Background: Chronic Lymphocytic Leukemia (CLL) is the most prevalent adult leukemia in western countries and disparities in outcomes based on race have been identified. In national registry data and institutional studies, black patients were found to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. However, racial disparities commonly correlate with access to care, comorbidities, and differences in treatment. In order to limit these potential confounders not available in other data, we studied patients in the Veterans Health Administration (VHA) network to understand differences in treatment and outcomes of black vs. non-black patients with CLL in a single care delivery system.
Methods: We used the Veterans Administration Central Cancer Registry to identify patients diagnosed with CLL between September 1999 and October 2015 who were identified by race. Pharmacy records were used identify patients who received fludarabine, cyclophosphamide, rituximab, bendamustine, or chlorambucil as initial treatment of CLL. Comparisons between groups were performed with t-test or chi-square as appropriate. Comorbidity was assessed with Charlson (Romano) index and median survival by the Kaplan-Meier method. Cox proportional hazards regression modeling was used to assess associations between race and while adjusting for age, comorbidity, type of treatment, time to treatment and BMI. The study was approved the Saint Louis VA Medical Center institutional review board.
Results: An initial cohort of 7155 patients with CLL was identified, of whom 2597 received chemotherapy within the VHA. Of those receiving chemotherapy, 14.8% were black (345/2597). The median year of treatment was 2006. Black patients were younger (64.0 years vs. 67.1, p<0.001) with similar mean comorbidity scores (2.3 vs. 2.2 p=0.24) compared to non-black patients. The mean time from CLL diagnosis to treatment was shorter for black patients (24.2 months vs. 28.3 p=0.02). Black patients were more likely to receive fludarabine based regimens (43.6% vs. 30.2%, p<0.001) and less likely to receive chlorambucil (25.5% vs. 32.5%, p=0.01). There were no differences based on race in treatment with bendamustine (10.4% vs. 11.4%, p=0.57), cyclophosphamide (8.6% vs. 11.0%, p=0.15) or rituximab alone (11.9% vs 14.9%, p=0.13). Second line treatment was administered to 197 black patients, which was more frequent than non-black (51.2% vs. 43.9%, p=0.01). Mean overall survival from diagnosis was 68.2 months in black patients compared to 72.5 months in non-black (p=0.07) and median overall survival was 76 vs. 83 months (p=0.051) respectively. Mean survival from start of chemotherapy (43.7 months vs. 43.6, p=0.95) in black and non-black patients and median survival was 47 vs. 50 months (p=0.34) respectively. In unadjusted analyses, black race was not associated with differences in survival after chemotherapy (hazard ratio (HR) 1.07, 95% CI:0.93-1.22, p=0.34) nor in overall survival (1.14, 95% CI:0.99-1.30, p=0.051). After adjusting for age, comorbidity index, BMI, duration of observation and treatment characteristics, black race was associated with poorer overall survival (adjusted HR 1.25, 95% CI:1.08-1.44, p=0.002) and survival after chemotherapy (adjusted HR 1.22, 95% CI:1.05-1.41, p=0.008).
Conclusions: In this retrospective analysis of patients treated for CLL at the VHA, black patients had worse survival compared to non-black patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine. Future studies should be performed to understand potential differences in CLL disease biology in different racial groups as a potential cause of adverse outcomes in this patient population.
Carson:Washington University in St. Louis: Employment; Roche: Consultancy; Flatiron Health: Employment. Sanfilippo:BMS/Pfizer: Speakers Bureau.
Asterisk with author names denotes non-ASH members.
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