Although chimeric antigen receptor (CAR) T-cell therapies have transformed the care of relapsed or refractory multiple myeloma (R/R MM), older adults have been underrepresented in the pivotal trials that have led to their approval. Now, results from the largest reported dataset of older adults indicate that older adults and frail patients with R/R MM who were treated with the anti-B-cell maturation agent (BCMA) CAR-T product idecabtagene vicleucel (ide-cel) had comparable efficacy to younger and non-frail patients. Othman Akhtar, MD, of the Medical College of Wisconsin in Milwaukee, and colleagues published the findings in Blood Advances.1
These results fill a critical knowledge gap in the outcomes of older and frail patients with R/R MM receiving anti-BCMA CAR-T therapy.2 The group previously reported that, in a real-world setting, frailty affects approximately one-third of patients with R/R MM who receive CAR-T therapy. Frailty is associated with inferior progression-free survival (PFS) and overall survival (OS) in MM.2 They found that the Glasgow Prognostic Score, a simple immuno-nutritional score, is highly predictive of survival even after adjusting for high-risk disease.
The current retrospective study used data from the Center for International Blood and Marrow Transplantation on U.S. patients who received ide-cel between May 2021 and June 2023 and had at least 100 days of follow-up. The study was limited because data on prior therapy, including bridging strategies, were incomplete for some patients. Of the 821 patients, 30.6% were 70 years of age or older. Cytokine release syndrome (CRS) rates were similar across age groups, and there were no differences in the rate of response at six months by age group. The researchers noted decreased relapse and improved survival in the older adult subgroup. While researchers did observe higher rates of immune-effector cell-associated neurotoxicity syndrome (ICANS), they saw no increase in treatment-related mortality (TRM) and no differences in the higher grades of infections.
The investigators were able to determine a frailty score in 93.3% of the patients, and they subsequently identified 44.8% of patients as frail. They observed no differences in response (overall or complete response), PFS, or OS at six months between frail patients and non-frail patients.
“I would have thought that maybe frailty had an effect on outcomes of patients,” said author Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center in New York, expressing surprise that this was not the case. “Don’t hold back on this treatment for patients who otherwise would qualify but they have frailty.”
Dr. Usmani explained that older adults are heterogeneous in frailty and comorbidity burden. Therefore, he and his colleagues recommend using validated frailty assessment tools such as the simplified frailty index (SFI). “You can be young and have comorbidities that make you frail,” he said. “Frailty encompasses somebody’s ability to function in day-to-day activities and take care of themselves.” The SFI thus determines frailty based on a combination of daily life and physical function components, and the provider determines the assessment after seeing the patient. He explained that ide-cel is offered on a case-by-case basis after a frailty assessment. He anticipated that these new findings will result in practitioners, in his center and other centers, making ide-cel available to more patients who are older and frail.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Akhtar O, Oloyede T, Brazauskas R, et al. Outcomes of older adults and frail patients receiving idecabtagene vicleucel: a CIBMTR study [published online ahead of print, 2024 Dec. 30]. Blood Adv. doi: 10.1182/bloodadvances.2024014970.
- Modi K, Akhtar OS, Al-Jumayli M, et al. Association of frailty and high-risk immuno-nutritional score with outcomes in patients with relapsed and refractory multiple myeloma treated with chimeric antigen receptor T-cells. J Clin Oncol. 2023;41(16):12052-12052.
