Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation

Peter A. Riedell; Mehdi Hamadani; Kwang W. Ahn; Carlos Litovich; Claudio G. Brunstein; Amanda F. Cashen; Jonathon B. Cohen; Narendranath Epperla; Brian T. Hill; Annie Im; David J. Inwards; John Lister; John M. McCarty; Sai Ravi Kiran Pingali; Mazyar Shadman; Paul Shaughnessy; Melhem Solh; Patrick J. Stiff; Julie M. Vose; Mohamed A. Kharfan-Dabaja; Alex F. Herrera; Craig S. Sauter; Sonali M. Smith

doi:10.1111/bjh.17865

Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation

Peter A. Riedell, Mehdi Hamadani, Kwang W. Ahn, Carlos Litovich, Claudio G. Brunstein, Amanda F. Cashen, Jonathon B. Cohen, Narendranath Epperla, Brian T. Hill, Annie Im, David J. Inwards, John Lister, John M. McCarty, Sai Ravi Kiran Pingali, Mazyar Shadman, Paul Shaughnessy, Melhem Solh, Patrick J. Stiff, Julie M. Vose, Mohamed A. Kharfan-DabajaAlex F. Herrera, Craig S. Sauter, Sonali M. Smith

Medicine - Hematology, Oncology, Transplant

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

4 Scopus citations

Abstract

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

Original language	English (US)
Pages (from-to)	757-763
Number of pages	7
Journal	British journal of haematology
Volume	195
Issue number	5
Early online date	Sep 28 2021
DOIs	https://doi.org/10.1111/bjh.17865
State	Published - Dec 2021

Bibliographical note

Funding Information:
The 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 (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014‐20‐1‐2705 and N00014‐20‐1‐2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Accenture; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Astellas Pharma US; bluebird bio, inc.; Bristol‐Myers Squibb Co.; CareDx; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida Cell, Ltd.; Genentech Inc; Gilead; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncopeptides, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV.

Publisher Copyright:
© 2021 British Society for Haematology and John Wiley & Sons Ltd.

Keywords

autologous transplant
dynamic landmark analysis
mantle cell lymphoma
time to relapse

UN SDGs

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

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10.1111/bjh.17865

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Riedell, P. A., Hamadani, M., Ahn, K. W., Litovich, C., Brunstein, C. G., Cashen, A. F., Cohen, J. B., Epperla, N., Hill, B. T., Im, A., Inwards, D. J., Lister, J., McCarty, J. M., Ravi Kiran Pingali, S., Shadman, M., Shaughnessy, P., Solh, M., Stiff, P. J., Vose, J. M., ... Smith, S. M. (2021). Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation. British journal of haematology, 195(5), 757-763. https://doi.org/10.1111/bjh.17865

Riedell, PA, Hamadani, M, Ahn, KW, Litovich, C, Brunstein, CG, Cashen, AF, Cohen, JB, Epperla, N, Hill, BT, Im, A, Inwards, DJ, Lister, J, McCarty, JM, Ravi Kiran Pingali, S, Shadman, M, Shaughnessy, P, Solh, M, Stiff, PJ, Vose, JM, Kharfan-Dabaja, MA, Herrera, AF, Sauter, CS & Smith, SM 2021, 'Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation', British journal of haematology, vol. 195, no. 5, pp. 757-763. https://doi.org/10.1111/bjh.17865

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title = "Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation",

abstract = "In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.",

keywords = "autologous transplant, dynamic landmark analysis, mantle cell lymphoma, time to relapse",

author = "Riedell, {Peter A.} and Mehdi Hamadani and Ahn, {Kwang W.} and Carlos Litovich and Brunstein, {Claudio G.} and Cashen, {Amanda F.} and Cohen, {Jonathon B.} and Narendranath Epperla and Hill, {Brian T.} and Annie Im and Inwards, {David J.} and John Lister and McCarty, {John M.} and {Ravi Kiran Pingali}, Sai and Mazyar Shadman and Paul Shaughnessy and Melhem Solh and Stiff, {Patrick J.} and Vose, {Julie M.} and Kharfan-Dabaja, {Mohamed A.} and Herrera, {Alex F.} and Sauter, {Craig S.} and Smith, {Sonali M.}",

note = "Funding Information: The 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 (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014‐20‐1‐2705 and N00014‐20‐1‐2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Accenture; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Astellas Pharma US; bluebird bio, inc.; Bristol‐Myers Squibb Co.; CareDx; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida Cell, Ltd.; Genentech Inc; Gilead; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncopeptides, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV. Publisher Copyright: {\textcopyright} 2021 British Society for Haematology and John Wiley & Sons Ltd.",

year = "2021",

month = dec,

doi = "10.1111/bjh.17865",

language = "English (US)",

volume = "195",

pages = "757--763",

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T1 - Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation

AU - Riedell, Peter A.

AU - Hamadani, Mehdi

AU - Ahn, Kwang W.

AU - Litovich, Carlos

AU - Brunstein, Claudio G.

AU - Cashen, Amanda F.

AU - Cohen, Jonathon B.

AU - Epperla, Narendranath

AU - Hill, Brian T.

AU - Im, Annie

AU - Inwards, David J.

AU - Lister, John

AU - McCarty, John M.

AU - Ravi Kiran Pingali, Sai

AU - Shadman, Mazyar

AU - Shaughnessy, Paul

AU - Solh, Melhem

AU - Stiff, Patrick J.

AU - Vose, Julie M.

AU - Kharfan-Dabaja, Mohamed A.

AU - Herrera, Alex F.

AU - Sauter, Craig S.

AU - Smith, Sonali M.

N1 - Funding Information: The 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 (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014‐20‐1‐2705 and N00014‐20‐1‐2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Accenture; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Astellas Pharma US; bluebird bio, inc.; Bristol‐Myers Squibb Co.; CareDx; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida Cell, Ltd.; Genentech Inc; Gilead; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncopeptides, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV. Publisher Copyright: © 2021 British Society for Haematology and John Wiley & Sons Ltd.

PY - 2021/12

Y1 - 2021/12

N2 - In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

AB - In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

KW - autologous transplant

KW - dynamic landmark analysis

KW - mantle cell lymphoma

KW - time to relapse

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Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation

Abstract

Bibliographical note

Keywords

UN SDGs

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