TY - JOUR
T1 - Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML
T2 - the HOVON-SAKK-132 trial
AU - Löwenberg, Bob
AU - Pabst, Thomas
AU - Maertens, Johan
AU - Gradowska, Patrycja
AU - Biemond, Bart J
AU - Spertini, Olivier
AU - Vellenga, Edo
AU - Griskevicius, Laimonas
AU - Tick, Lidwine W
AU - Jongen-Lavrencic, Mojca
AU - van Marwijk Kooy, Marinus
AU - Vekemans, Marie-Christiane
AU - van der Velden, Walter J F M
AU - Beverloo, Berna
AU - Michaux, Lucienne
AU - Graux, Carlos
AU - Deeren, Dries
AU - de Weerdt, Okke
AU - van Esser, Joost W J
AU - Bargetzi, Mario
AU - Klein, Saskia K
AU - Gadisseur, Alain
AU - Westerweel, Peter E
AU - Veelken, Hendrik
AU - Gregor, Michael
AU - Silzle, Tobias
AU - van Lammeren-Venema, Daniëlle
AU - Moors, Ine
AU - Breems, Dimitri A
AU - Hoogendoorn, Mels
AU - Legdeur, Marie-Cecile J C
AU - Fischer, Thomas
AU - Kuball, Juergen
AU - Cornelissen, Jan
AU - Porkka, Kimmo
AU - Juliusson, Gunnar
AU - Meyer, Peter
AU - Höglund, Martin
AU - Gjertsen, Bjorn T
AU - Janssen, Jeroen J W M
AU - Huls, Gerwin
AU - Passweg, Jakob
AU - Cloos, Jacqueline
AU - Valk, Peter J M
AU - van Elssen, Catharina H M J
AU - Manz, Markus G
AU - Floisand, Yngvar
AU - Ossenkoppele, Gert J
N1 - © 2021 by The American Society of Hematology.
PY - 2021/2/23
Y1 - 2021/2/23
N2 - 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.
AB - 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.
U2 - 10.1182/bloodadvances.2020003855
DO - 10.1182/bloodadvances.2020003855
M3 - Article
C2 - 33616652
VL - 5
SP - 1110
EP - 1121
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -