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

B. Lowenberg; T. Pabst; J. Maertens; P. Gradowska; B.J. Biemond; O. Spertini; E. Vellenga; L. Griskevicius; L.W. Tick; M. Jongen-Lavrencic; M.V. Kooy; M.C. Vekemans; W.J.F.M. van der Velden; B. Beverloo; L. Michaux; C. Graux; D. Deeren; O. de Weerdt; J.W.J. van Esser; M. Bargetzi; S.K. Klein; A. Gadisseur; P.E. Westerweel; H. Veelken; M. Gregor; T. Silzle; D. Van Lammeren-Venema; I. Moors; D.A. Breems; M. Hoogendoorn; M.C.J.C. Legdeur; T. Fischer; J. Kuball; J. Cornelissen; K. Porkka; G. Juliusson; P. Meyer; M. Hoglund; B.T. Gjertsen; J.J.W.M. Janssen; G. Huls; J. Passweg; J. Cloos; P.J.M. Valk; C.H.M.J. van Elssen; M.G. Manz; Y. Floisand; G.J. Ossenkoppele; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research (SAKK)

doi:10.1182/bloodadvances.2020003855

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

B. Lowenberg^*, T. Pabst, J. Maertens, P. Gradowska, B.J. Biemond, O. Spertini, E. Vellenga, L. Griskevicius, L.W. Tick, M. Jongen-Lavrencic, M.V. Kooy, M.C. Vekemans, W.J.F.M. van der Velden, B. Beverloo, L. Michaux, C. Graux, D. Deeren, O. de Weerdt, J.W.J. van Esser, M. BargetziS.K. Klein, A. Gadisseur, P.E. Westerweel, H. Veelken, M. Gregor, T. Silzle, D. Van Lammeren-Venema, I. Moors, D.A. Breems, M. Hoogendoorn, M.C.J.C. Legdeur, T. Fischer, J. Kuball, J. Cornelissen, K. Porkka, G. Juliusson, P. Meyer, M. Hoglund, B.T. Gjertsen, J.J.W.M. Janssen, G. Huls, J. Passweg, J. Cloos, P.J.M. Valk, C.H.M.J. van Elssen, M.G. Manz, Y. Floisand, G.J. Ossenkoppele, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK)

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	1110-1121
Number of pages	12
Journal	Blood advances
Volume	5
Issue number	4
DOIs	https://doi.org/10.1182/bloodadvances.2020003855
Publication status	Published - 23 Feb 2021

Keywords

ACUTE MYELOID-LEUKEMIA
HIGH-DOSE LENALIDOMIDE
AZACITIDINE PLUS LENALIDOMIDE
MINIMAL RESIDUAL DISEASE
SEQUENTIAL AZACITIDINE
ELDERLY-PATIENTS
COMBINATION
CYTARABINE

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10.1182/bloodadvances.2020003855

Cite this

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., van der Velden, W. J. F. M., Beverloo, B., Michaux, L., Graux, C., Deeren, D., de Weerdt, O., van Esser, J. W. J., ... Swiss Group for Clinical Cancer Research (SAKK) (2021). Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood advances, 5(4), 1110-1121. https://doi.org/10.1182/bloodadvances.2020003855

@article{3378c4797c354be5985d98af71849a68,

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

abstract = "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.",

keywords = "ACUTE MYELOID-LEUKEMIA, HIGH-DOSE LENALIDOMIDE, AZACITIDINE PLUS LENALIDOMIDE, MINIMAL RESIDUAL DISEASE, SEQUENTIAL AZACITIDINE, ELDERLY-PATIENTS, COMBINATION, CYTARABINE",

author = "B. Lowenberg and T. Pabst and J. Maertens and P. Gradowska and B.J. Biemond and O. Spertini and E. Vellenga and L. Griskevicius and L.W. Tick and M. Jongen-Lavrencic and M.V. Kooy and M.C. Vekemans and {van der Velden}, W.J.F.M. and B. Beverloo and L. Michaux and C. Graux and D. Deeren and {de Weerdt}, O. and {van Esser}, J.W.J. and M. Bargetzi and S.K. Klein and A. Gadisseur and P.E. Westerweel and H. Veelken and M. Gregor and T. Silzle and {Van Lammeren-Venema}, D. and I. Moors and D.A. Breems and M. Hoogendoorn and M.C.J.C. Legdeur and T. Fischer and J. Kuball and J. Cornelissen and K. Porkka and G. Juliusson and P. Meyer and M. Hoglund and B.T. Gjertsen and J.J.W.M. Janssen and G. Huls and J. Passweg and J. Cloos and P.J.M. Valk and {van Elssen}, C.H.M.J. and M.G. Manz and Y. Floisand and G.J. Ossenkoppele and {Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)} and {Swiss Group for Clinical Cancer Research (SAKK)}",

