Initial Characteristics, Treatment and Prognosis Of Elderly (≥ 70 years) Patients With Chronic Lymphocytic Leukemia (CLL): An Analysis Of a Series Of 367 Cases
Authors: Baumann Tycho , Delgado Julio , Santacruz Rodrigo , Martínez-Trillos Alejandra , Royo Cristina , Navarro Alba , Pinyol Magdalena , Rozman María , López Cristina , Villamor Neus , Aymerich Marta , Pereira Arturo , Carrió Anna , Montserrat Emili 
Published: October 2019

Abstract

Introduction
Although CLL predominates in the elderly, there are few studies focusing on the characteristics, treatment, and prognosis of elderly patients with CLL.

Patients and Methods
Retrospective single center study of 949 patients diagnosed with CLL between 1990 and 2012. We defined two age-groups:<70 years (“young”, n=582) and ≥ 70 (“elderly”, n=367). Statistical analysis was performed with SPSS and R.

Results
Baseline characteristics of patients are shown in the Table. Median follow-up time was 7.8 years (0.1-23.1) for the overall series. Elderly patients presented with more advanced clinical stage (p<.001) and higher B2M (p<.001) than younger ones. However, elderly patients presented with a lower WBC count (19.6 vs. 23.6 x 109/L; p<.001) and a longer LDT (p=.004). In contrast to younger patients, both sexes were equally distributed within the elderly (p<.001). There were no significant differences regarding ZAP70, FISH cytogenetics, IGHV mutational status and mutations of NOTCH1 and SF3B1. Elderly patients were treated less frequently (39% vs. 62%; p<.001; TTFT 23.8% vs. 41.9% at 3 years; p<.001) and the type of treatment given to elderly vs. younger patients was: alkylating agents (70% vs. 36%), purine analogs (10% vs. 32%), chemoimmunotherapy (5% vs. 25%), other (15% vs. 7%) (p<.001). The response rate was lower in elderly patients (49 % with 14% CR vs. 69% with 31% CR; p<.001). The overall survival (OS) was shorter in the elderly (6.6 vs. 13.3 years; p<.001) in whom a higher CLL-unrelated mortality (34.9% vs. 6.9% at 10 years; p<.001) was observed. The univariate analysis showed a correlation between advanced clinical stage (p<.001), increased B2M (p<.001), 11q- and 17p- (p=.016), high ZAP70 (p<.001), unmutated IGHV (p=.002) and NOTCH1 (p=.002) and SF3B1 mutations (p<.001) and shorter OS. A high co-morbidity index at diagnosis (CIRS-D >6) also correlated with OS (p=.064). With the only exception of cytogenetics by FISH all variables included in the multivariate analysis retained independent prognostic value (clinical stage: HR 1.68, p=.012; ZAP-70: HR 1.64, p=.01; CIRS-D: HR 1.42, p=.035 and B2M: HR 1.09, p=.021). IGHV mutational status, NOTCH1 and SF3B1 mutations were not included in the analysis due to missing data. In elderly patients requiring treatment only co-morbidity burden at treatment initiation (CIRS-T>4: HR 2.13, p=.009) and response to therapy (PR vs. CR: HR 2.03, p=.039; and failure vs. CR: HR 4.33, p<.001) had independent prognostic value for OS.

Conclusions
Patients above 70 years were diagnosed at more advanced phases of the disease than younger ones but no significant differences in the biology of the disease were observed. Importantly, once patients required treatment only co-morbidity and response to therapy were prognostically relevant. Unfortunately, however, only a small proportion of elderly patients could receive effective therapy as currently conceived. In addition, an important fraction of patients died because of causes not related to CLL. These findings underscore the importance of developing active and well tolerated treatments, as well as that of a comprehensive medical care for elderly patients with CLL.

Disclosures:
No relevant conflicts of interest to declare.