The Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI): A Three-Factor Comorbidity Model

• Authors: Max J Gordon, Oregon Health & Science University; Andy Kaempf, Knight Cancer Institute; Andrea Sitlinger, Duke Cancer Institute; Geoffrey Shouse, City of Hope Comprehensive Cancer Center; Matthew Mei, City of Hope Comprehensive Cancer Center; Danielle M Brander, Duke Cancer Institute; Tareq Salous, Cleveland Clinic; Brian T Hill, Cleveland Clinic; Hamood Alqahtani, Moores Cancer Center at UC San Diego, San Diego; Michael Choi, Moores Cancer Center at UC San Diego, San Diego; Michael C Churnetski, Emory University; Jonathon Cohen, Emory University; Deborah M Stephens, University of Utah; Tanya Siddiqi, City of Hope Comprehensive Cancer Center; Xavier Rivera, University of Arizona; Daniel Persky, University of Arizona; Paul Wisniewski, Swedish Cancer Center; Krish Patel, Swedish Cancer Center; Mazyar Shadman, Fred Hutchinson Cancer Research Center; Byung Park, Knight Cancer Institute; Alexey V Danilov, Knight Cancer Institute
• Journal Title: CLINICAL CANCER RESEARCH
• Volume: Volume 27, Number 17
• Publisher: AMER ASSOC CANCER RESEARCH | 2021-09-01, Pages 4814-4824
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1078-0432.CCR-20-3993
• Subjects: Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; SURVIVAL; IBRUTINIB; OBINUTUZUMAB; VALIDATION; RITUXIMAB; DISEASE; TREES

Abstract

Purpose: Comorbid medical conditions define a subset of patients with chronic lymphocytic leukemia (CLL) with poor outcomes. However, which comorbidities are most predictive remains understudied. Experimental Design: We conducted a retrospective analysis from 10 academic centers to ascertain the relative importance of comorbidities assessed by the cumulative illness rating scale (CIRS). The influence of specific comorbidities on event-free survival (EFS) was assessed in this derivation dataset using random survival forests to construct a CLL-specific comorbidity index (CLL-CI). Cox models were then fit to this dataset and to a single-center, independent validation dataset. Results: The derivation and validation sets comprised 570 patients (59% receiving Bruton tyrosine kinase inhibitor, BTKi) and 167 patients (50% receiving BTKi), respectively. Of the 14 CIRS organ systems, three had a strong and stable influence on EFS: any vascular, moderate/severe endocrine, moderate/severe upper gastrointestinal comorbidity. These were combined to create the CLLCI score, which was categorized into 3 risk groups. In the derivation dataset, the median EFS values were 58, 33, and 20 months in the low, intermediate, and high-risk groups, correspondingly. Two-year overall survival (OS) rates were 96%, 91%, and 82%. In the validation dataset, median EFS values were 81, 40, and 23 months (twoyear OS rates 97%/92%/88%), correspondingly. Adjusting for prognostic factors, CLL-CI was significantly associated with EFS in patients treated with either chemo-immunotherapy or with BTKi in each of our 2 datasets. Conclusions: The CLL-CI is a simplified, CLL-specific comorbidity index that can be easily applied in clinical practice and correlates with survival in CLL.