Carvykti Significantly Boosts Survival, MRD Negativity in Relapsed Multiple Myeloma

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The latest results from Phase III CARTITUDE-4 trial (NCT04181827) show that Carvykti (cilta-cel; Johnson & Johnson) significantly improved minimal residual disease (MRD) negativity rates, progression-free survival (PFS), and overall survival (OS) compared to standard treatments in patients with relapsed or refractory multiple myeloma who are lenalidomide-refractory and previously received one to three lines of therapy, including a proteasome inhibitor (PI).^1,2 These findings follow data from CARTITUDE-4 released in September that show Carvykti, a BCMA-directed, genetically modified autologous T-cell immunotherapy, produced a statistically significant and clinically meaningful improvement in OS and quality-of-life measures in patients with relapsed or lenalidomide-refractory multiple myeloma.³

"Carvykti has established its significant impact on overall survival and improved progression-free survival compared to standard therapies," lead investigator Rakesh Popat, MD, University College London Hospitals, NHS Foundation Trust, London, UK, said in a press release. "The MRD negativity results demonstrate deep responses compared to standard therapies for people living with multiple myeloma and further underscore the benefit of Carvykti, administered as a single infusion as early as second line."¹

Trial Design

The global, randomized, controlled CARTITUDE-4 trial is comparing Carvykti with standard treatments consisting of pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone. The trial is being conducted in three phases—screening, which is occurring up to 28 days prior to randomization, treatment, and follow-up.²

During the trial, investigators will perform assessments of patient-reported outcomes, electrocardiogram results, vital signs, and pharmacokinetics. The trial’s primary endpoint is PFS, with secondary endpoints that include safety, OS, MRD negativity rate, and overall response rate.

Safety assessments will include a review of adverse events, laboratory test results, vital signs, physical examination results, and evaluation of cardiac function, Immune Effector Cell-associated Encephalopathy and Eastern Cooperative Oncology Group performance status. The duration of the trial is expected to run approximately six years.

Investigators randomly assigned 208 patients to receive Carvykti and 211 patients to receive the standard therapies. Results show that at a median follow-up of 34 months, rates of MRD-negativity among evaluable patients were 89% in the Carvykti cohort compared to 38% in the standard therapies cohort (P<0.0001). Notably, at 2.5 years, MRD-negative complete response or better among evaluable patients in the Carvykti cohort was 52% compared to 10% in the standard therapies cohort (P<0.0001).

Carvykti was approved by the FDA in February 2022 for adults with relapsed or refractory multiple myeloma following four or more prior lines of therapy, including a PI, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.⁴ In April 2024, Carvykti became the first FDA-approved cell therapy for adults with relapsed or refractory multiple myeloma who received at least one prior line of therapy including a PI, an immunomodulatory agent, and who are refractory to lenalidomide.⁵

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-4.⁶

"We are thrilled to present the latest MRD negativity results from the CARTITUDE-4 study showing that Carvykti, the first and only cell therapy approved for the treatment of patients with multiple myeloma as early as second line, shows profound long-term remission rates, including progression-free survival and overall survival benefits," Jordan Schecter, MD, vice president, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine, said in a press release. "It is also increasingly clear that reaching MRD negativity is a key goal with CAR T therapy in myeloma, and we see that MRD rates were higher in this analysis with earlier treatment."¹

References

1. CARVYKTI® (ciltacabtagene autoleucel) demonstrated significantly higher rates of minimal residual disease (MRD) negativity compared to standard therapies in the CARTITUDE-4 study. News release. Johnson & Johnson. December 9, 2024. Accessed December 10, 2024. https://www.prnewswire.com/news-releases/carvykti-ciltacabtagene-autoleucel-demonstrated-significantly-higher-rates-of-minimal-residual-disease-mrd-negativity-compared-to-standard-therapies-in-the-cartitude-4-study-302326770.html?tc=eml_cleartime

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 December 6, 2024. Accessed December 10, 2024. https://www.clinicaltrials.gov/study/NCT04181827?intr=Cilta-cel&rank=3

3. 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. September 27, 2024. Accessed December 10, 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

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. Johnson & Johnson. February 28, 2022. Accessed December 10, 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. 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 6, 2024. Accessed December 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

6. 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 December 10, 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