Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers

Abstract Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop r...

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Main Authors: Timothy J. Voorhees, Eric M. McLaughlin, Pallawi Torka, Jorge Florindez, Na Hyun Kim, Tamara K. Moyo, Heather Reves, Nuttavut Sumransub, Saarang Deshpande, Ashley Rose, Cassandra Duarte, Muhammad Salman Faisal, Showkat Hamid, Suki Subbiah, Sabarish Ayyappan, Lauren Shea, Matt Cortese, Krish Patel, Ajay Major, Hayder Saeed, Jakub Svoboda, Sanjal Desai, Praveen Ramakrishnan Geethakumari, Mehdi Hamadani, Natalie Grover, Narendranath Epperla
Format: Article
Language:English
Published: Nature Publishing Group 2025-03-01
Series:Blood Cancer Journal
Online Access:https://doi.org/10.1038/s41408-025-01257-1
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author Timothy J. Voorhees
Eric M. McLaughlin
Pallawi Torka
Jorge Florindez
Na Hyun Kim
Tamara K. Moyo
Heather Reves
Nuttavut Sumransub
Saarang Deshpande
Ashley Rose
Cassandra Duarte
Muhammad Salman Faisal
Showkat Hamid
Suki Subbiah
Sabarish Ayyappan
Lauren Shea
Matt Cortese
Krish Patel
Ajay Major
Hayder Saeed
Jakub Svoboda
Sanjal Desai
Praveen Ramakrishnan Geethakumari
Mehdi Hamadani
Natalie Grover
Narendranath Epperla
author_facet Timothy J. Voorhees
Eric M. McLaughlin
Pallawi Torka
Jorge Florindez
Na Hyun Kim
Tamara K. Moyo
Heather Reves
Nuttavut Sumransub
Saarang Deshpande
Ashley Rose
Cassandra Duarte
Muhammad Salman Faisal
Showkat Hamid
Suki Subbiah
Sabarish Ayyappan
Lauren Shea
Matt Cortese
Krish Patel
Ajay Major
Hayder Saeed
Jakub Svoboda
Sanjal Desai
Praveen Ramakrishnan Geethakumari
Mehdi Hamadani
Natalie Grover
Narendranath Epperla
author_sort Timothy J. Voorhees
collection DOAJ
description Abstract Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop refractory disease or who become intolerant of BV and anti-PD-1 therapies (double refractory/intolerant; DR/INT). Here, we evaluated outcomes in patients with DR/INT cHL from 15 US academic medical centers. A total of 173 patients were identified as DR/INT. The median overall survival from the time of cHL diagnosis (OS-1) was 14.8 years (95% CI: 10.9–20.9 years) and the 10-year OS-1 estimate was 62% (95% CI: 52–70%). After accounting for differences in age, patients who underwent autologous stem cell transplant prior to developing DR/INT had significantly longer OS-1 (HR 0.53, 95% CI: 0.29–0.96, p = 0.04). Median OS from time of DR/INT (OS-2) was 7.4 years (95% CI: 4.3-NR) and the 5-year OS-2 estimate was 57% (95% CI: 48-66%). Both anti-PD-1 and BV based therapy rechallenge were effective with median PFS of 237 days (95% CI: 155-357 days) and 183 days (95% CI: 108–273 days), respectively. Finally, advanced therapy options such as CD30 directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after DR/INT were associated with improved OS-2 (p < 0.001). To our knowledge, this represents the largest cohort of patients with DR/INT cHL. OS-2 will serve as a benchmark for future studies aiming to improve survival in DR/INT cHL.
