Cargando…

Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma

PURPOSE: New therapies are needed for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase 1b, open-label trial evaluated two anti-CD20-based triplet combinations. METHODS: Patients with R/R follicular lymphoma (FL; n = 13) were treated with obinutuzumab, atezolizumab, and polatuzumab v...

Descripción completa

Detalles Bibliográficos
Autores principales: Topp, Max S., Eradat, Herbert, Florschütz, Axel, Hochhaus, Andreas, Wrobel, Tomasz, Walewski, Jan, Knopinska-Posluszny, Wanda, Kanate, Abraham S., Lech-Maranda, Ewa, Brunnberg, Uta, Chitra, Surya, Nielsen, Tina G., Sellam, Gila, Shivhare, Mahesh, Lossos, Izidore S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931830/
https://www.ncbi.nlm.nih.gov/pubmed/35182224
http://dx.doi.org/10.1007/s00432-021-03847-5
_version_ 1784889319873314816
author Topp, Max S.
Eradat, Herbert
Florschütz, Axel
Hochhaus, Andreas
Wrobel, Tomasz
Walewski, Jan
Knopinska-Posluszny, Wanda
Kanate, Abraham S.
Lech-Maranda, Ewa
Brunnberg, Uta
Chitra, Surya
Nielsen, Tina G.
Sellam, Gila
Shivhare, Mahesh
Lossos, Izidore S.
author_facet Topp, Max S.
Eradat, Herbert
Florschütz, Axel
Hochhaus, Andreas
Wrobel, Tomasz
Walewski, Jan
Knopinska-Posluszny, Wanda
Kanate, Abraham S.
Lech-Maranda, Ewa
Brunnberg, Uta
Chitra, Surya
Nielsen, Tina G.
Sellam, Gila
Shivhare, Mahesh
Lossos, Izidore S.
author_sort Topp, Max S.
collection PubMed
description PURPOSE: New therapies are needed for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase 1b, open-label trial evaluated two anti-CD20-based triplet combinations. METHODS: Patients with R/R follicular lymphoma (FL; n = 13) were treated with obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola; 1.4 mg/kg/1.8 mg/kg) and patients with R/R diffuse large B-cell lymphoma (DLBCL; n = 23) received rituximab (R)-atezo-pola. The primary efficacy endpoint was complete response (CR) at end of induction (EOI) by PET-CT (investigator assessed; modified Lugano 2014 criteria). Safety endpoints were also assessed. RESULTS: 13 FL patients were treated and evaluable for safety; 2/23 DLBCL patients did not receive treatment and were not included in the safety population. Median observation time was 23.3 and 5.7 months in the FL and DLBCL cohorts, respectively. At EOI, CR rates in FL patients treated with G-atezo-pola at pola doses of 1.4 mg/kg (N = 3) and 1.8 mg/kg (N = 7) were 33% and 14%, respectively. In DLBCL patients receiving R-atezo-pola, the CR rate at EOI was 13%. In the FL cohort, 62% of patients experienced a grade 3–5 adverse event (AE; including two deaths) and 31% developed a serious AE (SAE). In DLBCL patients, R-atezo-pola was associated with a lower incidence of grade 3–5 AEs (24%; one death) and SAEs (10%). In both cohorts, the most common grade 3–5 AEs were hematologic toxicities. CONCLUSION: Based on these safety issues, considered as related specifically to G-atezo-pola, and limited efficacy, no further development of either combination is planned. TRIAL REGISTRATION: NCT02729896; Date of registration: April 6, 2016. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-021-03847-5.
format Online
Article
Text
id pubmed-9931830
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-99318302023-02-17 Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma Topp, Max S. Eradat, Herbert Florschütz, Axel Hochhaus, Andreas Wrobel, Tomasz Walewski, Jan Knopinska-Posluszny, Wanda Kanate, Abraham S. Lech-Maranda, Ewa Brunnberg, Uta Chitra, Surya Nielsen, Tina G. Sellam, Gila Shivhare, Mahesh Lossos, Izidore S. J Cancer Res Clin Oncol Original Article – Clinical Oncology PURPOSE: New therapies are needed for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase 1b, open-label trial evaluated two anti-CD20-based triplet combinations. METHODS: Patients with R/R follicular lymphoma (FL; n = 13) were treated with obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola; 1.4 mg/kg/1.8 mg/kg) and patients with R/R diffuse large B-cell lymphoma (DLBCL; n = 23) received rituximab (R)-atezo-pola. The primary efficacy endpoint was complete response (CR) at end of induction (EOI) by PET-CT (investigator assessed; modified Lugano 2014 criteria). Safety endpoints were also assessed. RESULTS: 13 FL patients were treated and evaluable for safety; 2/23 DLBCL patients did not receive treatment and were not included in the safety population. Median observation time was 23.3 and 5.7 months in the FL and DLBCL cohorts, respectively. At EOI, CR rates in FL patients treated with G-atezo-pola at pola doses of 1.4 mg/kg (N = 3) and 1.8 mg/kg (N = 7) were 33% and 14%, respectively. In DLBCL patients receiving R-atezo-pola, the CR rate at EOI was 13%. In the FL cohort, 62% of patients experienced a grade 3–5 adverse event (AE; including two deaths) and 31% developed a serious AE (SAE). In DLBCL patients, R-atezo-pola was associated with a lower incidence of grade 3–5 AEs (24%; one death) and SAEs (10%). In both cohorts, the most common grade 3–5 AEs were hematologic toxicities. CONCLUSION: Based on these safety issues, considered as related specifically to G-atezo-pola, and limited efficacy, no further development of either combination is planned. TRIAL REGISTRATION: NCT02729896; Date of registration: April 6, 2016. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-021-03847-5. Springer Berlin Heidelberg 2022-02-18 2023 /pmc/articles/PMC9931830/ /pubmed/35182224 http://dx.doi.org/10.1007/s00432-021-03847-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article – Clinical Oncology
Topp, Max S.
Eradat, Herbert
Florschütz, Axel
Hochhaus, Andreas
Wrobel, Tomasz
Walewski, Jan
Knopinska-Posluszny, Wanda
Kanate, Abraham S.
Lech-Maranda, Ewa
Brunnberg, Uta
Chitra, Surya
Nielsen, Tina G.
Sellam, Gila
Shivhare, Mahesh
Lossos, Izidore S.
Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
title Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
title_full Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
title_fullStr Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
title_full_unstemmed Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
title_short Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
title_sort anti-cd20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large b-cell lymphoma
topic Original Article – Clinical Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931830/
https://www.ncbi.nlm.nih.gov/pubmed/35182224
http://dx.doi.org/10.1007/s00432-021-03847-5
work_keys_str_mv AT toppmaxs anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT eradatherbert anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT florschutzaxel anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT hochhausandreas anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT wrobeltomasz anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT walewskijan anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT knopinskaposlusznywanda anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT kanateabrahams anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT lechmarandaewa anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT brunnberguta anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT chitrasurya anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT nielsentinag anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT sellamgila anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT shivharemahesh anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma
AT lossosizidores anticd20atezolizumabpolatuzumabvedotininrelapsedrefractoryfollicularanddiffuselargebcelllymphoma