A validated composite comorbidity index predicts outcomes of CAR T-cell therapy in patients with diffuse large B-cell lymphoma

Abstract

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 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, molecular subtype), Severe4 was strongly associated with shorter PFS and OS in the LC (hazards ratio [HR]=2.15 and 1.94, respectively; p<0.001) and in an independent single-center validation cohort (VC) (n=218; HR=1.85, p=0.003; HR=1.70, p=0.019, respectively). Severe4 was also a significant predictor of grade ≥3 cytokine release syndrome in the LC (odds ratio [OR]=2.43, p=0.042), while maintaining this trend in the VC (OR=2.05, p=0.114). 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.

Chimeric antigen receptor‐T cell therapy shows similar efficacy and toxicity in patients with diffuse large B‐cell lymphoma aged 70 and older compared to younger patients: A multicenter cohort study

“…At present, several study groups aim at optimizing the assessment of comorbidities with respect to the outcome of CAR‐T cell therapies 26–29 . Despite being associated with reduced PFS as highlighted in the present study and also shown by other analyses, 27,28 functional scores such as ECOG performance score do not capture comorbidities, and good performance scores are usually part of CAR‐T eligibility criteria in several countries 2,28 . Thus, given the already comparable outcomes for elderly patients, effective and easy‐to‐use assessment tools are needed to further optimize patient selection, particularly among older patients to further reduce toxicities.…”

High comorbidity indexes predict 30-day mortality after percutaneous endoscopic gastrostomy

“…Furthermore, morbidities and their corresponding weighted scores listed in CCI were initially assigned and validated for predicting the 10-years mortality (12). CIRS is another comorbidity index that has been validated as a mortality predictor (13), and its e cacy to predict the prognosis of elderly patients with hematopoietic malignancy was recently reported (14,15). The OR in multivariate analysis, AUC values in ROC analysis, and mortality were higher in patients with the highest quartile of CIRS than those with the highest quartile of CCI.…”

Car-T Cell Therapy in Large B Cell Lymphoma

“…[53][54] A recent study used the CIRS to define a prognostic score predictive of outcomes of CAR-T cell therapy in DLBCL patients. 55 Particularly, a CIRS 3 in the respiratory, upper gastrointestinal, hepatic, or renal system, defined as "severe 4", predicted shorter PFS and OS and a CRS of grade 3. 55 Therefore, a simplified CIRS-derived comorbidity index may predict adverse outcomes in DLBCL patients undergoing CAR-T cell therapy.…”