Editor’s Note: In this captivating interview, Dr. Niels Van de Donk offers an extensive exploration of the recent advancements and future prospects in Chimeric Antigen Receptor T-cell (CAR-T) therapy for relapsed/refractory multiple myeloma (RRMM). Dr. Donk’s insights, ranging from the dynamic landscape of CAR-T targets to pivotal studies like MAJESTEC-1, provide a comprehensive overview of the current status, challenges, and promising directions in the ever-evolving field of RRMM treatment.01 Oncology Frontier: Unpacking the Current Progress in CAR-T Targets for RRMM
Oncology Frontier: Dr. Donk, as a leading figure in the field, could you give us an overview of the current progress in CAR-T targets for relapsed/refractory multiple myeloma (RRMM)?
Dr. Donk: Certainly. CAR-T cell therapies have been targeting B-cell maturation antigen (BCMA) prominently. Notably, Cilta cel has emerged as a standout player, with extended follow-up data showcasing a robust median progression-free survival (PFS) of three years in heavily pretreated RRMM patients, positioning it as the most effective agent in the realm of triple-class refractory disease. Concurrently, ID cell, while effective, exhibits a slightly shorter median PFS of around eleven months. A noteworthy study presented at both EHA and ASCO compared Cilta cel with standard care in earlier lines of treatment (one to three prior lines), uncovering a substantial advantage of Cilta cel over standard treatments. This finding suggests a potential paradigm shift in the treatment approach for RRMM.
02 Oncology Frontier: Decoding the Impact of Teclistamab in RRMM Treatment
Oncology Frontier: Your team recently reported on the TECLISTAMAB (TEC) study targeting BCMA and CD3 in RRMM patients. Could you delve into the details of this study and its implications?
Dr. Donk: Absolutely. The MAJESTEC-1 study has been a pivotal exploration in which we treated 165 patients with Teclistamab as a monotherapy at the recommended phase two dose. With a follow-up nearing two years, the study revealed an impressive overall response rate of 63% in heavily pretreated myeloma patients. These patients had a median of five lines of therapy, and three-quarters were triple class refractory. The depth of response was equally remarkable, with 45% achieving complete remission. Translating these responses into clinical outcomes, we observed a median progression-free survival of eleven months and a median response duration of 22 months, extending to 27 months for those achieving complete remission. Importantly, we effectively managed side effects such as cytokine release syndrome and infections, underscoring the progress made in mitigating these challenges.
03 Oncology Frontier: Peering into the Future of CAR-T Research for RRMM
Oncology Frontier: Looking ahead, what do you envision as the future research directions in CAR-T treatment for RRMM, and what initiatives is your team undertaking?
Dr. Donk: With the proven efficacy of CAR-T cell therapy in advanced stages of RRMM, we are now extending our exploration to earlier lines of therapy. A forthcoming study will compare Cilta cel with transplant in CARTITUDE six, and CARTITUDE Five is set to evaluate Cilta cel in transplant ineligible patients. Beyond BCMA, our future endeavors involve investigating different targets, with the potential incorporation of dual targeting to prevent antigen escape and enhance both progression-free survival and response duration. Additionally, we are keen on delving into strategies aimed at preventing T cell exhaustion. Agents like Lenalidomide, which can improve T cell function, hold promise in this regard.
In conclusion, Dr. Niels Van de Donk provides a panoramic view of the current landscape and the promising trajectory of CAR-T therapy in the intricate realm of RRMM treatment.
TAG: EHA 2023, Interview, Hematological Malignancy, Multiple Myeloma, CAR-T Therapy
