Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

Robert F. Cornell; Raphael Fraser; Luciano Costa; Stacey Goodman; Noel Estrada-Merly; Cindy Lee; Gerhard Hildebrandt; Usama Gergis; Nosha Farhadfar; César O. Freytes; Rammurti T. Kamble; Maxwell Krem; Robert A. Kyle; Hillard M. Lazarus; David I. Marks; Kenneth Meehan; Sagar S. Patel; Muthalagu Ramanathan; Richard F. Olsson; John L. Wagner; Shaji Kumar; Muzaffar H. Qazilbash; Ninah Shah; Parameswaran Hari; Anita D'Souza

doi:10.1016/j.jtct.2020.11.018

Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

Robert F. Cornell, Raphael Fraser, Luciano Costa, Stacey Goodman, Noel Estrada-Merly, Cindy Lee, Gerhard Hildebrandt, Usama Gergis, Nosha Farhadfar, César O. Freytes, Rammurti T. Kamble, Maxwell Krem, Robert A. Kyle, Hillard M. Lazarus, David I. Marks, Kenneth Meehan, Sagar S. Patel, Muthalagu Ramanathan, Richard F. Olsson, John L. WagnerShaji Kumar, Muzaffar H. Qazilbash, Ninah Shah, Parameswaran Hari, Anita D'Souza

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

10 Scopus citations

Abstract

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P <.01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P =.02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P <.01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P =.22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR],.43; 95% confidence interval [CI],.24 to.78; P <.01) and PFS (HR,.43; 95% CI,.26 to.72; P <.01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

Original language	English
Pages (from-to)	264.e1-264.e7
Journal	Transplantation and Cellular Therapy
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/j.jtct.2020.11.018
State	Published - Mar 2021

Bibliographical note

Funding Information:
This work was presented in part as a poster with discussion at the Annual Meeting of the American Society of Clinical Oncology, June 2020. Financial disclosure: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; U24HL138660 from the NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, the Medical College of Wisconsin, and the National Marrow Donor Program, as well as from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen Inc.; Angiocrine Bioscience; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co. Ltd.; Gamida-Cell, Ltd.; Genentech, Inc.; HistoGenetics, Inc.; Incyte Corp.; Janssen Biotech, Inc.; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corp.; Omeros Corp.; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics LLC; Sanofi Genzyme; Shire; Sobi, Inc.; Stemcyte; Takeda Pharma; Terumo BCT; Viracor Eurofins; Vor Bio Pharma; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. CIBMTR supports accessibility of research in accordance with the National Institutes of Health Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality. Author statement: R.F.C. L.C. S.G. S.K. M.H.Q. N.S. P.H. and A.D. designed the study, conducted the analysis, interpreted the analysis, and wrote the paper. R.F. and N.E.-M. conducted the biostatistical analysis. C.L. G.H. U.G. N.F. C.O.F. R.T.K. M.K. R.A.K. H.M.L. D.I.M. K.M. S.S.P. M.R. R.F.O. and J.L.W. interpreted the analysis and edited the paper. All authors approved the final draft.

Funding Information:
Financial disclosure: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; U24HL138660 from the NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, the Medical College of Wisconsin, and the National Marrow Donor Program, as well as from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen Inc.; Angiocrine Bioscience; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida-Cell, Ltd.; Genentech, Inc.; HistoGenetics, Inc.; Incyte Corp.; Janssen Biotech, Inc.; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corp.; Omeros Corp.; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics LLC; Sanofi Genzyme; Shire; Sobi, Inc.; Stemcyte; Takeda Pharma; Terumo BCT; Viracor Eurofins; Vor Bio Pharma; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. CIBMTR supports accessibility of research in accordance with the National Institutes of Health Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality.

