Carvykti Demonstrates Clinically Meaningful Improvement in Patients with Relapsed or Lenalidomide-Refractory Multiple Myeloma After One Line of Prior Therapy

Image Credit: Adobe Stock Images/David A. Litman

Results from the second interim analysis of the Phase III CARTITUDE-4 study, which evaluated Johnson & Johnson’s (J&J) Carvykti (ciltacabtagene autoleucel; cilta-cel) for patients with relapsed or lenalidomide-refractory multiple myeloma after one prior line of therapy showed that the treatment achieved a statistically significant and clinically meaningful improvement in overall survival (OS) compared to standard therapies such as omalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).¹

“Carvykti, a one-time infusion, is now the first cell therapy to significantly improve overall survival versus standard of care for patients with myeloma as early as second line,” said Jordan Schecter, MD, VP, disease area leader, multiple myeloma, Johnson & Johnson Innovative Medicine, in a press release. “As we continue to strive to change outcomes and advance care for every person living with multiple myeloma, we’re excited to share these results, which add to the growing body of evidence across our portfolio of differentiated, complementary therapies that attack the disease in different ways throughout the course of a patient’s journey.”

CARTITUDE-4 was the first randomized Phase 3 study evaluating the efficacy and safety of Carvykti, comparing it to standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma. The trial enrolled 419 patients that had previously undergone one prior treatment. The primary endpoint of the study was progression-free survival (PFS); safety, OS, minimal residual disease negative rate and overall response rate are secondary endpoints. Updated data is expected to be presented at a later date for submission to regulatory authorities globally.^1,2

J&J warned that in the trial, there was a numerically higher percentage of early deaths in patients randomized to the Carvykti treatment arm compared to the control arm, with a 14% death rate after the first 10 months of treatment compared to 12% in the control arm. Of the 29 deaths in the Carvykti arm, 19 occurred after infusion, including 3 due to disease progression and 16 due to adverse events (AEs). The most common AEs were a result of infections. Additional AEs included cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/ macrophage activation syndrome, and hypogammaglobulinemia.¹

According to the Leukemia & Lymphoma Society, most myeloma patients will experience relapse and/or a refractory disease state. As a result, treatment can be affected by factors such as previous therapy, rate of relapse, patient health, and genetic abnormalities.³

“In some instances, if the patient had a good response to a drug or combination of drugs initially, that treatment option may be repeated,” reported the Leukemia & Lymphoma Society. “Trying one or more of the other therapies that are typically used in initial treatment is another option.”

Current treat options include but aren’t limited to Velcade, Revlimid, Kyprolis, Darzalex, Darzalex Faspro, Empliciti, Talvey, and a number of combination treatments.³

“The use of high-dose chemotherapy followed by autologous stem cell transplantation may also be an option for some relapsed/refractory myeloma patients, who have either not been treated with a transplant before or who had a good durable response to a prior transplant,” continued the Leukemia & Lymphoma Society.

In 2024, the American Cancer Society estimated that 35,780 new cases of multiple myeloma will be diagnosed in the United States, with 12,540 people dying. The likelihood of getting it is about 1 in 103 for men and about 1 in 131 for women, but risk could be higher or lower depending on an individual’s risk factors.⁴

References

1. CARVYKTI® (ciltacabtagene autoleucel) achieved statistically significant and clinically meaningful improvement. Johnson & Johnson. July 2, 2024.Accessed July 2, 2024. https://www.jnj.com/media-center/press-releases/carvykti-ciltacabtagene-autoleucel-achieved-statistically-significant-and-clinically-meaningful-improvement

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). Accessed July 2, 2024. https://www.clinicaltrials.gov/study/NCT04181827?intr=Cilta-cel&rank=3

3. REFRACTORY AND RELAPSED. Leukemia & Lymphoma Society. Accessed July 2, 2024. https://www.lls.org/myeloma/treatment/refractory-and-relapsed

4. Key Statistics About Multiple Myeloma. American Cancer Society. Accessed July 2, 2024. https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statistics.html