TY - JOUR
T1 - The chronic lymphocytic leukemia comorbidity index (CLL-CI)
T2 - A three-factor comorbidity model
AU - Gordon, Max J.
AU - Kaempf, Andy
AU - Sitlinger, Andrea
AU - Shouse, Geoffrey
AU - Mei, Matthew
AU - Brander, Danielle M.
AU - Salous, Tareq
AU - Hill, Brian T.
AU - Alqahtani, Hamood
AU - Choi, Michael
AU - Churnetski, Michael C.
AU - Cohen, Jonathon B.
AU - Stephens, Deborah M.
AU - Siddiqi, Tanya
AU - Rivera, Xavier
AU - Persky, Daniel
AU - Wisniewski, Paul
AU - Patel, Krish
AU - Shadman, Mazyar
AU - Park, Byung
AU - Danilov, Alexey V.
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-20-3993
DO - 10.1158/1078-0432.CCR-20-3993
M3 - Article
C2 - 34168050
AN - SCOPUS:85114187912
SN - 1078-0432
VL - 27
SP - 4814
EP - 4824
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -