Cilta-Cel Boosts MRD Negativity Rates Compared to Standard of Care Therapy in New Multiple Myeloma Data
The results come from patients with lenalidomide-refractory MM treated in the CARTITUDE-4 trial after 1 to 3 lines of prior therapy.
Johnson & Johnson subsidiary Janssen’s and Legend Biotech's ciltacabtagene autoleucel (cilta-cel; marketed as Carvykti) an FDA-approved BCMA-directed autologous chimeric antigen receptor T-cell (CAR-T) therapy, has produced higher rates of minimal residual disease (MRD) negativity in comparison to patients treated with standard-of-care (SOC) therapy for lenalomide-refractory multiple myeloma (MM) in newly updated data from the phase 3 CARTITUDE-4 clinical trial (NCT04181827).1 The findings were presented by study investigator Rakesh Popat, MD, an honorary associate professor at University College London Hospitals, NHS Foundation Trust, at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California.
The trial randomly assigned participants with relapsed or lenalidomide-refractory MM, who had previously been treated with 1 to 3 prior lines of therapy that included a protesome inhibitor (PI) and an immunomodulatory agent (IMiD), to receive either cilta-cel (n = 208) or SOC (n = 211), which consisted of either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). For the 145 patients treated with cilta-cel who were evaluable for MRD negativity at a threshold of 10-5, 89.0% achieved MRD negativity; on the other hand, for the 103 patients treated with SOC evaluable at this threshold, 37.9% achieved MRD negativity (OR: 13.3; P < .0001; median follow-up, approximately 34 months). For the 139 patients treated with cilta-cel who were evaluable for MRD negativity at a threshold of 10-6, 85.6% achieved MRD negativity; for the 102 patients treated with SOC who were evaluable at this threshold, 18.6% achieved MRD negativity (OR: 28.5; P < .0001). Furthermore, 69% of the patients in the cilta-cel intent to treat (ITT) population evaluable for MRD negativity at the 10-5 threshold achieved MRD negativity by 56 days posttreatment and 86% of the patients in the cilta-cel ITT population evaluable for MRD negativity at the 10-5 threshold achieved MRD negativity by 6 months posttreatment.
“Carvykti has established its significant impact on OS and improved PFS compared to standard therapies,” Popat said in a statement.2 “The MRD negativity results demonstrate deep responses compared to standard therapies for people living with MM and further underscore the benefit of Carvykti, administered as a single infusion as early as second line.”
Popat also highlighted that as of the data cutoff, 51.7% of evaluable patients treated with cilta-cel achieved an MRD-negative (10-5) complete response (CR) or better lasting at least 12 months, while less than 9.7% of evaluable patients treated with SOC had achieved the same. He also noted that for the 75 patients treated with cilta-cel with an MRD-negative CR or better that lasted at least 12 months, the 30-month progression-free survival (PFS) rate was 93.2% and the 30-month overall survival (OS) rate was 97.3%; for the 79 patients treated with cilta-cel who were MRD-positive or had missing or nonevaluable results, the 30-month PFS rate was 46.8% and the 30-month OS rate was 64.6% (95% CI). Popat additionally stated that all prespecified subgroups, such as those based on age, number of prior lines of therapy, tumor burden, and other factors, favored cilta-cel over standard of care for MRD negativity rates (10-5).
“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 MM as early as second line, shows profound long-term remission rates, including PFS and OS benefits,” Jordan Schecter, MD, vice president, disease area leader, multiple myeloma, at Johnson & Johnson Innovative Medicine, added to the statement.2 “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.”
REFERENCES
1. Popat R, Oriol A, Cavo M, et al. Ciltacabtagene autoleucel (cilta-cel) vs standard of care (soc) in patients with lenalidomide (len)-refractory multiple myeloma (MM) after 1–3 lines of therapy: minimal residual disease (MRD) negativity in the phase 3 CARTITUDE-4 trial.Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract 1027
2. 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 11, 2024. https://innovativemedicine.jnj.com/our-innovation/focus-areas/oncology/carvykti-ciltacabtagene-autoleucel-demonstrated-significantly-higher-rates-of-minimal-residual-disease-mrd-negativity-compared-to-standard-therapies-in-the-cartitude-4-study
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