Presenting Author: James A. Davis, PharmD, BCOP, MUSC College of Pharmacy, Medical University of South Carolina, Charleston, SC
Co-Authors: Danai Dima, MD, Department of Hematology-Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, OH; Nausheen Ahmed, MD, Shaun DeJarnette, and Joseph McGuirk, MD, Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS; Xuefei Jia, MS, Department of Biostatistics and Quantitative Science, Cleveland Clinic, Cleveland, OH; Shahzad Raza, MD, Jack Khouri, MD, Jason Valent, MD, and Faiz Anwer, MD, Department of Hematology-Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, OH; Al-Ola Abdallah, MD, Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS; Hamza Hashmi, MD, Department of Hematology-Oncology, Medical University of South Carolina, Charleston, SC
BACKGROUND: With a median age at diagnosis of 69 years, multiple myeloma (MM) primarily affects elderly patients, of whom many have been excluded from clinical trials evaluating CAR T-cell therapy. It has been shown that chronologic age alone should not be a barrier towards effective treatments including stem cell transplant and CAR T cells, and that instead of age, frailty scores should be incorporated into screening assessments.
OBJECTIVE: Because there is limited literature on the safety and efficacy of CAR T-cell therapy in frail patients, we retrospectively evaluated the clinical characteristics and outcomes of frail patients with MM who received CAR T-cell therapy.
METHODS: Three academic medical centers contributed data that included patients who had received BCMA-directed CAR T-cell therapy. Frailty was defined using the simplified frailty index (score based on age + ECOG performance status + comorbidity index; frail = score ≥2). The outcomes included the incidence and severity of cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), infections, treatment-related mortality, overall response rates (ORRs), progression-free survival (PFS), and overall survival (OS).
RESULTS: Of the 136 patients analyzed (age, 41-81 years), 83 (61%) were considered frail at the time of CAR T cell infusion. The frail group had a significantly higher proportion of renal insufficiency (18% vs 6%), performance status ≥2 (18% vs 2%), triple-class refractoriness, and worse comorbidity burden than the nonfrail group. Although the frail group had less CRS (76% vs 79%) and more ICANS (39% vs 17%) than the nonfrail group, the incidences of grade ≥3 CRS and ICANS were similar. The rates of infection were similar between the groups, with nearly one third of the patients having an infection within 6 months of receiving CAR T cell infusion. With a median follow-up of 7 months, the best ORR was 81% in the frail group versus 96% in the nonfrail group. The median PFS was 6.9 months in the frail group versus 11.1 months in nonfrail group (P=.028). The median OS was 14 months in the frail group and was not reached in the nonfrail group (P=.025). Treatment-related mortality was observed in 7 (8%) patients in the frail group and in 1 patient in the nonfrail group.
CONCLUSION: Most patients in this real-world study were frail by simplified frailty index. Although frail patients had worse performance status and higher comorbidity burden at the time of infusion, the incidence of high-grade toxicities was similar. When compared with the nonfrail group, frail patients had statistically inferior survival outcomes. This study highlights the need for fitness-based assessments to personalize care for patients with MM.
- Rajeeve S, Usmani SZ. How old is too old for CAR-T cell therapies in multiple myeloma? Transplant Cell Ther. 2023;29:343-344.
- Reyes KR, Huang CY, Lo M, et al. Safety and efficacy of BMCA CAR-T cell therapy in older patients with multiple myeloma. Transplant Cell Ther. 2023;29:350-355.
- Facon T, Dimopoulos MA, Meuleman N, et al. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia. 2020;34:224-233.