The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy

Marta Garcia-Recio; Kitsada Wudhikarn; Martina Pennisi; Rosalia Alonso-Trillo; Jessica Flynn; Roni Shouval; Aishat O. Afuye; Mari Lynne Silverberg; Connie W. Batlevi; Parastoo Dahi; Sean Devlin; Sergio A. Giralt; Elizabeth Halton; Josel Ruiz; Molly Maloy; Elena Mead; M. Lia Palomba; Bianca Santomasso; Craig S. Sauter; Michael Scordo; Gunjan L. Shah; Miguel Angel Perales

doi:10.1016/j.jtct.2020.10.022

The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy

Marta Garcia-Recio
, Kitsada Wudhikarn
, Martina Pennisi
, Rosalia Alonso-Trillo
, Jessica Flynn
, Roni Shouval
, Aishat O. Afuye
, Mari Lynne Silverberg
, Connie W. Batlevi
, Parastoo Dahi
, Sean Devlin
, Sergio A. Giralt
, Elizabeth Halton
, Josel Ruiz
, Molly Maloy
, Elena Mead
, M. Lia Palomba
, Bianca Santomasso
, Craig S. Sauter
, Michael Scordo

Gunjan L. Shah, Miguel Angel Perales

Memorial Sloan-Kettering Cancer Center
Chulalongkorn University
University of Milan
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
Hospital Universitario Puerta de Hierro Majadahonda
Cornell University

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

48 Scopus citations

Abstract

CD19-targeted chimeric antigen receptor (CAR) T cells have shown excellent activity against relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). CAR T cell therapy is associated with early toxicities, including cytokine release syndrome and neurotoxicity. The incidence and severity of these toxicities has been associated in part with baseline disease and patient characteristics, which also may impact overall survival (OS) and progression-free survival (PFS). However, there are limited data on patient selection and how to better predict toxicities or outcomes. Indexes used in patients with DLBCL, such as the International Prognostic Index (IPI and age-adjusted IPI [aaIPI]) and in transplantation recipients, such as the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), have not been evaluated in this setting. Here we evaluated 4 indices— IPI, aaIPI, HCT-CI, and the Charlson Comorbidity Index (CCI)—and their associations with early CAR T cell related-toxicities and outcomes. We demonstrated an association between high-risk IPI or aaIPI and inferior PFS in patients with R/R DLBCL treated with CAR T cell therapy. We also found an association between aaIPI and IPI with OS and neurotoxicity, respectively. CCI was not associated with toxicities or outcomes, and owing to the small sample size, we could not draw a conclusion regarding associations with the HCT-CI. Both the IPI and aaIPI are widely used tools that can now provide better information to guide selection of patients who would best benefit from CD19 CAR T cell therapy.

Original language	English
Pages (from-to)	233-240
Number of pages	8
Journal	Transplantation and Cellular Therapy
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/j.jtct.2020.10.022
State	Published - Mar 2021
Externally published	Yes

Bibliographical note

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

Funding

Financial disclosure: This work was supported by the National Institutes of Health (NIH), National Cancer Institute Cancer Center Support Grant P30CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. K.W. has received salary support from the Parker Institute of Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center. M.P. was supported by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship and by Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Financial disclosure: This work was supported by the National Institutes of Health (NIH), National Cancer Institute Cancer Center Support Grant P30CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. K.W. has received salary support from the Parker Institute of Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center. M.P. was supported by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship and by Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS. Conflict of interest statement: M.G.R. has received honoraria from Janssen and Takeda. P.D. has served as a paid consultant on advisory boards for Kite. C.W.B. has received research support from Janssen, Novartis, Epizyme, Xynomics, and Bayer. She has served as a paid consultant on advisory boards for Life Sci, GLG, Juno/Celgene, Seattle Genetics, and Kite. She received honoraria from Dava Oncology. S.G. has received consultant fees and honoraria related to speakers’ bureau activities from Celgene, Genzyme, and Millennium Pharmaceuticals. L.P. is on the advisory committee of Pharmacyclics and provide consultancy for Noble Insights. B.S. has consulted for Kite/Gilead, Juno/Celgene, and Novartis. C.S.S. has served as a paid consultant on advisory boards for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/Gilead, Celgene, Gamida Cell, and GSK. He has received research funds for clinical trials from Juno Therapeutics, Celgene, Precision Biosciences, and Sanofi-Genzyme. M.S. is a consultant for McKinsey & Company and Angiocrine Bioscience. S.G. has received research support from Amgen and Janssen. M.A.P. reports honoraria from Abbvie, Astellas, Bristol-Myers Squibb, Celgene, Incyte, Karyopharm, Kite/Gilead, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. He serves on data safety and monitoring boards for Servier and Medigene and the scientific advisory boards of MolMed and NexImmune. He has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec. He serves in a volunteer capacity as a member of the board of directors of the American Society for Transplantation and Cellular Therapy and Be the Match (National Marrow Donor Program), as well as on the CIBMTR Cellular Immunotherapy Data Resource Committee. K.W. M.P. R.A.T. J.F. R.S. A.O.A, M.L.S. S.D. E.H. J.R. M.M. and E.M. have no relevant conflicts of interest to report.