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spelling doaj-art-79391268a64a4ef288a78ebe8bdbcbf52025-08-20T03:40:44ZengNature Publishing GroupBlood Cancer Journal2044-53852025-03-011511710.1038/s41408-025-01257-1Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centersTimothy J. Voorhees0Eric M. McLaughlin1Pallawi Torka2Jorge Florindez3Na Hyun Kim4Tamara K. Moyo5Heather Reves6Nuttavut Sumransub7Saarang Deshpande8Ashley Rose9Cassandra Duarte10Muhammad Salman Faisal11Showkat Hamid12Suki Subbiah13Sabarish Ayyappan14Lauren Shea15Matt Cortese16Krish Patel17Ajay Major18Hayder Saeed19Jakub Svoboda20Sanjal Desai21Praveen Ramakrishnan Geethakumari22Mehdi Hamadani23Natalie Grover24Narendranath Epperla25Ohio State University, James Comprehensive Cancer CenterCenter for Biostatistics, The Ohio State UniversityMemorial Sloan Kettering Cancer CenterUniversity of North Carolina, Lineberger Comprehensive Cancer CenterMedical College of Wisconsin Cancer CenterAtrium Health, Levine Cancer InstituteHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical CenterUniversity of Minnesota, Masonic Cancer CenterUniversity of Pennsylvania, Abramson Cancer CenterMoffitt Cancer CenterUniversity of Colorado Cancer CenterRoswell Park Comprehensive Cancer CenterRoswell Park Comprehensive Cancer CenterLouisiana State University, Stanley S. Scott Cancer CenterUniversity of Iowa, Holden Comprehensive Cancer CenterUniversity of Alabama at Birmingham, O’Neal Comprehensive Cancer CenterRoswell Park Comprehensive Cancer CenterSwedish Cancer InstituteUniversity of Colorado Cancer CenterMoffitt Cancer CenterUniversity of Pennsylvania, Abramson Cancer CenterUniversity of Minnesota, Masonic Cancer CenterHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical CenterMedical College of Wisconsin Cancer CenterUniversity of North Carolina, Lineberger Comprehensive Cancer CenterOhio State University, James Comprehensive Cancer CenterAbstract Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop refractory disease or who become intolerant of BV and anti-PD-1 therapies (double refractory/intolerant; DR/INT). Here, we evaluated outcomes in patients with DR/INT cHL from 15 US academic medical centers. A total of 173 patients were identified as DR/INT. The median overall survival from the time of cHL diagnosis (OS-1) was 14.8 years (95% CI: 10.9–20.9 years) and the 10-year OS-1 estimate was 62% (95% CI: 52–70%). After accounting for differences in age, patients who underwent autologous stem cell transplant prior to developing DR/INT had significantly longer OS-1 (HR 0.53, 95% CI: 0.29–0.96, p = 0.04). Median OS from time of DR/INT (OS-2) was 7.4 years (95% CI: 4.3-NR) and the 5-year OS-2 estimate was 57% (95% CI: 48-66%). Both anti-PD-1 and BV based therapy rechallenge were effective with median PFS of 237 days (95% CI: 155-357 days) and 183 days (95% CI: 108–273 days), respectively. Finally, advanced therapy options such as CD30 directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after DR/INT were associated with improved OS-2 (p < 0.001). To our knowledge, this represents the largest cohort of patients with DR/INT cHL. OS-2 will serve as a benchmark for future studies aiming to improve survival in DR/INT cHL.https://doi.org/10.1038/s41408-025-01257-1
spellingShingle Timothy J. Voorhees
Eric M. McLaughlin
Pallawi Torka
Jorge Florindez
Na Hyun Kim
Tamara K. Moyo
Heather Reves
Nuttavut Sumransub
Saarang Deshpande
Ashley Rose
Cassandra Duarte
Muhammad Salman Faisal
Showkat Hamid
Suki Subbiah
Sabarish Ayyappan
Lauren Shea
Matt Cortese
Krish Patel
Ajay Major
Hayder Saeed
Jakub Svoboda
Sanjal Desai
Praveen Ramakrishnan Geethakumari
Mehdi Hamadani
Natalie Grover
Narendranath Epperla
Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers
Blood Cancer Journal
title Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers
title_full Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers
title_fullStr Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers
title_full_unstemmed Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers
title_short Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers
title_sort outcomes in patients with classic hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti pd 1 therapy a real world analysis from 15 u s academic centers
url https://doi.org/10.1038/s41408-025-01257-1
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