The Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI) Predicts Survival and Tolerance of Ibrutinib Therapy in Patients with CLL: A Multicenter Retrospective Cohort Study

Introduction: Medical comorbidities influence survival in CLL. We previously reported on a simplified CLL-specific comorbidity scale, the CLL-CI (Gordon et al. 2019), which required assessment of only three organ systems and was predictive of outcomes in a heterogeneous retrospective patient cohort. Herein we analyzed CLL-CI among patients treated with ibrutinib. Methods: This retrospective study included 339 CLL patients treated with ibrutinib at 9 academic centers between 2014-2019. Vascular, endocrine and upper-gastrointestinal organ systems were assessed at the time of ibrutinib initiation. Each was scored from 0 to 3, in order of increasing severity of dysfunction to generate the CLL-CI score (range, 0-9; Figure A). As established previously, CLL-CI≥2 was deemed high-risk. Event free survival (EFS) was measured from start of ibrutinib to development of new CLL-related symptoms, disease progression, start of a new therapy or death. Overall survival (OS) was measured from treatment initiation to death. Patients with no EFS or OS events were censored at last follow up. The Kaplan-Meier method and log-rank test were used to estimate and compare survival. Multivariable Cox regression was utilized to model EFS and OS. Differences between CLL-CI groups were evaluated with Wilcoxon rank sum and Fisher’s exact tests. Results: Median age was 68 years (range, 30-91), 240 (71%) were treated in the relapsed/refractory setting (range of prior therapies, 0-10). Advanced Rai stage (3-4) was present in 206 (61%) and TP53 aberrancy was present in 93 (27%) patients at the start of ibrutinib therapy. Median follow up was 23 months (range, 1-71). CLL-CI score was high (≥2) in 202/339 patients (60%). Patient characteristics were well balanced between subgroups (CLL-CI