Funders	Funder number
Associazione italiana contro le leucemie-linfomi e mieloma Milano e Provincia ONLUS
CIBMTR Cellular Immunotherapy Data Resource Committee
GLG
McKinsey & Company and Angiocrine Bioscience
National Cancer Institute Cancer Center Support
National Institutes of Health
National Cancer Institute	P30CA008748
Amgen
Bristol-Myers Squibb
Astellas Pharma US
Merck
Novartis
American-Italian Cancer Foundation
AbbVie
Janssen Pharmaceuticals
Parker Institute for Cancer Immunotherapy
Bayer Fund
American Society for Transplantation and Cellular Therapy
Miltenyi Biotec

Keywords

Cellular therapy
Chimeric antigen receptor T cells
International Prognostic Index
Non-Hodgkin lymphoma

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10.1016/j.jtct.2020.10.022

Cite this

Garcia-Recio, M., Wudhikarn, K., Pennisi, M., Alonso-Trillo, R., Flynn, J., Shouval, R., Afuye, A. O., Silverberg, M. L., Batlevi, C. W., Dahi, P., Devlin, S., Giralt, S. A., Halton, E., Ruiz, J., Maloy, M., Mead, E., Palomba, M. L., Santomasso, B., Sauter, C. S., ... Perales, M. A. (2021). The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy. Transplantation and Cellular Therapy, 27(3), 233-240. https://doi.org/10.1016/j.jtct.2020.10.022

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title = "The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy",

abstract = "CD19-targeted chimeric antigen receptor (CAR) T cells have shown excellent activity against relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). CAR T cell therapy is associated with early toxicities, including cytokine release syndrome and neurotoxicity. The incidence and severity of these toxicities has been associated in part with baseline disease and patient characteristics, which also may impact overall survival (OS) and progression-free survival (PFS). However, there are limited data on patient selection and how to better predict toxicities or outcomes. Indexes used in patients with DLBCL, such as the International Prognostic Index (IPI and age-adjusted IPI [aaIPI]) and in transplantation recipients, such as the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), have not been evaluated in this setting. Here we evaluated 4 indices{\textemdash} IPI, aaIPI, HCT-CI, and the Charlson Comorbidity Index (CCI){\textemdash}and their associations with early CAR T cell related-toxicities and outcomes. We demonstrated an association between high-risk IPI or aaIPI and inferior PFS in patients with R/R DLBCL treated with CAR T cell therapy. We also found an association between aaIPI and IPI with OS and neurotoxicity, respectively. CCI was not associated with toxicities or outcomes, and owing to the small sample size, we could not draw a conclusion regarding associations with the HCT-CI. Both the IPI and aaIPI are widely used tools that can now provide better information to guide selection of patients who would best benefit from CD19 CAR T cell therapy.",

keywords = "Cellular therapy, Chimeric antigen receptor T cells, International Prognostic Index, Non-Hodgkin lymphoma",

author = "Marta Garcia-Recio and Kitsada Wudhikarn and Martina Pennisi and Rosalia Alonso-Trillo and Jessica Flynn and Roni Shouval and Afuye, \{Aishat O.\} and Silverberg, \{Mari Lynne\} and Batlevi, \{Connie W.\} and Parastoo Dahi and Sean Devlin and Giralt, \{Sergio A.\} and Elizabeth Halton and Josel Ruiz and Molly Maloy and Elena Mead and Palomba, \{M. Lia\} and Bianca Santomasso and Sauter, \{Craig S.\} and Michael Scordo and Shah, \{Gunjan L.\} and Perales, \{Miguel Angel\}",

note = "Publisher Copyright: {\textcopyright} 2020 The American Society for Transplantation and Cellular Therapy",

year = "2021",

month = mar,

doi = "10.1016/j.jtct.2020.10.022",

language = "אנגלית",

volume = "27",

pages = "233--240",

journal = "Transplantation and Cellular Therapy",

issn = "2666-6375",

publisher = "Elsevier BV",

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Garcia-Recio, M, Wudhikarn, K, Pennisi, M, Alonso-Trillo, R, Flynn, J, Shouval, R, Afuye, AO, Silverberg, ML, Batlevi, CW, Dahi, P, Devlin, S, Giralt, SA, Halton, E, Ruiz, J, Maloy, M, Mead, E, Palomba, ML, Santomasso, B, Sauter, CS, Scordo, M, Shah, GL & Perales, MA 2021, 'The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy', Transplantation and Cellular Therapy, vol. 27, no. 3, pp. 233-240. https://doi.org/10.1016/j.jtct.2020.10.022

