Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

Bob Löwenberg*, Thomas Pabst, Johan Maertens, Patrycja Gradowska, Bart J Biemond, Olivier Spertini, Edo Vellenga, Laimonas Griskevicius, Lidwine W Tick, Mojca Jongen-Lavrencic, Marinus van Marwijk Kooy, Marie-Christiane Vekemans, Walter J F M van der Velden, Berna Beverloo, Lucienne Michaux, Carlos Graux, Dries Deeren, Okke de Weerdt, Joost W J van Esser, Mario BargetziSaskia K Klein, Alain Gadisseur, Peter E Westerweel, Hendrik Veelken, Michael Gregor, Tobias Silzle, Daniëlle van Lammeren-Venema, Ine Moors, Dimitri A Breems, Mels Hoogendoorn, Marie-Cecile J C Legdeur, Thomas Fischer, Juergen Kuball, Jan Cornelissen, Kimmo Porkka, Gunnar Juliusson, Peter Meyer, Martin Höglund, Bjorn T Gjertsen, Jeroen J W M Janssen, Gerwin Huls, Jakob Passweg, Jacqueline Cloos, Peter J M Valk, Catharina H M J van Elssen, Markus G Manz, Yngvar Floisand, Gert J Ossenkoppele

*Corresponding author for this work

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Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.

Original languageEnglish
Pages (from-to)1110-1121
Number of pages12
Issue number4
Publication statusPublished - 23-Feb-2021

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