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

Lowenberg, B.; Pabst, T.; Maertens, J.; Gradowska, P.; Biemond, B.J.; Spertini, O.; ... ; Swiss Grp Clinical Canc Res SAKK (2021)

Article / Letter to editor

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.

• All authors: Lowenberg, B.; Pabst, T.; Maertens, J.; Gradowska, P.; Biemond, B.J.; Spertini, O.; Vellenga, E.; Griskevicius, L.; Tick, L.W.; Jongen-Lavrencic, M.; Kooy, M.V.; Vekemans, M.C.; Velden, W.J.F.M. van der; Beverloo, B.; Michaux, L.; Graux, C.; Deeren, D.; Weerdt, O. de; Esser, J.W.J. van; Bargetzi, M.; Klein, S.K.; Gadisseur, A.; Westerweel, P.E.; Veelken, H.; Gregor, M.; Silzle, T.; Lammeren-Venema, D. van; Moors, I.; Breems, D.A.; Hoogendoorn, M.; Legdeur, M.C.J.C.; Fischer, T.; Kuball, J.; Cornelissen, J.; Porkka, K.; Juliusson, G.; Meyer, P.; Hoglund, M.; Gjertsen, B.T.; Janssen, J.J.W.M.; Huls, G.; Passweg, J.; Cloos, J.; Valk, P.J.M.; Elssen, C.H.M.J. van; Manz, M.G.; Floisand, Y.; Ossenkoppele, G.J.; Dutch-Belgian Hemato-Oncology Coop; Swiss Grp Clinical Canc Res SAKK
• Date: 2021-02-23
• Journal: Blood Advances
• Volume: 5
• Issue: 4
• Pages: 1110 - 1121
• DOI: doi:10.1182/bloodadvances.2020003855
• Link: https://ashpublications.org/bloodadvances/article-pdf/5/4/1110/1800710/a...