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Haematologica. 2019 Oct 3. pii: haematol.2019.220194. doi: 10.3324/haematol.2019.220194. [Epub ahead of print]

IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: a Danish nationwide population-based study.

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Department of Hematology, Odense University Hospital.
Department of Epidemiology Research, Statens Serum institut.
Department of Epidemiology Research, Statens Serum Institut.
Department of Hematology, Rigshospitalet.
Department of Hematology, Zealand University Hospital.
Department of Hematology, Herlev Hospital.
Department of Hematology, Rigshospitalet;


Patients with chronic lymphocytic leukemia and immunoglobulin heavy-chain variable region gene unmutated status have inferior survival from time of treatment in clinical studies. We assessed real-world outcomes based on mutational status and treatment regimen in a nationwide population-based cohort, comprising all 4135 patients from the Danish chronic lymphocytic leukemia registry diagnosed between 2008 and 2017. In total, 850 patients with known mutational status received treatment: 42% of patients received intensive chemoimmunotherapy treatment consisting of fludarabine, cyclophosphamide plus rituximab, or bendamustine plus rituximab; 27% received chlorambucil in combination with anti-CD20 antibodies or as monotherapy, and 31% received other, less common, treatments. No difference in overall survival from time of first treatment according to mutational status was observed, while treatment-free survival from start of first treatment was inferior for unmutated patients. The median treatment-free survival was 2.5 years for patients treated with chlorambucil plus anti-CD20, and 1 year for chlorambucil monotherapy. The 3-year treatment-free survival for fludarabine, cyclophosphamide plus rituximab-, and bendamustine plus rituximab-treated patients was 90% and 91% for mutated, and 76% and 53% for unmutated patients respectively, and the 3-year overall survival was similar for the two regimens (86-88%). Thus, it appears that patients progressing after intensive chemoimmunotherapy as first line therapy can be rescued by subsequent treatment, without jeopardizing long overall survival, in the real-world setting. Intensive chemoimmunotherapy remains a legitimate option alongside targeted agents, and part of a personalized treatment landscape in chronic lymphocytic leukemia, while improved supportive care and treatment options are warranted for unfit patients.


Chronic Lymphocytic Leukemia; Clinical and Molecular Epidemiology; Lymphoproliferative Disorders

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