Characteristics, Treatment, and Outcomes of >= 80 Year Old Patients with Chronic Lymphocytic Leukemia (CLL) Enrolled to Prospective Trials of the German CLL Study Group

Introduction: Clinical management of ≥80 year old patients (pts) with CLL remains a challenge due to the very limited amount of data currently available for this age segment. Two retrospective studies reported observational data on characteristics, treatment, and outcomes of ≥80 year old pts not enrolled in a clinical trial (Bairey et al., Meunier et al.). Comparably little is known about ≥80 year old pts who were treated for CLL within clinical trials, however. Methods: Trial populations of seven clinical trials of the GCLLSG (CLL1, CLL5, CLL7, CLL8, CLL9, CLL10, CLL11; total N = 3552) were reviewed and screened for pts ≥ 80 years at frontline treatment. Clinical, laboratory, and genetic data of the identified pts were pooled. Time-to-event data were analysed by Kaplan-Meier methodology. Independent prognostic factors for survival were identified by multivariate analysis using Cox regression modelling with stepwise selection procedures. Results: Among 3552 reviewed GCLLSG trial participants, 152 were aged ≥80 years at initiation of frontline treatment. Pts were identified from CLL11 (n = 132), CLL1 (n = 3), CLL5 (n = 1), CLL7 (n = 3), CLL8 (n = 2), CLL9 (n = 9), and CLL10 (n = 2). Median age was 82 years (range 80-90). Concomitant diseases were present in 99% of the pts and median cumulative illness rating scale (CIRS) score was 8 (0-18). Median creatinine clearance was 46 mL/min (range 17-99 mL/min). Distribution of CLL-IPI risk groups was as follows: 6% low, 19% intermediate, 61% high, and 14% very high. Most pts had Binet stage B (36%) or C (43%). Chemoimmunotherapy with chlorambucil plus obinutuzumab (CLB-OB) or chlorambucil plus rituximab (CLB-R) was administered to 61 (40%) and 56 (37%) pts, respectively. Remaining pts received chlorambucil alone (CLB, n = 19), fludarabine (F, n = 10), F/cyclophosphamide (FC, n = 1), FC/rituximab (FCR, n = 2), or bendamustine/rituximab (BR, n = 3). Rates of grade 3 or 4 neutropenia and infections were 35% and 13%, respectively. Premature treatment discontinuations occurred in 15% of cases and were mostly due to adverse events. The total overall response rate was 92% with 13% complete remissions. Median observation time for all pts was 40.7 months. Median progression-free survival (PFS) and treatment-free survival (TFS) were 17.2 and 32.3 months. A total of 47 pts (31%) received at least one further line of treatment. Median overall survival (OS) was 48.3 months, with adverse events (22%) and progressive CLL (15.8%) being the most frequent causes of death. Standardized mortality ratio was calculated and showed a 1.99 (CI 1.54-2.53) increased risk of death as compared to an age- and sex-matched general population. Independent prognostic factors for OS were 17p deletion and elevated serum thymidine kinase. Conclusion: Findings suggest that antileukemic therapy (incl. Chemoimmunotherapy) is feasible and efficacious in ≥80 year old pts with CLL. However, such pts are still highly underrepresented in clinical trials and even with modern treatment live shorter than age-matched controls of the general population. Keywords: chronic lymphocytic leukemia (CLL); elderly.