Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial
Journal Paper/Review - Jan 23, 2021
Ossenkoppele Gert J, Porkka Kimmo, Cornelissen Jan, Kuball Juergen, Fischer Thomas, Legdeur Marie-Cecile J C, Hoogendoorn Mels, Breems Dimitri A, Moors Ine, van Lammeren-Venema Daniëlle, Silzle Tobias, Juliusson Gunnar, Meyer Peter, Floisand Yngvar, Manz Markus G, van Elssen Catharina H M J, Valk Peter J M, Cloos Jacqueline, Passweg Jakob, Huls Gerwin, Janssen Jeroen J W M, Gjertsen Bjorn T, Höglund Martin, Gregor Michael, Veelken Hendrik, van Marwijk Kooy Marinus, Jongen-Lavrencic Mojca, Tick Lidwine W, Griskevicius Laimonas, Vellenga Edo, Spertini Olivier, Biemond Bart J, Gradowska Patrycja, Maertens Johan, Pabst Thomas, Vekemans Marie-Christiane, van der Velden Walter J F M, Westerweel Peter E, Gadisseur Alain, Klein Saskia K, Bargetzi Mario, van Esser Joost W J, de Weerdt Okke, Deeren Dries, Graux Carlos, Michaux Lucienne, Beverloo Berna, Löwenberg Bob
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.