year = "2021",

month = feb,

day = "23",

doi = "10.1182/bloodadvances.2020003855",

language = "English",

volume = "5",

pages = "1110--1121",

journal = "Blood advances",

issn = "2473-9529",

publisher = "The American Society of Hematology",

number = "4",

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Lowenberg, B, Pabst, T, Maertens, J, Gradowska, P, Biemond, BJ, Spertini, O, Vellenga, E, Griskevicius, L, Tick, LW, Jongen-Lavrencic, M, Kooy, MV, Vekemans, MC, van der Velden, WJFM, Beverloo, B, Michaux, L, Graux, C, Deeren, D, de Weerdt, O, van Esser, JWJ, Bargetzi, M, Klein, SK, Gadisseur, A, Westerweel, PE, Veelken, H, Gregor, M, Silzle, T, Van Lammeren-Venema, D, Moors, I, Breems, DA, Hoogendoorn, M, Legdeur, MCJC, Fischer, T, Kuball, J, Cornelissen, J, Porkka, K, Juliusson, G, Meyer, P, Hoglund, M, Gjertsen, BT, Janssen, JJWM, Huls, G, Passweg, J, Cloos, J, Valk, PJM, van Elssen, CHMJ, Manz, MG, Floisand, Y, Ossenkoppele, GJ, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) & Swiss Group for Clinical Cancer Research (SAKK) 2021, 'Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial', Blood advances, vol. 5, no. 4, pp. 1110-1121. https://doi.org/10.1182/bloodadvances.2020003855

TY - JOUR

T1 - Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

AU - Lowenberg, B.

AU - Pabst, T.

AU - Maertens, J.

AU - Gradowska, P.

AU - Biemond, B.J.

AU - Spertini, O.

AU - Vellenga, E.

AU - Griskevicius, L.

AU - Tick, L.W.

AU - Jongen-Lavrencic, M.

AU - Kooy, M.V.

AU - Vekemans, M.C.

AU - van der Velden, W.J.F.M.

AU - Beverloo, B.

AU - Michaux, L.

AU - Graux, C.

AU - Deeren, D.

AU - de Weerdt, O.

AU - van Esser, J.W.J.

AU - Bargetzi, M.

AU - Klein, S.K.

AU - Gadisseur, A.

AU - Westerweel, P.E.

AU - Veelken, H.

AU - Gregor, M.

AU - Silzle, T.

AU - Van Lammeren-Venema, D.

AU - Moors, I.

AU - Breems, D.A.

AU - Hoogendoorn, M.

AU - Legdeur, M.C.J.C.

AU - Fischer, T.

AU - Kuball, J.

AU - Cornelissen, J.

AU - Porkka, K.

AU - Juliusson, G.

AU - Meyer, P.

AU - Hoglund, M.

AU - Gjertsen, B.T.

AU - Janssen, J.J.W.M.

AU - Huls, G.

AU - Passweg, J.

AU - Cloos, J.

AU - Valk, P.J.M.

AU - van Elssen, C.H.M.J.

AU - Manz, M.G.

AU - Floisand, Y.

AU - Ossenkoppele, G.J.

AU - Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)

AU - Swiss Group for Clinical Cancer Research (SAKK)

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.

KW - ACUTE MYELOID-LEUKEMIA

KW - HIGH-DOSE LENALIDOMIDE

KW - AZACITIDINE PLUS LENALIDOMIDE

KW - MINIMAL RESIDUAL DISEASE

KW - SEQUENTIAL AZACITIDINE

KW - ELDERLY-PATIENTS

KW - COMBINATION

KW - CYTARABINE

U2 - 10.1182/bloodadvances.2020003855

DO - 10.1182/bloodadvances.2020003855

M3 - Article

C2 - 33616652

SN - 2473-9529

VL - 5

SP - 1110

EP - 1121

JO - Blood advances

JF - Blood advances

IS - 4

ER -