FDA Approves Cilta-Cel for Treatment of Relapsed, Refractory Multiple Myeloma

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The indication is for adult patients with multiple myeloma who are refractory to lenalidomide and have previously received at least 1 line of therapy.

The FDA has approved ciltacabtagene autoleucel (cilta-cel; Carvykti; Janssen Biotech, Inc.) for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously received at least 1 line of therapy (eg, proteasome inhibitor and immunomodulatory agent) and are refractory to lenalidomide. The approval follows positive results from the phase 3 CARTITUDE-4 trial (NCT04181827).1

FDA web browser -- Image credit: Postmodern Studio | stock.adobe.com

Image credit: Postmodern Studio | stock.adobe.com

Cilta-cel is a BCMA-directed, genetically modified autologous T-cell immunotherapy that reprograms the patient’s T-cells with a transgene encoding chimeric antigen receptor (CAR) that eliminates BCMA-expressing cells. In addition, the CAR protein features 2 BCMA-targeting single domains which target B-cell maturation antigen (BCMA), and upon binding to the cells, CAR promotes T-cell activation, expansion, and elimination of target cells. With this approval, cilta-cel is the first and only BCMA-targeted therapy to be approved by the FDA for the treatment of patients with multiple myeloma as early as first relapse.1

Previously, cilta-cel received an FDA approval for the treatment of adults with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy (eg, proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody). Cilta-cel is now approved for the second-line treatment of adult patients with relapsed or refractory multiple myeloma who received at least 1 prior line of therapy. The treatment was also granted a unanimous FDA Oncologic Drugs Advisory Committee recommendation in support of the new indication.1

About the Trial

Trial Name: A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4)

ClinicalTrials.gov ID: NCT04181827

Sponsor: Janssen Research & Development, LLC

Completion Date (Estimated): June 30, 2027

CARTITUDE-4 is the first international, randomized, open-label phase 3 study that evaluated the efficacy and safety of cilta-cel compared with pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd) in 419 adult patients with relapsed multiple myeloma. The enrolled patients had also received 1 to 3 prior lines of therapy and are refractory to lenalidomide. Patients were randomly assigned to receive either cilta-cel (n = 208) or PVd or DPd (standard-care group: n = 211).1,3

The study’s primary end point was progression-free survival (PFS) until the end of the study or up to 6 years, and the secondary end points included overall minimal residual disease (MRD) negativity, complete response (CR) or stringent complete response rate, overall survival, and overall response rate, among others.1,2

At a median follow-up of 15.9 months (range: 0.1-27.3 months), the median PFS was not met in the cilta-cel group, and median PFS was 11.8 months in the 2 standard-care groups; however, PFS at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. Further, patients who were treated with cilta-cel also had a better overall response than those treated with standard-care regimens (84.6% vs 67.3%, respectively), a CR or better (73.1% vs 21.8%), and an absence of MRD (60.6% vs 15.6%).3

“[Cilta-cel] demonstrated remarkable efficacy as a personalized, 1-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” said Binod Dhakal, MD, associate professor, Medical College of Wisconsin, Division of Hematology and Oncology, in a press release.1

“With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease,” said Dhakal in the press release.1

The adverse effects (AEs) reported by study participants who were treated with cilta-cel include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, movement and neurocognitive symptoms, cranial nerve palsy, and peripheral neuropathy related to CAR-T treatment. AEs were of differing severities; however, grade 5 occurrences were not reported by patients. Further, the most common grade 3 or 4 laboratory AEs were lymphopenia, neutropenia, decreases in white blood cells, thrombocytopenia, and anemia.1,3

“This milestone underscores our commitment to improve outcomes for patients and transform the treatment of multiple myeloma with [cilta-cel],” said Jordan Schecter, MD, vice president, disease area leader, multiple myeloma, Johnson & Johnson Innovative Medicine, in the press release. “We are proud to bring an important, highly effective immunotherapy that has demonstrated a favorable benefit/risk profile to physicians and patients for the earlier treatment of relapsed or refractory multiple myeloma, and we look forward to building on this latest milestone as we continue to focus on our ultimate goal of delivering a cure for multiple myeloma.”1

References
1. Johnson & Johnson. 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. April 6, 2024. Accessed April 10, 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
2. A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4).ClinicalTrials.gov identifier: NCT04181827. Updated March 27, 2024. Accessed April 10, 2024. https://www.clinicaltrials.gov/study/NCT04181827
3. San-Miguel, J, Dhakal, B, Yong, K, et al. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. N Eng J Med. 2023;389:335-347. doi:10.1056/NEJMoa2303379
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