Page 163 - Haematologica - Vol. 105 n. 6 - June 2020

Chronic Lymphocytic Leukemia
IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: a Danish nationwide population-based study
Emelie Curovic Rotbain,1,2,3,4 Henrik Frederiksen,1,3,5 Henrik Hjalgrim,2,4 Klaus Rostgaard,4 Gudrun Jakubsdottir Egholm,1 Banafsheh Zahedi,2 Christian Bjørn Poulsen,6 Lisbeth Enggard,7 Caspar da Cunha-Bang#2 and Carsten Utoft Niemann#2
1Department of Hematology, Odense University Hospital, Odense; 2Department of Hematology, Rigshospitalet, Copenhagen; 3Department of Clinical Research, University of Southern Denmark, Odense; 4Department of Epidemiology Research, Statens Serum Institut, Copenhagen; 5Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense; 6Department of Hematology, Zealand University Hospital, Roskilde and 7Department of Hematology, Herlev Hospital, Herlev, Denmark.
#CdC-B and CU contributed equally as co-senior authors.
ABSTRACT
Patients with chronic lymphocytic leukemia and unmutated immunoglobulin heavy-chain variable region gene (IGHV) 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 4,135 patients from the Danish chronic lymphocytic leukemia registry diagnosed between 2008 and 2017. In total, 850 patients with known mutational status received treat- ment: 42% of patients received intensive chemoimmunotherapy consisting of fludarabine, cyclophosphamide plus rituximab, or bendamustine plus rit- uximab; 27% received chlorambucil in combination with anti-CD20 anti- bodies or as monotherapy, and 31% received other, less common treat- ments. No difference in overall survival from time of first treatment accord- ing to mutational status was observed, while treatment-free survival from start of first treatment was inferior for patients with unmutated IGHV. The median treatment-free survival was 2.5 years for patients treated with chlo- rambucil plus anti-CD20, and 1 year for those who received chlorambucil monotherapy. The 3-year treatment-free survival rates for patients treated with fludarabine, cyclophosphamide plus rituximab, and bendamustine plus rituximab were 90% and 91% for those with mutated IGHV, and 76% and 53% for those with unmutated IGHV, respectively, and the 3-year overall survival rates were similar for the two regimens (86-88%). Thus, it appears that, in the real-world setting, patients progressing after intensive chemoim- munotherapy as first-line therapy can be rescued by subsequent treatment, without jeopardizing their long overall survival. Intensive chemoim- munotherapy 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.
Introduction
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world and half of the patients with this condition require treatment within 5 years of diagnosis.1 According to Danish national CLL guidelines,2,3 stan- dard first-line treatment includes fludarabine, cyclophosphamide plus rituximab (FCR) for younger, fit patients,4,5 and bendamustine plus rituximab (BR) for patients above 65 years old.6,7 Furthermore, chlorambucil, either as monotherapy or com-
Ferrata Storti Foundation
Haematologica 2020 Volume 105(6):1621-1629
Correspondence:
CARSTEN UTOFT NIEMANN
carsten.utoft.niemann@regionh.dk
Received: February 22, 2019. Accepted: September 26, 2019. Pre-published: October 3, 2019.
doi:10.3324/haematol.2019.220194
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/6/1621
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