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The Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI): A Three-Factor Comorbidity Model
Max J Gordon1, Andy Kaempf2, Andrea Sitlinger3
1Oregon Health and Science University, Portland, Oregon.
Insights
A new chronic lymphocytic leukemia comorbidity index (CLL-CI) identifies vascular, endocrine, and gastrointestinal issues as key predictors of survival. This simplified score aids in clinical practice for predicting outcomes in CLL patients.
Area of Science:
- Hematology
- Oncology
- Clinical Medicine
Background:
- Comorbidities significantly impact outcomes in chronic lymphocytic leukemia (CLL).
- Identifying the most predictive comorbidities for CLL patients remains an area needing further research.
- Existing comorbidity assessments may not be specific enough for CLL prognosis.
Purpose of the Study:
- To determine the relative importance of comorbidities in predicting outcomes for chronic lymphocytic leukemia (CLL) patients.
- To develop and validate a CLL-specific comorbidity index (CLL-CI) using the Cumulative Illness Rating Scale (CIRS).
- To assess the association of the CLL-CI with event-free survival (EFS) and overall survival (OS) in CLL.
Main Methods:
- Retrospective analysis of 570 patients from 10 academic centers (derivation set) and 167 patients (validation set).
- Utilized random survival forests to identify key comorbidities influencing EFS.
- Developed the CLL-CI score based on vascular, endocrine, and upper gastrointestinal comorbidities and validated using Cox models.
Main Results:
- Vascular, moderate/severe endocrine, and moderate/severe upper gastrointestinal comorbidities were strongly associated with EFS.
- The CLL-CI categorized patients into low, intermediate, and high-risk groups, showing distinct median EFS and two-year OS rates in both datasets.
- The CLL-CI demonstrated significant association with EFS in CLL patients treated with chemo-immunotherapy or Bruton tyrosine kinase inhibitors (BTKi).
Conclusions:
- The CLL-CI is a simplified, CLL-specific comorbidity index.
- The CLL-CI can be readily applied in clinical practice.
- The CLL-CI correlates with survival outcomes in patients with chronic lymphocytic leukemia.
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 CLL-CI 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 (two-year 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.
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