Dr Krishnan on the Role of Cilta-Cel in High-Risk Multiple Myeloma

Amrita Krishnan, MD, executive medical director, Hematology, City of Hope Orange County; director, the Judy and Bernard Briskin Multiple Myeloma Center; professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the potential role for CAR T-cell therapies, such as ciltacabtagene autoleucel (Carvykti; cilta-cel), in the early-relapsed setting for patients with high-risk multiple myeloma.

The phase 3 CARTITUDE-4 trial (NCT04181827) compared the BCMA-directed CAR T-cell therapy, cilta-cel with standard-of-care (SOC) regimens in a population of functionally high-risk patients with relapsed/refractory multiple myeloma. Findings from this trial supported the April 2024 FDA approval of cilta-cel for adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide (Revlimid).

At the 2024 ASCO Annual Meeting, long-term follow-up data from the high-risk population in CARTITUDE-4 highlighted the potential of cilta-cel in the early relapsed setting, Krishnan begins. The results showed a significant improvement in median progression-free survival (PFS) and overall response rate (ORR) with cilta-cel vs SOC regimens, she reports. Within the high-risk subset, the median PFS with cilta-cel was comparable with that of standard-risk patients, suggesting that cilta-cel could mitigate the impact of high-risk features in early relapse.

However, the decision to use cilta-cel in the early-relapsed setting remains highly individualized, and involves balancing the risks and benefits for each patient, Krishnan states. Cilta-cel may be the preferred approach for some patients who have been CD38-exposed, but not refractory. There are also other groups of patients for whom that may not be the case, she cautions. The choice between cilta-cel and other therapies accordingly depends on several factors, including disease characteristics, patient comorbidities, and shared decision-making between the patient and healthcare provider, Krishnan emphasizes. Although relatively low, the risk of developing neurologic toxicities or secondary malignancies are critical considerations in the shared decision-making process, she adds. Thus, while cilta-cel has demonstrated substantial benefits in a specific patient subset, its role in the in the early relapsed setting continues to evolve based on emerging data and clinical experience, Krishnan concludes.