.com/yc2z5khw

4. Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA. March 15, 2024. Accessed April2, 2024. https://tinyurl.com/bdhcn4ey