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Chronic Lymphocytic Leukemia
Feasibility and efficacy of addition of individualized-dose lenalidomide to chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit patients with advanced chronic lymphocytic leukemia
Arnon P. Kater,1 Marinus H.J. van Oers,1 Yvette van Norden,2 Lina van der Straten,3 Julia Driessen,1 Ward F.M. Posthuma,4,5 Martin Schipperus,6 Martine E.D. Chamuleau,7 Marcel Nijland,8 Jeanette K. Doorduijn,9 Michel Van Gelder,10 Mels Hoogendoorn,11 Francien De Croon,12 Shulamiet Wittebol,13 J. Martijn Kerst,14 Erik W.A. Marijt,5 Reinier A.P. Raymakers,15 Martijn R. Schaafsma,16 Johan A. Dobber,17 Sabina Kersting6 and Mark-David Levin3 on behalf of the HOVON CLL study group
1Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center, Amsterdam; 2Department of Hematology - HOVON Data Center, Erasmus MC Cancer Institute, Rotterdam; 3Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht; 4Department of Internal Medicine, Reinier de Graaf Hospital, Delft; 5Department of Hematology, Leiden University Medical Center; 6Department of Hematology, Haga Hospital, the Hague; 7Department of Hematology, VU University Medical Center, Amsterdam; 8Department of Hematology, University Medical Center, Groningen; 9Department of Hematology, Erasmus MC Cancer Institute, Rotterdam; 10Department of Hematology, Maastricht University Medical Center; 11Department of Internal Medicine, Medical Center, Leeuwarden; 12Department of Internal Medicine, Ikazia Hospital, Rotterdam; 13Department of Internal Medicine, Gelderland Valley Hospital, Ede; 14Department of Medical Oncology, Antoni van Leeuwenhoek Hospital, Amsterdam; 15Department of Hematology, University Medical Center, Utrecht; 16Department of Hematology, Medical Spectrum Twente, Enschede and 17Laboratory Special Hematology, Academic Medical Center, Amsterdam, the Netherlands
ABSTRACT
Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lym- phocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m2 daily), rituximab (375 mg/m2 cycle 1 and 500 mg/m2 cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treat- ment with fludarabine, cyclophosphamide and rituximab. This was fol- lowed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression- free survival was 49 months, after a median follow-up time of 27 months. The 2- and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most com- mon hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free sur- vival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. EuraCT number: 2010-022294-34.
Ferrata Storti Foundation
Haematologica 2019 Volume 104(1):147-154
Correspondence:
a.p.kater@amc.uva.nl
Received: March 28, 2018. Accepted: August 9, 2018. Pre-published: August 16, 2018.
doi:10.3324/haematol.2018.193854
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/1/147
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