Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States

Abstract

Background: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is > 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting.

Methods: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model.

Results: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p < 0.0001) and chemotherapy-alone regimens (p < 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment < 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006).

Conclusion: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients.

Trial registration: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010.

Keywords: Chemoimmunotherapy; Chronic lymphocytic leukemia; Connect® CLL registry; Elderly; Prognostic.

Fig. 1

Cause of death among patients enrolled on the registry. Cause of death is shown for a patients aged < 75 years in LOT1; b patients aged ≥ 75 years in LOT1; c patients aged < 75 years in LOT ≥ 2; d patients aged ≥ 75 years in LOT ≥ 2. Rounding of values may cause totals to be equal, >, or < 100%. CLL chronic lymphocytic leukemia, LOT1 first line of therapy, LOT ≥ 2 second line of therapy or greater

Fig. 2

Overall survival in elderly CLL patients vs. younger patients. Kaplan–Meier curves of OS for patients in a LOT1 and b LOT ≥ 2 stratified by age. Percentages are rounded to the nearest whole number. CI confidence interval, LOT1 first line of therapy, LOT ≥ 2 second line of therapy or greater, OS overall survival

Fig. 3

Cumulative incidence of deaths in elderly CLL patients vs. younger patients. CIF of CLL-related deaths stratified by age in a LOT1 and b LOT ≥ 2, and CLL- or infection-related deaths stratified by age in c LOT1 and d LOT ≥ 2, demonstrating increased mortality in elderly CLL patients (red line). Horizontal dashed line shows median survival in patients ≥ 75 years. CI confidence interval, CIF cumulative incidence functions, CLL chronic lymphocytic leukemia, LOT1 first line of therapy, LOT ≥ 2 second line of therapy or greater