A validated composite comorbidity index predicts outcomes of CAR T-cell therapy in patients with diffuse large B-cell lymphoma. Blood Adv 2023 Jul 25;7(14):3516-3529
Date
02/04/2023Pubmed ID
36735393Pubmed Central ID
PMC10362276DOI
10.1182/bloodadvances.2022009309Scopus ID
2-s2.0-85158873555 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
Chimeric antigen receptor T-cell therapy (CART) has extended survival of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). However, limited durability of response and prevalent toxicities remain problematic. Identifying patients who are at high risk of disease progression, toxicity, and death would inform treatment decisions. Although the cumulative illness rating scale (CIRS) has been shown to correlate with survival in B-cell malignancies, no prognostic score has been independently validated in CART recipients. We retrospectively identified 577 patients with relapsed/refractory DLBCL indicated for CART at 9 academic centers to form a learning cohort (LC). Random survival forest modeling of overall survival (OS) and progression-free survival (PFS) was performed to determine the most influential CIRS organ systems and severity grades. The presence of a severe comorbidity (CIRS score ≥ 3) in the respiratory, upper gastrointestinal, hepatic, or renal system, herein termed "Severe4," had the greatest impact on post-CART survival. Controlling for other prognostic factors (number of prior therapies, Eastern Cooperative Oncology Group performance status, BCL6 translocation, and molecular subtype), Severe4 was strongly associated with shorter PFS and OS in the LC and in an independent single-center validation cohort (VC). Severe4 was also a significant predictor of grade ≥3 cytokine release syndrome in the LC, while maintaining this trend in the VC. Thus, our results indicate that adverse outcomes for patients with DLBCL meant to receive CART can be predicted using a simplified CIRS-derived comorbidity index.
Author List
Shouse G, Kaempf A, Gordon MJ, Artz A, Yashar D, Sigmund AM, Smilnak G, Bair SM, Mian A, Fitzgerald LA, Bajwa A, Jaglowski S, Bailey N, Shadman M, Patel K, Stephens DM, Kamdar M, Hill BT, Gauthier J, Karmali R, Nastoupil LJ, Kittai AS, Danilov AVAuthor
Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic Combined Chemotherapy ProtocolsComorbidity
Humans
Immunotherapy, Adoptive
Lymphoma, Large B-Cell, Diffuse
Prognosis
Retrospective Studies
