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Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas

The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dos...

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Autores principales: Lynch, Ryan C., Poh, Christina, Ujjani, Chaitra S., Warren, Edus H., Smith, Stephen D., Shadman, Mazyar, Morris, Karolyn, Lee, Sydney, Rasmussen, Heather, Ottemiller, Susan, Shelby, Megan, Keo, Sarith, Verni, Kaitlin, Kurtz, David M., Alizadeh, Ash A., Chabon, Jacob J., Hogan, Gregory J., Schulz, Andre, Gooley, Ted, Voutsinas, Jenna M., Gopal, Ajay K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241852/
https://www.ncbi.nlm.nih.gov/pubmed/36521030
http://dx.doi.org/10.1182/bloodadvances.2022009145
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author Lynch, Ryan C.
Poh, Christina
Ujjani, Chaitra S.
Warren, Edus H.
Smith, Stephen D.
Shadman, Mazyar
Morris, Karolyn
Lee, Sydney
Rasmussen, Heather
Ottemiller, Susan
Shelby, Megan
Keo, Sarith
Verni, Kaitlin
Kurtz, David M.
Alizadeh, Ash A.
Chabon, Jacob J.
Hogan, Gregory J.
Schulz, Andre
Gooley, Ted
Voutsinas, Jenna M.
Gopal, Ajay K.
author_facet Lynch, Ryan C.
Poh, Christina
Ujjani, Chaitra S.
Warren, Edus H.
Smith, Stephen D.
Shadman, Mazyar
Morris, Karolyn
Lee, Sydney
Rasmussen, Heather
Ottemiller, Susan
Shelby, Megan
Keo, Sarith
Verni, Kaitlin
Kurtz, David M.
Alizadeh, Ash A.
Chabon, Jacob J.
Hogan, Gregory J.
Schulz, Andre
Gooley, Ted
Voutsinas, Jenna M.
Gopal, Ajay K.
author_sort Lynch, Ryan C.
collection PubMed
description The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]–EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.
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spelling pubmed-102418522023-06-07 Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas Lynch, Ryan C. Poh, Christina Ujjani, Chaitra S. Warren, Edus H. Smith, Stephen D. Shadman, Mazyar Morris, Karolyn Lee, Sydney Rasmussen, Heather Ottemiller, Susan Shelby, Megan Keo, Sarith Verni, Kaitlin Kurtz, David M. Alizadeh, Ash A. Chabon, Jacob J. Hogan, Gregory J. Schulz, Andre Gooley, Ted Voutsinas, Jenna M. Gopal, Ajay K. Blood Adv Clinical Trials and Observations The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]–EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877. The American Society of Hematology 2022-12-19 /pmc/articles/PMC10241852/ /pubmed/36521030 http://dx.doi.org/10.1182/bloodadvances.2022009145 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Trials and Observations
Lynch, Ryan C.
Poh, Christina
Ujjani, Chaitra S.
Warren, Edus H.
Smith, Stephen D.
Shadman, Mazyar
Morris, Karolyn
Lee, Sydney
Rasmussen, Heather
Ottemiller, Susan
Shelby, Megan
Keo, Sarith
Verni, Kaitlin
Kurtz, David M.
Alizadeh, Ash A.
Chabon, Jacob J.
Hogan, Gregory J.
Schulz, Andre
Gooley, Ted
Voutsinas, Jenna M.
Gopal, Ajay K.
Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
title Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
title_full Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
title_fullStr Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
title_full_unstemmed Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
title_short Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas
title_sort polatuzumab vedotin with infusional chemotherapy for untreated aggressive b-cell non-hodgkin lymphomas
topic Clinical Trials and Observations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241852/
https://www.ncbi.nlm.nih.gov/pubmed/36521030
http://dx.doi.org/10.1182/bloodadvances.2022009145
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