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

Abstract

The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007–2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0–2. Fluorescence in situ hybridization (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 PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS 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% versus 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 CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.

Survival improvement of patients with chronic lymphocytic leukemia (CLL) in routine care 1995–2017

“…This is in accordance with data from the German CLL Study Group and other groups showing that treatment with an anti-CD20 antibody is associated with a better overall survival [28][29][30]. Recently a nation-wide real-world study from Sweden reported no survival improvement between 2007-2013 looking at 1053 patients receiving first-line therapy [36]. First-line therapy consisted of chlorambucil in 39% of patients without an anti-CD20-antibody in 95%.…”

“…Our routine care patient cohort had a median age at diagnosis of 67 , which is comparable to data from Spain [34], and a median age at first treatment of 70 . Median age at start of first-line therapy was 71 (31-96) in a Swedish registry [36] and 68 in an American cohort study [37]. The age of our patient population, therefore, seems to be in a range comparable to other real-world data analyzes.…”

“…First-line therapy consisted of chlorambucil in 39% of patients without an anti-CD20-antibody in 95%. Less than 50% of the patients received an anti-CD20-antibody and only 6% bendamustine [36]. A Spanish group reported improved survival in CLL patients younger than 70 years in Binet stage B and C between 1995-2004 suggesting that newer treatments are changing the prognosis of CLL [34].…”

Risk‐adapted bendamustine + rituximab is a tolerable treatment alternative for elderly patients with chronic lymphocytic leukaemia: a regional real‐world report on 141 consecutive Swedish patients

“…Our early sceening revealed, in line with Swedish CLL guidelines, that BR was the predominant first‐line therapy used in elderly in the time period studied and that chlorambucil was no longer commonly used in our region (Fig S1), in contrast to an earlier time period, i.e. before bendamustine was generally available 18 . Approval of the Ethics committee was obtained before commencement of the study.…”

“…Referrals from outside rarely occur and each patient file can be identified and used for in‐depth analysis. Thus, we have an optimal chance to obtain reliable real‐world data on consecutive patients treated in routine clinical care 18 …”