Which Patient Characteristics Impact Treatment Choice in Elderly Patients with Chronic Lymphocytic Leukemia?

Therapy selection in chronic lymphocytic leukemia (CLL) patients is based on the severity of the disease as well as patient characteristics such as age and comorbidity. National Comprehensive Cancer Network guidelines suggest that frail patients or those with significant comorbidity can be treated with oral chlorambucil (CLB) or single agent rituximab (R-mono). While treatment outcomes are mostly available from clinical trial data in younger patients, less is known about the effect of comorbidities on outcomes in elderly CLL patients in the real-world setting.

The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, was utilized in this retrospective cohort analysis of 3366 first primary CLL patients. Patients were diagnosed between January 1, 1998 to December 31, 2007, were >66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received first-line treatment with any oral or infused therapy. CLB is covered by Medicare Part D and data for its use were only available from 2007–2009 in the SEER-Medicare dataset. The NCI comorbidity index, a widely used and validated measure of comorbidity in cancer patients was assessed using claims in the year prior to diagnosis for each patient. Kaplan-Meier curves and Cox proportional hazards regression assessed survival by treatment type. Date of last follow-up was December 2009.

There were 153 CLB, 606 R-mono, 702 R+IV Chemo, and 1905 IV Chemo-only patients. CLB and R-mono patients were older at diagnosis with mean age of 77 compared to R+IV Chemo (73 years) and IV Chemo-only (76 years; p<.0001). 31% of R-mono patients were over the age of 80 at diagnosis (Table 1). CLB patients were more likely to be female and non-white compared to the other treatment groups (Table 1). R-mono patients had a higher comorbidity burden and were diagnosed with more advanced stage disease compared to other treatment groups (Table 1). R-mono patients also had a significantly higher amount of pre-existing anemia (95% vs. 77–88%; p<.0001) and thrombocytopenia (81% vs. 48–72%; p=0.0184) compared to other treatment groups. In the multivariate survival analysis we compared CLB to R-mono during the time period 2007–2009 and R+IV Chemo to IV Chemo-only during the time period 1998–2009. The unadjusted overall survival was higher for R-mono compared to CLB (log rank p=0.0478). The unadjusted overall survival was higher for R+IV Chemo compared to IV Chemo-only (log rank p <.0001) with 5-year overall survival rates of 72% (SE=1.09) versus 52% (SE=1.03) respectively. In multivariate survival analysis, adjusting for age, sex, race, stage, comorbidity, income, diagnosis year and geographic region, IV Chemo-only patients had a 39% higher risk of death compared to R+IV Chemo patients (HR=1.39; 95% CI=1.18-1.62) and CLB patients had a non-significant 2-fold higher risk of death compared to R-mono patients (HR=2.27; 95%CI=0.96-5.38). Increasing age and increasing comorbidity score were significantly associated with higher risks of mortality.

Patient characteristics such as age, comorbidity burden and gender appear to be important factors in prescribing treatment for CLL. R-mono patients were the oldest with more advanced stage disease at diagnosis and highest comorbidity burden while R+IV Chemo patients were the youngest with earlier stage disease and lowest comorbidity burden. R-containing regimens exhibited a greater survival benefit compared to oral or infused chemo-only regimens.

Satram-Hoang:Genentech, Inc.: Consultancy. Reyes:Genentech, Inc.: Employment, Roche Stock Other. Skettino:Genentech, Inc. : Employment, Roche Stock Other.