European Commission Approves Cilta-cel in R/R Multiple Myeloma

The FDA granted approval to cilta-cel for the same patient population in April 2024. The regulatory agency based its decision on data from the CARTITUDE-4 trial (NCT04181827).

The European Commission has approved ciltacabtagene autoleucel (cilta-cel; Carvykti) for adult patients with relapsed/refractory multiple myeloma previously treated with 1 or more lines of therapy including a proteasome inhibitor and an immunomodulatory agent, according to a press release from Legend Biotech Corporation.¹

Specifically, cilta-cel is also indicated for use in those who have disease progression following their last line of therapy and are refractory to lenalidomide (Revlimid).

Supporting data for the approval of cilta-cel in the European Union came from the phase 3 CARTITUDE-4 study (NCT04181827). According to findings published in The New England Journal of Medicine, the median progression-free survival (PFS) was not reached with cilta-cel compared with 11.8 months (95% CI, 9.7-13.8) in those who received standard-of-care therapy (HR, 0.26; 95% CI, 0.18-0.38; P <.001).² The 12-month PFS rate was 75.9% (95% CI, 69.4%-81.1%) vs 48.6% (95% CI, 41.5%-55.3%) in each respective treatment arm.

Regarding safety, any-grade adverse effects in the cilta-cel arm included cytokine release syndrome (76.1%) and immune effector cell-associated neurotoxicity (4.5%).

“The European Commission’s approval of [cilta-cel] has the potential to transform the treatment paradigm for patients [with] multiple myeloma by bringing our novel therapy to them earlier in the course of this incurable disease,” Ying Huang, PhD, chief executive officer at Legend Biotech, said in the press release.¹ “This approval is a testament to our innovative science and galvanizes our efforts to provide new options that will improve outcomes for patients and give hope to them and their families.”

In the CARTITUDE-4 trial, patients were assigned 1:1 to receive cilta-cel as a single infusion at a target dose of 0.75 x 10⁶ CAR-positive viable T cells/kg or standard-of-care therapy. Treatment options in the standard care arm included pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone or daratumumab (Darzalex) plus pomalidomide and dexamethasone.

The trial’s primary end point was PFS. Secondary end points included overall response rate, overall survival, and patient-reported outcomes.

Patients with 1 to 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent who were refractory to lenalidomide were eligible for enrollment on the trial. Having an ECOG performance status of 0 or 1 was an additional requirement for enrollment.

The FDA granted approval to cilta-cel for the same patient population in April 2024.³ The regulatory agency based its decision on data from the CARTITUDE-4 trial.

References

1. CARVYKTI® (ciltacabtagene autoleucel) approved by the European Commission for second-line treatment of patients with relapsed and refractory multiple myeloma. News release. Legend Biotech Corporation. April 22, 2024. Accessed April 24, 2024. https://tinyurl.com/4j6ccjy6
2. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Eng J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379
3. 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. News release. Johnson & Johnson. April 5, 2024. Accessed April 24, 2024. https://tinyurl.com/5n7zpkd9