First line therapy in chronic lymphocytic leukemia: a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013

The aim of this study was to investigate long-term outcome following first line therapy in consecutive chronic lymphocytic leukemia patients in a well defined geographic area (Sweden). All patients diagnosed with chronic lymphocytic leukemia (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) first line treated (n=1053) and for those, depth analysis was performed. Endpoints were overall response rate, progression-free survival, overall survival and safety. Median age was 71 years, 53% had Rai stage III-IV and 97% had performance status grade 0-2. FISH was performed in 57% of patients: 15% had del(17p). Chlorambucil +/- prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine +/- rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine +/- rituximab 75%. Median progression free survival and overall survival was 24 and 58 months, respectively; both significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, sex, age and geographical region (overall survival only). Chlorambucil-treated patients had a median progression free survival and overall survival of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil +/- rituximab in 2013. Infections ≥grade III were significantly associated with treatment; chlorambucil 19% vs fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first line treated chronic lymphocytic leukemia patients with a complete follow-up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.