Publisher Copyright:
© 2020 The American Society for Transplantation and Cellular Therapy

Keywords

Bone marrow transplant
Hem malignancies
Myeloma

ASJC Scopus subject areas

Immunology and Allergy
Molecular Medicine
Hematology
Cell Biology
Transplantation

Access to Document

10.1016/j.jtct.2020.11.018

Cite this

Cornell, R. F., Fraser, R., Costa, L., Goodman, S., Estrada-Merly, N., Lee, C., Hildebrandt, G., Gergis, U., Farhadfar, N., Freytes, C. O., Kamble, R. T., Krem, M., Kyle, R. A., Lazarus, H. M., Marks, D. I., Meehan, K., Patel, S. S., Ramanathan, M., Olsson, R. F., ... D'Souza, A. (2021). Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden. Transplantation and Cellular Therapy, 27(3), 264.e1-264.e7. https://doi.org/10.1016/j.jtct.2020.11.018

@article{1c5391382add40d3bfe1faba27f503b3,

title = "Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden",

abstract = "The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P <.01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P =.02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P <.01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P =.22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR],.43; 95% confidence interval [CI],.24 to.78; P <.01) and PFS (HR,.43; 95% CI,.26 to.72; P <.01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.",

keywords = "Bone marrow transplant, Hem malignancies, Myeloma",

author = "Cornell, {Robert F.} and Raphael Fraser and Luciano Costa and Stacey Goodman and Noel Estrada-Merly and Cindy Lee and Gerhard Hildebrandt and Usama Gergis and Nosha Farhadfar and Freytes, {C{\'e}sar O.} and Kamble, {Rammurti T.} and Maxwell Krem and Kyle, {Robert A.} and Lazarus, {Hillard M.} and Marks, {David I.} and Kenneth Meehan and Patel, {Sagar S.} and Muthalagu Ramanathan and Olsson, {Richard F.} and Wagner, {John L.} and Shaji Kumar and Qazilbash, {Muzaffar H.} and Ninah Shah and Parameswaran Hari and Anita D'Souza",

note = "Funding Information: This work was presented in part as a poster with discussion at the Annual Meeting of the American Society of Clinical Oncology, June 2020. Financial disclosure: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; U24HL138660 from the NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, the Medical College of Wisconsin, and the National Marrow Donor Program, as well as from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen Inc.; Angiocrine Bioscience; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co. Ltd.; Gamida-Cell, Ltd.; Genentech, Inc.; HistoGenetics, Inc.; Incyte Corp.; Janssen Biotech, Inc.; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corp.; Omeros Corp.; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics LLC; Sanofi Genzyme; Shire; Sobi, Inc.; Stemcyte; Takeda Pharma; Terumo BCT; Viracor Eurofins; Vor Bio Pharma; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. CIBMTR supports accessibility of research in accordance with the National Institutes of Health Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality. Author statement: R.F.C. L.C. S.G. S.K. M.H.Q. N.S. P.H. and A.D. designed the study, conducted the analysis, interpreted the analysis, and wrote the paper. R.F. and N.E.-M. conducted the biostatistical analysis. C.L. G.H. U.G. N.F. C.O.F. R.T.K. M.K. R.A.K. H.M.L. D.I.M. K.M. S.S.P. M.R. R.F.O. and J.L.W. interpreted the analysis and edited the paper. All authors approved the final draft. Funding Information: Financial disclosure: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; U24HL138660 from the NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, the Medical College of Wisconsin, and the National Marrow Donor Program, as well as from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen Inc.; Angiocrine Bioscience; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida-Cell, Ltd.; Genentech, Inc.; HistoGenetics, Inc.; Incyte Corp.; Janssen Biotech, Inc.; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corp.; Omeros Corp.; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics LLC; Sanofi Genzyme; Shire; Sobi, Inc.; Stemcyte; Takeda Pharma; Terumo BCT; Viracor Eurofins; Vor Bio Pharma; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. CIBMTR supports accessibility of research in accordance with the National Institutes of Health Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality. Publisher Copyright: {\textcopyright} 2020 The American Society for Transplantation and Cellular Therapy",

year = "2021",

month = mar,

doi = "10.1016/j.jtct.2020.11.018",

language = "English",

volume = "27",

pages = "264.e1--264.e7",

number = "3",

}

Cornell, RF, Fraser, R, Costa, L, Goodman, S, Estrada-Merly, N, Lee, C, Hildebrandt, G, Gergis, U, Farhadfar, N, Freytes, CO, Kamble, RT, Krem, M, Kyle, RA, Lazarus, HM, Marks, DI, Meehan, K, Patel, SS, Ramanathan, M, Olsson, RF, Wagner, JL, Kumar, S, Qazilbash, MH, Shah, N, Hari, P & D'Souza, A 2021, 'Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden', Transplantation and Cellular Therapy, vol. 27, no. 3, pp. 264.e1-264.e7. https://doi.org/10.1016/j.jtct.2020.11.018

Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden. / Cornell, Robert F.; Fraser, Raphael; Costa, Luciano et al.
In: Transplantation and Cellular Therapy, Vol. 27, No. 3, 03.2021, p. 264.e1-264.e7.

