CHMP Recommends Approval of Cilta-Cel for Early Relapsed/Refractory Multiple Myeloma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of a Type II variation of ciltacabtagene autoleucel (cilta-cel; Carvykti) for the earlier-line treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI), have experienced disease progression on their previous line of therapy, and are lenalidomide (Revlimid) refractory.¹

“Early resistance to standard treatments is becoming more common in patients with lenalidomide-refractory multiple myeloma, highlighting a need for new options earlier in the course of treatment,” Edmond Chan, MBChB, MD (Res), senior director and EMEA Therapeutic Area Lead Haematology at Janssen-Cilag Limited, a Johnson & Johnson Company, stated in a press release. “Today’s recommendation from the CHMP recognizes the potential of cilta-cel to significantly improve outcomes for eligible patients with relapsed and refractory multiple myeloma, as early as after first relapse.”

The positive opinion by CHMP was supported by findings from the phase 3 CARTITUDE-4 trial (NCT04181827), which investigated the efficacy and safety of cilta-cel vs standard-of-care (SOC) pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory multiple myeloma who had received between 1 and 3 prior lines of therapy. At a median follow-up of 15.9 months (range, 0.1-27.3), the median progression-free survival was not reached in patients who received cilta-cel (n = 208) and 11.8 months in patients who received SOC (n = 211; HR, 0.26; 95% CI, 0.18-0.38; P < .001).² Moreover, 84.6% of patients in the cilta-cel arm achieved an overall response vs 67.3% of those in the SOC arm (OR, 3.0; 95% CI, 1.8-5.0). The respective rates of complete response (CR) or better and minimal residual disease (MRD) negativity were 73.1% and 60.6% in the cilta-cel arm and 21.8% and 15.6% in the SOC arm (OR for CR or better, 10.3 [95% CI, 6.5-16.4]; OR for MRD negativity, 8.7 [95% CI, 5.4-13.9]).

Regarding safety, in the cilta-cel as-treated population (n = 176), 76.1% experienced cytokine release syndrome (grade 3/4, 1.1%; grade 5, 0%), and 4.5% experienced immune effector cell–associated neurotoxicity (all grade 1/2). Furthermore, 1 patient in this population had grade 1 movement and neurocognitive symptoms, 9.1% of patients experienced cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 2.8% of patients had CAR T cell therapy–related peripheral neuropathy (grade 1/2, 2.3%; grade 3, 0.6%).

“We are committed to the advancement of cilta-cel and other immunotherapies, as we aim to improve outcomes for patients and redefine the multiple myeloma treatment paradigm,” Sen Zhuang, MD, PhD, vice president of Clinical Research and Development at Johnson & Johnson Innovative Medicine, added in the press release.¹ “Today’s milestone represents an important step forward in the treatment of this complex disease and in our ultimate goal of one day delivering a cure.”

Cilta-cel is currently approved by the European Commission under conditional marketing authorization (CMA) for adults patients with relapsed/refractory multiple myeloma who have received at least 3 prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody, and who have experienced disease progression on their latest line of therapy.³ Since the obligations of the conditional approval have now been met, the CHMP has recommended converting the CMA to a standard marketing authorization.¹

In the United States, cilta-cel is FDA approved for use in adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, including a PI, IMiD, and an anti-CD38 monoclonal antibody.⁴ Furthermore, a supplemental biologics license application has been submitted to the FDA seeking the approval of the agent for the treatment of adult patients with relapsed and lenalidomide-refractory multiple myeloma who have received at least 1 prior line of therapy, including an IMiD and a PI.⁵

References

1. Janssen receives positive CHMP opinion for Carvykti (ciltacabtagene autoleucel; cilta-cel) for treatment in earlier lines of relapsed and refractory multiple myeloma. News release. Janssen. February 23, 2024. Accessed February 23, 2024. https://www.jnj.com/media-center/press-releases/janssen-receives-positive-chmp-opinion-for-carvykti-ciltacabtagene-autoleucel-cilta-cel-for-treatment-in-earlier-lines-of-relapsed-and-refractory-multiple-myeloma#:~:text=BEERSE%2C%20BELGIUM%2C%2023%20February%202024,ciltacabtagene%20autoleucel%3B%20cilta%2Dcel
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. European Commission grants conditional approval of Carvykti (ciltacabtagene autoleucel), Janssen’s first cell therapy, for the treatment of patients with relapsed and refractory multiple myeloma. News release. Janssen. May 26, 2022. Accessed February 23, 2024. https://www.janssen.com/emea/sites/www_janssen_com_emea/files/carvykti_ec_approval_press_release.pdf
4. U.S. FDA approves Carvykti (ciltacabtagene autoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed February 23, 2024. https://www.jnj.com/media-center/press-releases/u-s-fda-approves-carvykti-ciltacabtagene-autoleucel-janssens-first-cell-therapy-a-bcma-directed-car-t-immunotherapy-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma
5. Legend Biotech announces submission of supplemental application to the U.S. FDA for expanded use of Carvykti (ciltacabtagene autoleucel). News release. Legend Biotech Corporation. June 6, 2023. Accessed February 23, 2024. https://legendbiotech.com/legend-news/legend-biotech-announces-submission-of-supplemental-application-to-the-u-s-fda-for-expanded-use-of-carvykti-ciltacabtagene-autoleucel-2/