Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials

Abstract

This study investigated the impact of comorbidity in 555 patients with chronic lymphocytic leukemia enrolled in two trials of the German Chronic Lymphocytic Leukemia Study Group on first-line treatment with fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Patients with two or more comorbidities and patients with less than two comorbidities differed in overall survival (71.7 versus 90.2 months; P<0.001) and progression-free survival (21.0 versus 31.5 months; P<0.01). After adjustment for other prognostic factors and treatment, comorbidity maintained its independent prognostic value in a multivariate Cox regression analysis. Chronic lymphocytic leukemia was the major cause of death in patients with two or more comorbidities. Disease control in patients with two or more comorbidities was better with fludarabine plus cyclophosphamide than with fludarabine treatment, but not with fludarabine compared to chlorambucil treatment. These results give insight into interactions between comorbidity and therapy of chronic lymphocytic leukemia and suggest that durable control of the hematologic disease is most critical to improve overall outcome of patients with increased comorbidity. The registration numbers of the trials reported are NCT00276848 and NCT00262795.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.

Overall survival (OS) by number of comorbidities. Kaplan-Meier estimates for (A) all subjects, (B) CLL4 subjects, (C) CLL5 subjects. Hazard ratios (D) of prognostic factors identified by multivariate analysis (boxes represent the hazard ratios, lines the 95% confidence intervals). TK: thymidine kinase; β2M: β2 microglobulin.

Figure 2.

Progression-free survival (PFS) by number of comorbidities. Kaplan-Meier estimates for (A) all subjects, (B) CLL4 subjects, (C) CLL5 subjects. Hazard ratios (D) of predictive factors identified by multivariate analysis (boxes represent the hazard ratios, lines the 95% confidence intervals). FC: fludarabine+cyclophosphamide; TK: thymidine kinase; β2M: β2 microglobulin.

Figure 3.

Hazard ratios (HR) for progression-free survival by number of comorbidities and treatment. (A) Fludarabine+cyclophosphamide (FC) versus fludarabine (F), (B) F versus chlorambucil (CLB).