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FDA Approves Cilta-Cel for Earlier Treatment of RRMM


Most recently, the FDA’s Oncologic Drugs Advisory Committee unanimously voted to recommend ciltacabtagene autoleucel (Carvykti; Johnson & Johnson) in patients who have received at least 1 line of treatment for relapsed/refractory multiple myeloma (RRMM).

The FDA has approved Janssen/Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel) for use as earlier treatment in patients who have relapsed/refractory multiple myeloma (RRMM) that is refractory to lenalidomide and who have received at least 1 line of treatment with a proteasome inhibitor (PI) and an immunomodulatory (IMiD) agent.1

This approval follow’s the pharma giant’s submission of a supplemental biologics license application for this indication in June of 2023, with data from the phase 3 CARTITUDE-4 study (NCT04181827) providing evidence of a significant improvement in progression-free survival (PFS),2 and the recent unanimous vote by the FDA’s Oncologic Drugs Advisory Committee to recommend the treatment for these patients.3

Cilta-cel was first approved for RRMM in March 2022, based on data from the CARTITUDE-1 (NCT03548207) phase 1b/2 trial.4

Johnson and Johnson sign | Image Credit: MichaelVi - stock.adobe.com

Data from the phase 3 CARTITUDE-4 trial show cilta-cel superior in efficacy vs current standard treatments for patients who have relapsed/refractory multiple myeloma | Image Credit: MichaelVi - stock.adobe.com

"Carvykti demonstrated remarkable efficacy as a personalized, one-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, and second study author in a statement announcing the FDA's decision. "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."

CARTITUDE-4 is an ongoing phase 3 trial—and the first trial—comparing the safety and efficacy of cilta-cel in 208 patients against 2 standard-of-care (SOC) treatment regimens in 211 patients5,6:

  • Oral pomalidomide 4 mg on days 1 to 14, subcutaneous (SC) bortezomib (Velcade) 1.3 mg/m2 on days 1, 4, 8, and 11 for cycles 1 to 8 and days 1 to 8 for cycle 9 onwards,and oral dexamethasone 20 mg/d (10 mg/d if > 75 years) on days 1, 2, 4, 5, 8, 9, 11 and 12 of cycles 1 to 8 and days 1, 2, 8 and 9 for cycle 9 onwards
  • SC daratumumab 1800 mg weekly on days 1, 8, 15, and 22 of cycles 1 and 2; every 2 weeks on days 1 and 15 of cycles 3 to 6; and every 4 weeks on day 1 for cycle 7 onwards); oral pomalidomide 4 mg on days 1 to 21 for cycle 1 onwards; and oral or intravenous dexamethasone 40 mg/week (20 mg/week if > 75 years) on days 1, 8, 15, and 22 for cycle 1 onwards

The primary end point is PFS improvement in patients who have received 1 to 3 prior lines of therapy, and secondary end points are safety, overall survival, minimal residual disease negative rate, and overall response rate.2

Adverse effects considered severe or life threatening that may require immediate medical intervention include fever (100.4°F/38°C or higher), chills/shaking chills, fast/irregular heartbeat, difficulty breathing, extreme hypotension, dizziness/lightheadedness, and neurologic toxicity, such as confusion, disorientation, difficulty speaking, loss of coordination, personality changes, peripheral neuropathy, facial numbness, Guillan-Barré syndrome, immune-mediated myelitis, and prolonged and recurrent cytopenias.7,8

Initial announcement of CARTITUDE-4 meeting its PFS end point came in January of 2023,8 and was followed last year by several notable announcements:

  • At the European Hematology Association 2023 Congress, initial phase 3 results demonstrated a median PFS of 11.8 months in the standard-of-care (SOC) arm vs not reached for cilta-cel, with 76% of patients in the study arm achieving PFS at 12 months vs 29% in the SOC arm5
  • A retrospective analysis of CARTITUDE-1 data in August 2023 demonstrated comparable outcomes between patients who did or did not under prior allogeneic stem cell transplant9
  • During the 20th International Myeloma Society Annual Meeting in October 2023, an intention-to-treat analysis showed 89.6% (95% CI, 78.4%-95.2%) and 88.5% (95% CI, 80.7%-93.3%) PFS rates in patients with standard or high cytogenetic risks, respectively10
  • At the 2023 American Society of Hematology Annual Meeting and Exposition, data showed patients receiving cilta-cel reported improved quality of life and symptoms vs worsening or less improvement in those who received SOC11

