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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.

Authors :
Kater AP
van Oers MHJ
van Norden Y
van der Straten L
Driessen J
Posthuma WFM
Schipperus M
Chamuleau MED
Nijland M
Doorduijn JK
Van Gelder M
Hoogendoorn M
De Croon F
Wittebol S
Kerst JM
Marijt EWA
Raymakers RAP
Schaafsma MR
Dobber JA
Kersting S
Levin MD
Source :
Haematologica [Haematologica] 2019 Jan; Vol. 104 (1), pp. 147-154. Date of Electronic Publication: 2018 Aug 16.
Publication Year :
2019

Abstract

Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic 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/m <superscript>2</superscript> daily), rituximab (375 mg/m <superscript>2</superscript> cycle 1 and 500 mg/m <superscript>2</superscript> 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 treatment with fludarabine, cyclophosphamide and rituximab. This was followed 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 common 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 survival 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 .<br /> (Copyright© 2019 Ferrata Storti Foundation.)

Details

Language :
English
ISSN :
1592-8721
Volume :
104
Issue :
1
Database :
MEDLINE
Journal :
Haematologica
Publication Type :
Academic Journal
Accession number :
30115656
Full Text :
https://doi.org/10.3324/haematol.2018.193854