Skip to Main Content

Advertisement intended for health care professionals

Skip Nav Destination

MRD Status Important Prognostic Factor for R/R MM Treated With T-Cell Redirecting Therapies

January 30, 2025

February 2025

Leah Lawrence

Leah Lawrence is a freelance health writer and editor based in Delaware.

Measurable residual disease (MRD)-negative complete response (CR) was the most relevant prognostic factor identified among patients with relapsed or refractory multiple myeloma (R/R MM) treated with T-cell redirecting immunotherapy, according to the results of a study published in the American Journal of Hematology.

“Undetectable MRD is frequently considered a treatment endpoint, and there is increasing interest in using it for treatment decisions in MM,” said Bruno Paiva, PharmD, PhD, of Clínica Universidad de Navarra in Pamplona, Spain. “That is because of the plethora of data collected in the past 20 years in multiple treatment scenarios that have consistently shown that MRD is one of the most relevant prognostic factors.”

Until recently, Dr. Paiva said, there has still been uncertainty about the role of MRD as a marker of treatment efficacy in the context of more recently approved T-cell redirecting therapies like chimeric antigen receptor (CAR) T-cell therapies and T-cell engagers (TCE). This question is especially relevant in the context of the recent recommendation from the U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) that MRD could serve as an endpoint for accelerated approval in MM trials. In fact, the data presented at the ODAC hearing lacked clinical trials investigating T-cell redirecting therapies, Dr. Paiva said.

Dr. Paiva and colleagues analyzed MRD using next-generation flow cytometry in 201 patients with R/R MM treated in clinical trials of CAR T-cell therapies (98 patients) and TCEs (103 patients); MRD status was available for 147 of the 201 patients.

Patients who achieved MRD-negative status had an 89% reduction in the risk of progression or death. Median progression-free survival (PFS) for those with MRD-negative status was 20 months compared with three months for MRD-positive status (hazard ratio [HR] = 0.11; 95% CI 0.07-0.16; p<0.001). The median overall survival was not reached in the MRD-negative population compared with seven months in the MRD-positive population (HR=0.15; 95% CI 0.09-0.24; p<0.001).

“In contrast to other treatment scenarios, in this population, attaching MRD negativity to a CR was important to identifying patients achieving the longest survival,” Dr. Paiva said. This may be associated with the higher probability of extramedullary disease (EMD) in those with R/R MM.

Of the included patients, 28%, 20%, and 52% had one, two, and three or more MRD assessments, respectively. Sustained MRD-negative status occurred in 60 patients. Patients with sustained MRD negativity had improved survival outcomes compared with those who did not.

Median PFS for patients with sustained MRD negativity was 37 months compared with 12 months in patients with transient MRD negativity and three months in the MRD-positive patients.

Additionally, although there was a higher rate of MRD negativity in patients treated with CAR T-cell therapy compared with TCE, Dr. Paiva said there were no differences in the survival outcomes of patients who were MRD negative or MRD positive when stratified according to the type of T-cell redirecting immunotherapy.

“This showed that reaching the MRD-negative finish line is more important than the road leading to it, which emphasizes the role of MRD as a treatment endpoint and as a biomarker for accelerated approval of new drugs based on MRD-negative rates in MM clinical trials,” Dr. Paiva said.

Multivariable analysis showed that only CR and MRD status were independent prognostic factors for survival; the number of prior lines of treatment, International Staging System, cytogenetic risk, EMD, and type of T-cell redirecting immunotherapy were not prognostic.

“These findings define MRD as a very important feature to assess in patients achieving CR,” Dr. Paiva said. “New studies must be performed to answer the question, ‘What do we do next if a patient is MRD positive or negative?’”

Dr. Paiva said the study was limited by its retrospective nature, which affected how many patients had MRD data available.

“If we included only patients who were tested, there would be a bias in the population,” Dr. Paiva said. “Therefore, we included all patients treated with these T-cell redirecting therapies that became approved for the treatment of R/R MM, and patients who did not have MRD assessment because of early disease progression or because they did not achieve CR were inputted as MRD positive.”

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Zabaleta A, Puig N, Cedena M-T, et al. Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T-cell redirecting immunotherapy [published online ahead of print, 2024 Nov. 16]. Am J Hematol. doi: 10.1002/ajh.27526.

Advertisement intended for health care professionals

Connect with us:

CURRENT ISSUE
February 2025

Advertisement intended for health care professionals

Close Modal

or Create an Account

Close Modal
Close Modal

Advertisement intended for health care professionals