Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

Melissa Alsina; Pamela S. Becker; Xiaobo Zhong; Alexia Adams; Parameswaran Hari; Scott Rowley; Edward A. Stadtmauer; David H. Vesole; Brent Logan; Daniel Weisdorf; Muzaffar Qazilbash; Leslie L. Popplewell; Brian McClune; William Bensinger; Marcie Riches; Sergio A. Giralt; Marcelo C. Pasquini

doi:10.1016/j.bbmt.2014.04.014

Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

Melissa Alsina, Pamela S. Becker, Xiaobo Zhong, Alexia Adams, Parameswaran Hari, Scott Rowley, Edward A. Stadtmauer, David H. Vesole, Brent Logan, Daniel Weisdorf, Muzaffar Qazilbash, Leslie L. Popplewell, Brian McClune, William Bensinger, Marcie Riches, Sergio A. Giralt, Marcelo C. Pasquini

Medicine - Hematology, Oncology, Transplant

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

81 Scopus citations

Abstract

Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach.

Original language	English (US)
Pages (from-to)	1183-1189
Number of pages	7
Journal	Biology of Blood and Marrow Transplantation
Volume	20
Issue number	8
DOIs	https://doi.org/10.1016/j.bbmt.2014.04.014
State	Published - Aug 2014

Bibliographical note

Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children’s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick’s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.

Funding Information:
We acknowledge additional support from the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research (CIBMTR) . Support provided by the NMDP was facilitated by the Department of the Navy, Office of Naval Research grants N00014-08-1-1207 , N00014-10-1-0204 , N00014-11-1-0339 , N00014-12-1-0142 and N00014-13-1-0039 . Any views, opinions, findings, conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the views or the official policy or position of the above mentioned parties. We thank the patients, physicians, nurses and research staffs at all participating centers.

Keywords

Allogeneic transplantation
Lenalidomide
Multiple myeloma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbmt.2014.04.014

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Alsina, M., Becker, P. S., Zhong, X., Adams, A., Hari, P., Rowley, S., Stadtmauer, E. A., Vesole, D. H., Logan, B., Weisdorf, D., Qazilbash, M., Popplewell, L. L., McClune, B., Bensinger, W., Riches, M., Giralt, S. A., & Pasquini, M. C. (2014). Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 20(8), 1183-1189. https://doi.org/10.1016/j.bbmt.2014.04.014

Alsina, M, Becker, PS, Zhong, X, Adams, A, Hari, P, Rowley, S, Stadtmauer, EA, Vesole, DH, Logan, B, Weisdorf, D, Qazilbash, M, Popplewell, LL, McClune, B, Bensinger, W, Riches, M, Giralt, SA & Pasquini, MC 2014, 'Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 20, no. 8, pp. 1183-1189. https://doi.org/10.1016/j.bbmt.2014.04.014

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title = "Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation",

abstract = "Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach.",

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author = "Melissa Alsina and Becker, {Pamela S.} and Xiaobo Zhong and Alexia Adams and Parameswaran Hari and Scott Rowley and Stadtmauer, {Edward A.} and Vesole, {David H.} and Brent Logan and Daniel Weisdorf and Muzaffar Qazilbash and Popplewell, {Leslie L.} and Brian McClune and William Bensinger and Marcie Riches and Giralt, {Sergio A.} and Pasquini, {Marcelo C.}",

note = "Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children{\textquoteright}s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick{\textquoteright}s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. Funding Information: We acknowledge additional support from the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research (CIBMTR) . Support provided by the NMDP was facilitated by the Department of the Navy, Office of Naval Research grants N00014-08-1-1207 , N00014-10-1-0204 , N00014-11-1-0339 , N00014-12-1-0142 and N00014-13-1-0039 . Any views, opinions, findings, conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the views or the official policy or position of the above mentioned parties. We thank the patients, physicians, nurses and research staffs at all participating centers. ",

year = "2014",

month = aug,

doi = "10.1016/j.bbmt.2014.04.014",

language = "English (US)",

volume = "20",

pages = "1183--1189",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier Inc.",

number = "8",

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TY - JOUR

T1 - Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

AU - Alsina, Melissa

AU - Becker, Pamela S.

AU - Zhong, Xiaobo

AU - Adams, Alexia

AU - Hari, Parameswaran

AU - Rowley, Scott

AU - Stadtmauer, Edward A.

AU - Vesole, David H.

AU - Logan, Brent

AU - Weisdorf, Daniel

AU - Qazilbash, Muzaffar

AU - Popplewell, Leslie L.

AU - McClune, Brian

AU - Bensinger, William

AU - Riches, Marcie

AU - Giralt, Sergio A.

AU - Pasquini, Marcelo C.

N1 - Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children’s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick’s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. Funding Information: We acknowledge additional support from the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research (CIBMTR) . Support provided by the NMDP was facilitated by the Department of the Navy, Office of Naval Research grants N00014-08-1-1207 , N00014-10-1-0204 , N00014-11-1-0339 , N00014-12-1-0142 and N00014-13-1-0039 . Any views, opinions, findings, conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the views or the official policy or position of the above mentioned parties. We thank the patients, physicians, nurses and research staffs at all participating centers.

PY - 2014/8

Y1 - 2014/8

N2 - Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach.

AB - Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach.

KW - Allogeneic transplantation

KW - Lenalidomide

KW - Multiple myeloma

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Lenalidomide Maintenance for High-Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

Abstract

Bibliographical note

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UN SDGs

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