The current approved indication for cilta-cel is in patients with severely refractory MM who have failed at least 4 other treatments. As a chimeric antigen receptor (CAR) T-cell therapy, it uses a patient’s genetically modified white blood cells for a 1-time intravenous infusion at a target dose of 0.75 x 106 CAR-positive viable T cells/kg administered over 30 to 60 minutes.6,7 With this newest approval, the pool of patients eligible for the treatment expands; only approximately 15% of patients who have MM initially are able to receive fifth-line therapy.12

Cilta-cel also has received conditional marketing approval from the European Commission in May 2022 for use in patients with RRMM who have disease progression despite receiving at least 3 prior lines of therapy (an IMiD, a PI, and an anti-CD38 antibody).3


1. 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. PR Newswire. April 5, 2024. Accessed April 6, 2024. https://www.prnewswire.com/news-releases/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-302109706.html#:~:text=HORSHAM%2C%20Pa.%2C%20April%205,received%20at%20least%20one%20prior

2. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of Carvykti for the earlier treatment of patients with relapsed or refractory multiple myeloma. News release. Johnson & Johnson. June 6, 2023. Accessed April 2, 2024. https://www.jnj.com/media-center/press-releases/janssen-submits-supplemental-biologics-license-application-to-u-s-fda-seeking-approval-of-carvykti-for-the-earlier-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma

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. PR Newswire. March 15, 2024. Accessed April 2, 2024. https://www.prnewswire.com/news-releases/us-fda-oncologic-drugs-advisory-committee-recommends-carvykti-ciltacabtagene-autoleucel-for-the-earlier-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma-302090580.html

4. Caffrey M. FDA approves cilta-cel to treat R/R multiple myeloma. The American Journal of Managed Care®. March 1, 2022. Accessed April 2, 2024. https://www.ajmc.com/view/fda-approves-cilta-cel-to-treat-r-r-multiple-myeloma

5. Mattina C. Phase 3 CARTITUDE-4 results show superiority of cilta-cel in MM. The American Journal of Managed Care. June 10, 2023. Accessed April 2, 2024. https://www.ajmc.com/view/phase-3-cartitude-4-results-show-superiority-of-cilta-cel-in-mm

6. 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. Updated March 27, 2024. Accessed April 2, 2024. https://clinicaltrials.gov/study/NCT04181827

7. Carvykti (ciltacabtagene autoleucel). Janssen/Johnson & Johnson. Accessed April 2, 2024. https://www.carvykti.com/

8. Janssen announces unblinding of phase 3 CARTITUDE-4 study of Carvykti as primary endpoint met in treatment of patients with relapsed and refractory multiple myeloma. News release. Johnson & Johnson. January 27, 2023. Accessed April 2, 2024. https://www.jnj.com/media-center/press-releases/janssen-announces-unblinding-of-phase-3-cartitude-4-study-of-carvykti-cilta-cel-as-primary-endpoint-met-in-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma

9. McNulty R. Study suggests CAR T-cell therapy safe, effective after allo-SCT in multiple myeloma. The American Journal of Managed Care. August 26, 2023. Accessed April 2, 2024. https://www.ajmc.com/view/study-suggests-car-t-cell-therapy-safe-effective-after-allo-sct-in-multiple-myeloma

10. Flaherty C. Cilta-cel leads to high PFS rates in patients with multiple myeloma and poor prognostic features. OncLive®. September 30, 2023. Accessed April 2, 2024. https://www.onclive.com/view/cilta-cel-leads-to-high-pfs-rates-in-patients-with-multiple-myeloma-and-poor-prognostic-features

11. McNulty R. ASH abstracts show PRO improvements, long-term efficacy of cilta-cel in MM. The American Journal of Managed Care. December 24, 2023. Accessed April 2, 2024. https://www.ajmc.com/view/ash-abstracts-show-pro-improvements-long-term-efficacy-of-cilta-cel-in-mm

12. Fonseca R, Usmani SZ, Mehra M, et al. Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. BMC Cancer. 2020;20(1):1087. doi:10.1186/s12885-020-07503-y

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