European Commission Approves Cilta-Cel for R/R Myeloma After at Least 1 Prior Line of Therapy

The European Commission (EC) has approved ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of patients with relapsed/refractory multiple myeloma who have received 1 or more prior lines of therapy, including an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI); have progressed on their last line of therapy; and are refractory to lenalidomide (Revlimid).¹

The expanded indication for cilta-cel was based on findings from the phase 3 CARTITUDE-4 trial (NCT04181827), which demonstrated that at a median follow-up of 15.9 months (range, 0.1-27.3), treatment with cilta-cel reduced the risk of progression or death by 74% vs standard therapies in patients with relapsed/refractory disease who had received 1 to 3 prior lines of therapy (HR, 0.26; 95% CI, 0.18-0.38). The median progression-free survival (PFS) was not yet reached in the cilta-cel arm vs 11.8 months (95% CI, 9.7-13.8) in the standard of care (SOC) arm. The 12-month estimated PFS rates were 76% (95% CI, 69%-81%) with cilta-cel vs 49% (95% CI, 42%-55%) with SOC.^1,2

“Patients with lenalidomide-refractory multiple myeloma tend to experience early resistance to standard treatments, and their disease worsens exponentially with each additional line of therapy,” Jesús San Miguel, MD, PhD, a professor of medicine-hematology and director of Clinical & Translational Medicine at Universidad de Navarra in Spain, stated in a news release.¹ “A single infusion of cilta-cel has been shown to significantly lower the risk of progression or death compared to current treatment options, as early as after first relapse.”

In CARTITUDE-4, 419 patients were randomly assigned to receive either apheresis followed by bridging therapy, lymphodepletion, and cilta-cel (n = 208) or standard pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone or daratumumab (Darzalex) plus pomalidomide and dexamethasone (n = 211).

Patients who received cilta-cel achieved an overall response rate of 84.6%, including a complete response or better rate of 73.1%.² These respective values were 67.3% and 21.8% among patients who received SOC. The rates of minimal residual disease negativity were 60.6% and 15.6% in the cilta-cel and SOC arms, respectively. At a median follow-up of 28.7 months, the median overall survival was not evaluable (NE) in both the cilta-cel (95% CI, NE-NE) and SOC (95% CI, 34 months-NE) arms, with a trend favoring cilta-cel (HR, 0.57; 95% CI, 0.4-0.8).¹

Adverse effects (AEs) were evaluated among patients in the safety population, which consisted of 208 patients in each arm. Hematologic AEs comprised the most common grade 3/4 AEs in both arms, including neutropenia (cilta-cel, 90%; SOC, 82%), thrombocytopenia (41%; 19%), and anemia (36%; 14%). Serious AEs occurred in 44.2% of patients in the cilta-cel arm vs 38.9% of those in the SOC arm. Infections were observed in 62% and 71% of patients in the cilta-cel and SOC arms, respectively. Thirty-nine deaths occurred in the cilta-cel arm compared with 46 deaths in the SOC arm. Among these deaths, 10 in the cilta-cel arm and 5 in the SOC arm were from treatment-emergent AEs. Furthermore, cytokine release syndrome occurred in 76.1% of the patients who received cilta-cel (n = 176), 1.1% of which was grade 3/4.

“Cilta-cel is a highly innovative, personalized cell therapy that continues to deliver positive outcomes in patients in need of new therapeutic options,” Edmond Chan, MBChB, MD (Res), the EMEA Therapeutic Area Lead for Haematology at Janssen-Cilag Limited, a Johnson & Johnson Company, added in the news release. “Today’s approval marks important progress for eligible patients with multiple myeloma, who may now benefit from treatment with cilta-cel earlier in their treatment pathway, where it has the potential to transform outcomes and change the trajectory of their disease.”

The EC also approved the conversion of the conventional marketing authorization for cilta-cel to a standard marketing authorization since the requirements of the conditional approval have now been met.

“Our ambition is to progress the science to address patients’ needs at each stage of this complex disease,” Jordan Schecter, MD, vice president and disease area leader of Multiple Myeloma at Johnson & Johnson Innovative Medicine, noted in the news release. “Cilta-cel is an important part of how we are working to redefine multiple myeloma and ultimately achieve sustained remissions for patients. We are determined to get in front of cancer, and today’s approval represents an important step forward in achieving this goal.”

Previously, on April 5, 2024, the FDA approved cilta-cel for the treatment of adult patients with relapsed/refractory multiple myeloma who have received 1 or more prior lines of therapy, including an IMiD and a PI, and who are refractory to lenalidomide.³

References

1. Carvykti (ciltacabtagene autoleucel; cilta-cel) is the first BCMA-targeted treatment approved by the European Commission for patients with relapsed and refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 22, 2024. Accessed April 22, 2024. https://www.janssen.com/carvyktirv-ciltacabtagene-autoleucel-cilta-cel-first-bcma-targeted-treatment-approved-european
2. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. New Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2304479
3. 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 least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed April 22, 2024. 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