Prognostic Impacts of Comorbidities Assessed Through Novel CAR-T‒Specific Comorbidity Index

Despite promising responses with standard-of-care chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), outcomes can vary depending on the condition of patients prior to T-cell infusion. Preexisting comorbidities as scored by the hematopoietic cell transplantation–specific comorbidity index have been shown to be associated with morbidities and mortality following stem-cell transplantation; however, the impact of comorbidities on outcomes with CAR-T therapy is not well established. In response, investigators developed and validated a CAR-T‒specific comorbidity index (CT-CI), and then examined its prognostic value in predicting survival and toxicity outcomes, as presented at the 64th American Society of Hematology 2022 Annual Meeting and Exposition.

Utilizing the cellular therapy registry from the Center for International Blood and Marrow Transplant Research, adult patients with R/R LBCL receiving commercially available CAR-T therapy since FDA approval (axicabtagene ciloleucel, 2017; tisagenlecleucel, 2018) until December 2020 were identified. Patients were randomly assigned to training (50%) and validation (50%) cohorts. Cox proportional hazard model was used to examine risk factors associated with overall survival (OS). A stepwise selection method was used to identify the significant covariates affecting OS, with a significance level of .01. Pairwise interactions between significant factors were tested. A multivariate analysis adjusting for the significant covariates was used to develop a weighted score for each comorbidity based on the magnitude of hazard ratios for OS. The CT-CI score (the sum of weighted scores of individual comorbidities) was then tested in the validation cohort.

Of 1916 patients included, median age was 63.6 years (range, 18.5-91), with 24.7% (n = 473) ≥70 years, and 36.1% were women. Double/triple-hit LBCL and transformed lymphoma was the diagnosis in 13.8% and 24.1% of patients, respectively. Incidences of all-grade cytokine release syndrome (CRS) and immune effector call–associated neurotoxicity syndrome (ICANS) were 75.4% (grade ≥3 CRS, 8.5%) and 44.4% (grade ≥3 ICANS, 19.5%), respectively. Rates of 12-month (mo) progression-free survival and OS were 42.2% (95% confidence interval [CI], 39.9-44.5) and 61.6% (95% CI, 59.4-63.9), respectively. The primary cause of death was disease progression (73.2%), and incidence of treatment-related mortality was 4.3% (95% CI, 3.4-5.3). At least 1 comorbidity was recorded for 1321 (68.9%) patients, while 558 (29.1%) had none; in 37 patients (1.9%), no reported data were available. Most commonly reported comorbidities were history of cardiac disease (11.8%), diabetes requiring pharmacological treatment in the last 4 weeks (13.8%), psychiatric disturbance requiring intervention in the last 4 weeks (18.1%), and pulmonary disease at the time of T-cell infusion (moderate, 15.0%; severe, 12.2%). History of hepatic impairment or cerebrovascular disease at any prior time, infection requiring antimicrobial treatment continuing after day 0, and diabetes requiring treatment in the last 4 weeks; body mass index <20; moderate-to-severe renal impairment; and severe pulmonary impairment at the time of infusion were associated with significant impacts on OS. Other clinical factors associated with worse OS were lower Karnofsky performance score and history of disease refractoriness. Higher CT-CI scores were associated with worse 1-year OS in the training and validation cohorts (0 vs 1 vs 2 vs ≥3). The CT-CI was not able to predict incidence or severity of CRS or ICANS.

In conclusion, development of a novel CT-CI has shown that comorbidities were predictive of mortality after CAR-T therapy and may influence clinical decisions for treatment selection in high-risk patients with LBCL based on real-world data analysis.

Source

Greenbaum U, Hashmi H, Elsawy M, et al. Prognostic impact of comorbidities on outcomes of patients with relapsed or refractory large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Poster presentation 2025.