Survival Improvement of Patients with Chronic Lymphocytic Leukemia (CLL) in Routine Care 1995 - 2017

Introduction: Treatment options, progression free survival (PFS) and overall survival (OS) for patients with CLL have improved during the last 20 years in randomized controlled trials (RCT). Due to necessary inclusion- and exclusion criteria results from RCT are difficult to translate into routine care. We asked the question whether improved treatment options found in RCT are applied in routine care and whether they lead to a prolongation of survival.

Methods: All patients with CLL treated in a hematology-oncology group practice in Germany between 1995-2017 were documented retrospectively concerning diagnosis, treatment and survival in a database and analyzed statistically using SPSS.

Results: 724 outpatients with a median age of 67 (35-92) were analyzed. 427 (59%) were male, 297 (41%) were female. At diagnosis 556 (77%) were in Binet stage A, 91 (13%) stage B, 36 (5%) stage C and for 41 patients (6%) the stage couldn't be retrieved, mostly due to external diagnosis. The Charlson age adjusted comorbidity index (aaCCI) was distributed as follows: aaCCI ≤ 3 (19%), aaCCI 4 (27%), aaCCI 5 (24%) and aaCCI > 5 (31%). 56% received treatment during the evaluation period. Treatment consisted of bendamustine containing protocols in 69%, rituximab containing protocols in 66%, chlorambucil containing protocols in 53% and fludarabine containing protocols in 39%. 4% received obinutuzumab containing regimens, 9% ibrutinib and 3% idelalisib + rituximab. 10 patients (3%) had an allogeneic transplantation. Patients received a median of 2 lines of therapy (1-13). OS according to Binet stage was A 13.9 years (0.1-37.4), B 9.2 years (1.4-29.3) and C 7.9 years (0.5-19.4) respectively. OS was strongly correlated to the aaCCI: aaCCI 2-3 23.7 years (2.3-37.4), aaCCI 4 14.2 years (0.7-29.3), aaCCI 5 9.7 years (0.1-19.5) and aaCCI > 5 7.2 years (0.1-18.9). Median OS from the start of therapy improved over time: 1995-2001: 5.8 years (1.3-23.4), 2002-2008: 6.1 years (0.1-16.0+) and 2009-2017 median not reached (0.1-9.2+).

Conclusions: Survival of patients with CLL has improved in routine care during the last 20 years most likely due to improved treatment options. Survival was strongly related to disease stage, comorbidities and whether therapy included an anti-CD20-monoclonal antibody.