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