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

TY - JOUR

T1 - Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

AU - Cornell, Robert F.

AU - Fraser, Raphael

AU - Costa, Luciano

AU - Goodman, Stacey

AU - Estrada-Merly, Noel

AU - Lee, Cindy

AU - Hildebrandt, Gerhard

AU - Gergis, Usama

AU - Farhadfar, Nosha

AU - Freytes, César O.

AU - Kamble, Rammurti T.

AU - Krem, Maxwell

AU - Kyle, Robert A.

AU - Lazarus, Hillard M.

AU - Marks, David I.

AU - Meehan, Kenneth

AU - Patel, Sagar S.

AU - Ramanathan, Muthalagu

AU - Olsson, Richard F.

AU - Wagner, John L.

AU - Kumar, Shaji

AU - Qazilbash, Muzaffar H.

AU - Shah, Ninah

AU - Hari, Parameswaran

AU - D'Souza, Anita

N1 - Funding Information: This work was presented in part as a poster with discussion at the Annual Meeting of the American Society of Clinical Oncology, June 2020. Financial disclosure: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; U24HL138660 from the NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, the Medical College of Wisconsin, and the National Marrow Donor Program, as well as from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen Inc.; Angiocrine Bioscience; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co. Ltd.; Gamida-Cell, Ltd.; Genentech, Inc.; HistoGenetics, Inc.; Incyte Corp.; Janssen Biotech, Inc.; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corp.; Omeros Corp.; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics LLC; Sanofi Genzyme; Shire; Sobi, Inc.; Stemcyte; Takeda Pharma; Terumo BCT; Viracor Eurofins; Vor Bio Pharma; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. CIBMTR supports accessibility of research in accordance with the National Institutes of Health Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality. Author statement: R.F.C. L.C. S.G. S.K. M.H.Q. N.S. P.H. and A.D. designed the study, conducted the analysis, interpreted the analysis, and wrote the paper. R.F. and N.E.-M. conducted the biostatistical analysis. C.L. G.H. U.G. N.F. C.O.F. R.T.K. M.K. R.A.K. H.M.L. D.I.M. K.M. S.S.P. M.R. R.F.O. and J.L.W. interpreted the analysis and edited the paper. All authors approved the final draft. Funding Information: Financial disclosure: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; U24HL138660 from the NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St. Baldrick's Foundation, Stanford University, the Medical College of Wisconsin, and the National Marrow Donor Program, as well as from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen Inc.; Angiocrine Bioscience; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida-Cell, Ltd.; Genentech, Inc.; HistoGenetics, Inc.; Incyte Corp.; Janssen Biotech, Inc.; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corp.; Omeros Corp.; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics LLC; Sanofi Genzyme; Shire; Sobi, Inc.; Stemcyte; Takeda Pharma; Terumo BCT; Viracor Eurofins; Vor Bio Pharma; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. CIBMTR supports accessibility of research in accordance with the National Institutes of Health Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality. Publisher Copyright: © 2020 The American Society for Transplantation and Cellular Therapy

PY - 2021/3

Y1 - 2021/3

N2 - The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P <.01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P =.02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P <.01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P =.22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR],.43; 95% confidence interval [CI],.24 to.78; P <.01) and PFS (HR,.43; 95% CI,.26 to.72; P <.01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

AB - The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P <.01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P =.02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P <.01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P =.22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR],.43; 95% confidence interval [CI],.24 to.78; P <.01) and PFS (HR,.43; 95% CI,.26 to.72; P <.01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

KW - Bone marrow transplant

KW - Hem malignancies

KW - Myeloma

UR - http://www.scopus.com/inward/record.url?scp=85101183550&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85101183550&partnerID=8YFLogxK

U2 - 10.1016/j.jtct.2020.11.018

DO - 10.1016/j.jtct.2020.11.018

M3 - Article

C2 - 33781533

AN - SCOPUS:85101183550

SN - 2666-6367

VL - 27

SP - 264.e1-264.e7

JO - Transplantation and Cellular Therapy

JF - Transplantation and Cellular Therapy

IS - 3

ER -

Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden

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