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.
Authors: Modi Karnav , Akhtar Othman Salim , Al-Jumayli Mohammed , Extermann Martine , Booth-Jones Margaret , De Avila Gabe , Parker Nathan , Castaneda Puglianini Omar Alexis , Grajales-Cruz Ariel , Baz Rachid C. , Blue Brandon Jamaal , Shain Kenneth H. , Alsina Melissa , Liu Hien , Nishihori Taiga , Locke Frederick L. , Hansen Doris K. , Freeman Ciara L. 
Published: June 2023

12052

Background: Multiple myeloma is a disease of older adults with a median age at diagnosis of 68 years (y). Patients (pts) receiving chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory MM (RRMM) often experience detrimental effects due to frailty, comorbidity, and cumulative toxicities. In this study, we evaluated the prevalence and impact of frailty, defined by the simplified frailty score, (SFS; Facon et al, Leukemia 2020), and immuno-nutritional status, using Glasgow-prognostic score (GPS; Proctor et al, Br J Cancer 2011) in a real-world cohort of pts receiving CAR-T therapy for RRMM. Methods: We included all pts treated with commercial CAR-T therapy for RRMM between 2021 - 2023 at Moffitt Cancer Center. The SFS and GPS (CRP > 10 mg/dL, 1 point; albumin < 3.5, 1 point) were calculated for all pts at lymphodepletion. Primary endpoints included overall survival (OS) and progression free survival (PFS). Pearson’s chi-squared tests or Fisher’s exact tests were used to compare association between categorical variables. OS and PFS were estimated used using Kaplan-Meier methods; the log-rank test was used to compare OS and PFS, and a cox-proportional model was used for multivariable analysis (MVA). Results: A total of 139 pts were included, with a median follow up of 6.3 months (m; range, 0.2 to 20.3 m). Median age was 66 y (IQR, 58-72 y); 38% were ≥70 y. Pts were treated with either idecabtagene vicleucel (83%) or ciltacabtagene autoleucel (17%). Around 1/3rd of pts had features of high-risk disease [high disease burden, 30%; high-risk cytogenetics (HR-Cyto), 37%; extramedullary disease (EMD), 37%]. Overall, 30% of pts were categorized as frail and 14% were classified as high-risk GPS (score = 2). There were no significant differences in GPS between older (≥70 y) and younger pts ( < 70 y; p= 0.8). Median OS in the cohort was not reached (NR) and median PFS was 11.7 m. Both frailty and high-risk GPS were associated with inferior PFS (frail vs non-frail, HR 2.0, p= 0.03, high GPS vs low/int, HR 1.7 p = 0.009) and OS (frail vs non-frail, HR 3.0, p = 0.006, high GPS vs low/intermediate, HR 2.1 p = < 0.001). The association of GPS with OS remained significant in a MVA, even after adjusting for high-risk disease factors (high disease burden, HR-Cyto and EMD) and frailty. Pts categorized as frail had a lower median PFS of 5.4 m (vs 12.7m non-frail group, p= 0.025), and inferior median OS of 9.7 m (vs NR in non-frail, p= 0.0039). Conclusions: In a real-world setting, frailty affects almost a third of pts with RRMM receiving CAR-T therapy and is associated with inferior PFS and OS. The GPS, a simple immuno-nutritional score, is highly predictive of survival even after adjusting for the presence of high-risk disease. Studies looking at role of pre-habilitation and other modalities to reduce inflammatory burden prior to CAR-T therapy are warranted.