Johnson & Johnson Innovative Medicine's CARVYKTI (ciltacabtagene autoleucel), known generically as cilta-cel, has demonstrated positive results in a subgroup analysis from the Phase III CARTITUDE-4 study, offering new hope for multiple myeloma (MM) patients experiencing early relapse after initial therapy. The findings, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, suggest a significant reduction in the risk of disease progression or death with cilta-cel administration.
Cilta-cel's Impact on Early Relapse Patients
The subgroup analysis focused on patients who experienced an early relapse after initial MM therapy. The data indicated a 73% reduction in the risk of disease progression or death following cilta-cel treatment. This suggests a potential for cilta-cel to become a crucial intervention in earlier lines of therapy for MM patients.
CARTITUDE-4 Study Details
The CARTITUDE-4 trial is designed to evaluate the efficacy and safety of cilta-cel compared to standard treatment regimens, specifically pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd), in adult patients with relapsed and lenalidomide-refractory MM. The trial had already met its primary endpoint of improving progression-free survival in January 2023.
The subgroup analysis included patients who had received one prior line of therapy (LOT), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and were lenalidomide-refractory. After a median follow-up of 16 months, the median progression-free survival (PFS) rate was not reached among patients who received cilta-cel.
Outcomes in Functional High-Risk Multiple Myeloma
An additional subgroup of 79 patients with functional high risk (FHR) multiple myeloma was analyzed. The 40 patients treated with cilta-cel showed more profound responses: 88% overall response rate versus 80%, 68% complete response (CR) or better versus 39%, and 65% minimal residual disease (MRD) negativity versus 10%, compared to those treated with standard therapies. Furthermore, the cilta-cel group experienced a longer median duration of response (mDOR).
Expert Commentary
Luciano Costa, professor of medicine and director of the Multiple Myeloma Program, University of Alabama at Birmingham, and the study’s principal investigator, stated, “This subset analysis of CARTITUDE-4 provides strong evidence that these patients greatly benefit from cilta-cel and will help healthcare professionals better understand the potential of this therapy.”
Jordan Schecter, VP, disease area leader, multiple myeloma at Johnson & Johnson Innovative Medicine, added, “Many patients with FHR multiple myeloma from the CARTITUDE-4 subgroup analysis experienced deep and durable responses following the single infusion of cilta-cel, further supporting the potential to treat a broader patient population.”
Implications for Multiple Myeloma Treatment
The positive data from the CARTITUDE-4 subgroup analysis, particularly in early relapse and functional high-risk patients, underscores the potential of cilta-cel to improve outcomes in a broader range of multiple myeloma patients. These findings may influence treatment strategies and expand the use of cilta-cel in the future. The recent vote by the FDA's Oncologic Drugs Advisory Committee (ODAC) supporting minimal residual disease as a surrogate endpoint for accelerated approvals of new MM therapies further emphasizes the importance of these results.
