Carvykti Significantly Improves Overall Survival in Relapsed Multiple Myeloma in Phase III Trial

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Carvykti (ciltacabtagene autoleucel) was found to produce a significant improvement in overall survival (OS) in patients with relapsed or lenalidomide-refractory multiple myeloma, according to long-term data from the Phase III CARTITUDE-4 (NCT04181827) trial.^1,2

The BCMA-directed, genetically modified autologous T-cell immunotherapy was found to lower the risk of death by 45% compared to standard treatments consisting of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). In achieving this result, Carvykti becomes the first and only cell therapy to show an OS benefit compared with standard treatments as early as the second line in treating lenalidomide-refractory multiple myeloma.

“The three-year follow-up data from the Phase III CARTITUDE-4 study show a statistically significant and clinically meaningful improvement in overall survival and quality-of-life measures with Carvykti versus standard therapies—meaningful results that have the potential to transform the multiple myeloma treatment landscape,” study investigator Binod Dhakal, MD, MS, associate professor of Medicine at the Medical College of Wisconsin, Division of Hematology, said in a press release. “This adds to the growing body of data reinforcing the promise of a single infusion of Carvykti, which, in addition to demonstrating a significant [OS] benefit, also offers patients the opportunity of a period free from multiple myeloma treatment as early as second line.”¹

In March 2024, the FDA Oncologic Drugs Advisory Committee (ODAC) recommended Carvykti in earlier lines of treatment for adults with relapsed or refractory multiple myeloma who received at least one line of therapy—including a proteasome inhibitor and an immunomodulatory agent—and who are refractory to lenalidomide. ODAC voted 11-0 in favor of Carvykti based on data from CARTITUDE-4, which showed an encouraging risk-benefit profile.³

The global, randomized, controlled CARTITUDE-4 compared Carvykti with PVd or DPd in lenalidomide refractory patients. Investigators randomly assigned 208 patients to receive Carvykti and 211 patients to receive the standard therapies.⁴

Data at the 30-month follow-up showed a 76% OS rate in the Carvykti cohort compared to 64% in the standard therapies cohort. At a median follow-up of 34 months, median OS in both the Carvykti cohort and the standard therapies cohort was not reached (95% Confidence Interval [CI], not estimable [NE] – NE) and (95% CI, 37.75 months – NE) (Hazard Ratio [HR], 0.55; 95% CI, 0.39-0.79; P=0.0009).

Patients in the Carvykti cohort experienced a 45% reduction in the risk of death compared to the standard therapies cohort. Median progression-free survival (PFS) was not reached in the Carvykti cohort (95% CI, 34.50 months – NE) compared with 11.79 months (95% CI, 9.66-14.00) in the standard therapies cohort.

Further, the Carvykti cohort showed a 77% complete response or better, with an 85% overall response rate, as well as 62% minimal residual disease (MRD) negativity (10^-5) and 57% MRD-negativity (10^-6) vs. patients in the standard therapies cohort (18.5%, 9% respectively). Median duration of response was not reached (95% CI, NE-NE) in the Carvykti cohort compared to 18.7 months (95% CI, 12.9-23.7) in the standard therapies cohort.

In terms of safety, the profile of Carvykti compared with standard therapies was consistent with findings from prior trials. Across both cohorts, 97% of patients experienced grade 3/4 treatment-emergent adverse events, the most frequently reported of which was cytopenia. Treatment-emergent infections were reported by 64% of patients in the Carvykti cohort compared with 76% of patients in the standard therapies cohort.

“Carvykti is the first and only cell therapy approved for the treatment of patients with myeloma as early as second line, and now also the first and only cell therapy to improve overall survival and demonstrate improved patient quality-of-life outcomes versus standard therapies for patients with lenalidomide-refractory multiple myeloma,” Jordan Schecter, MD, VP, Disease Area Leader, Multiple Myeloma, Innovative Medicine, Johnson & Johnson, said in a press release.¹

References

1. CARVYKTI® is the first and only cell therapy to significantly extend overall survival versus standard therapies for patients with multiple myeloma as early as second line. News release. Johnson & Johnson. September 27, 2024. Accessed September 30, 2024. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-cell-therapy-to-significantly-extend-overall-survival-versus-standard-therapies-for-patients-with-multiple-myeloma-as-early-as-second-line

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. Updated September 19, 2024. Accessed September 30, 2024. https://www.clinicaltrials.gov/study/NCT04181827?intr=Cilta-cel&rank=3

3. U.S. FDA Oncologic Drugs Advisory Committee recommends CARVYKTI® (ciltacabtagene autoleucel) for the earlier treatment of patients with relapsed or refractory multiple myeloma. Johnson & Johnson. March 15, 2024. Accessed September 30, 2024. https://www.jnj.com/media-center/press-releases/u-s-fda-oncologic-drugs-advisory-committee-recommends-carvykti-ciltacabtagene-autoleucel-for-the-earlier-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma

4. Binod Dhakal et al,. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. JCO 41, LBA106-LBA106(2023). DOI: 10.1200/JCO.2023.41.17_suppl.LBA106.