TY - JOUR

T1 - The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy

AU - Garcia-Recio, Marta

AU - Wudhikarn, Kitsada

AU - Pennisi, Martina

AU - Alonso-Trillo, Rosalia

AU - Flynn, Jessica

AU - Shouval, Roni

AU - Afuye, Aishat O.

AU - Silverberg, Mari Lynne

AU - Batlevi, Connie W.

AU - Dahi, Parastoo

AU - Devlin, Sean

AU - Giralt, Sergio A.

AU - Halton, Elizabeth

AU - Ruiz, Josel

AU - Maloy, Molly

AU - Mead, Elena

AU - Palomba, M. Lia

AU - Santomasso, Bianca

AU - Sauter, Craig S.

AU - Scordo, Michael

AU - Shah, Gunjan L.

AU - Perales, Miguel Angel

PY - 2021/3

Y1 - 2021/3

N2 - CD19-targeted chimeric antigen receptor (CAR) T cells have shown excellent activity against relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). CAR T cell therapy is associated with early toxicities, including cytokine release syndrome and neurotoxicity. The incidence and severity of these toxicities has been associated in part with baseline disease and patient characteristics, which also may impact overall survival (OS) and progression-free survival (PFS). However, there are limited data on patient selection and how to better predict toxicities or outcomes. Indexes used in patients with DLBCL, such as the International Prognostic Index (IPI and age-adjusted IPI [aaIPI]) and in transplantation recipients, such as the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), have not been evaluated in this setting. Here we evaluated 4 indices— IPI, aaIPI, HCT-CI, and the Charlson Comorbidity Index (CCI)—and their associations with early CAR T cell related-toxicities and outcomes. We demonstrated an association between high-risk IPI or aaIPI and inferior PFS in patients with R/R DLBCL treated with CAR T cell therapy. We also found an association between aaIPI and IPI with OS and neurotoxicity, respectively. CCI was not associated with toxicities or outcomes, and owing to the small sample size, we could not draw a conclusion regarding associations with the HCT-CI. Both the IPI and aaIPI are widely used tools that can now provide better information to guide selection of patients who would best benefit from CD19 CAR T cell therapy.

AB - CD19-targeted chimeric antigen receptor (CAR) T cells have shown excellent activity against relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL). CAR T cell therapy is associated with early toxicities, including cytokine release syndrome and neurotoxicity. The incidence and severity of these toxicities has been associated in part with baseline disease and patient characteristics, which also may impact overall survival (OS) and progression-free survival (PFS). However, there are limited data on patient selection and how to better predict toxicities or outcomes. Indexes used in patients with DLBCL, such as the International Prognostic Index (IPI and age-adjusted IPI [aaIPI]) and in transplantation recipients, such as the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), have not been evaluated in this setting. Here we evaluated 4 indices— IPI, aaIPI, HCT-CI, and the Charlson Comorbidity Index (CCI)—and their associations with early CAR T cell related-toxicities and outcomes. We demonstrated an association between high-risk IPI or aaIPI and inferior PFS in patients with R/R DLBCL treated with CAR T cell therapy. We also found an association between aaIPI and IPI with OS and neurotoxicity, respectively. CCI was not associated with toxicities or outcomes, and owing to the small sample size, we could not draw a conclusion regarding associations with the HCT-CI. Both the IPI and aaIPI are widely used tools that can now provide better information to guide selection of patients who would best benefit from CD19 CAR T cell therapy.

KW - Cellular therapy

KW - Chimeric antigen receptor T cells

KW - International Prognostic Index

KW - Non-Hodgkin lymphoma

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DO - 10.1016/j.jtct.2020.10.022

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AN - SCOPUS:85101145531

SN - 2666-6375

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SP - 233

EP - 240

JO - Transplantation and Cellular Therapy

JF - Transplantation and Cellular Therapy

IS - 3

ER -

The International Prognostic Index Is Associated with Outcomes in Diffuse Large B Cell Lymphoma after Chimeric Antigen Receptor T Cell Therapy

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Keywords

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