Cargando…

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma

Polatuzumab vedotin (pola) is a CD79b‐targeted antibody‐drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open‐label, single‐arm study of pola 1.8 mg/kg, bendamustine 90 mg/m(2), rituximab 375 mg/m(2) (pola + BR) Q3W for up to six cycles in patien...

Descripción completa

Detalles Bibliográficos
Autores principales: Terui, Yasuhito, Rai, Shinya, Izutsu, Koji, Yamaguchi, Motoko, Takizawa, Jun, Kuroda, Junya, Ishikawa, Takayuki, Kato, Koji, Suehiro, Youko, Fukuhara, Noriko, Ohmine, Ken, Goto, Hideki, Yamamoto, Kazuhito, Kanemura, Nobuhiro, Ueda, Yasunori, Ishizawa, Kenichi, Kumagai, Kyoya, Kawasaki, Atsuko, Saito, Tomohisa, Hashizume, Misato, Shibayama, Hirohiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253277/
https://www.ncbi.nlm.nih.gov/pubmed/33942442
http://dx.doi.org/10.1111/cas.14937
_version_ 1783717476126687232
author Terui, Yasuhito
Rai, Shinya
Izutsu, Koji
Yamaguchi, Motoko
Takizawa, Jun
Kuroda, Junya
Ishikawa, Takayuki
Kato, Koji
Suehiro, Youko
Fukuhara, Noriko
Ohmine, Ken
Goto, Hideki
Yamamoto, Kazuhito
Kanemura, Nobuhiro
Ueda, Yasunori
Ishizawa, Kenichi
Kumagai, Kyoya
Kawasaki, Atsuko
Saito, Tomohisa
Hashizume, Misato
Shibayama, Hirohiko
author_facet Terui, Yasuhito
Rai, Shinya
Izutsu, Koji
Yamaguchi, Motoko
Takizawa, Jun
Kuroda, Junya
Ishikawa, Takayuki
Kato, Koji
Suehiro, Youko
Fukuhara, Noriko
Ohmine, Ken
Goto, Hideki
Yamamoto, Kazuhito
Kanemura, Nobuhiro
Ueda, Yasunori
Ishizawa, Kenichi
Kumagai, Kyoya
Kawasaki, Atsuko
Saito, Tomohisa
Hashizume, Misato
Shibayama, Hirohiko
author_sort Terui, Yasuhito
collection PubMed
description Polatuzumab vedotin (pola) is a CD79b‐targeted antibody‐drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open‐label, single‐arm study of pola 1.8 mg/kg, bendamustine 90 mg/m(2), rituximab 375 mg/m(2) (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography–computed tomography (PET‐CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty‐five patients (median age 71 [range 46‐86] years) were enrolled. Twenty‐three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow‐up of 5.4 (0.7‐11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1‐52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression‐free survival was 5.2 months (95% CI 3.6‐not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3‐4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1‐2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI‐184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.
format Online
Article
Text
id pubmed-8253277
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-82532772021-07-13 A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma Terui, Yasuhito Rai, Shinya Izutsu, Koji Yamaguchi, Motoko Takizawa, Jun Kuroda, Junya Ishikawa, Takayuki Kato, Koji Suehiro, Youko Fukuhara, Noriko Ohmine, Ken Goto, Hideki Yamamoto, Kazuhito Kanemura, Nobuhiro Ueda, Yasunori Ishizawa, Kenichi Kumagai, Kyoya Kawasaki, Atsuko Saito, Tomohisa Hashizume, Misato Shibayama, Hirohiko Cancer Sci Original Articles Polatuzumab vedotin (pola) is a CD79b‐targeted antibody‐drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open‐label, single‐arm study of pola 1.8 mg/kg, bendamustine 90 mg/m(2), rituximab 375 mg/m(2) (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography–computed tomography (PET‐CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty‐five patients (median age 71 [range 46‐86] years) were enrolled. Twenty‐three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow‐up of 5.4 (0.7‐11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1‐52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression‐free survival was 5.2 months (95% CI 3.6‐not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3‐4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1‐2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI‐184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT. John Wiley and Sons Inc. 2021-06-04 2021-07 /pmc/articles/PMC8253277/ /pubmed/33942442 http://dx.doi.org/10.1111/cas.14937 Text en © 2021 Chugai Pharmaceutical Co., Ltd. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Terui, Yasuhito
Rai, Shinya
Izutsu, Koji
Yamaguchi, Motoko
Takizawa, Jun
Kuroda, Junya
Ishikawa, Takayuki
Kato, Koji
Suehiro, Youko
Fukuhara, Noriko
Ohmine, Ken
Goto, Hideki
Yamamoto, Kazuhito
Kanemura, Nobuhiro
Ueda, Yasunori
Ishizawa, Kenichi
Kumagai, Kyoya
Kawasaki, Atsuko
Saito, Tomohisa
Hashizume, Misato
Shibayama, Hirohiko
A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma
title A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma
title_full A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma
title_fullStr A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma
title_full_unstemmed A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma
title_short A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B‐cell lymphoma
title_sort phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large b‐cell lymphoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253277/
https://www.ncbi.nlm.nih.gov/pubmed/33942442
http://dx.doi.org/10.1111/cas.14937
work_keys_str_mv AT teruiyasuhito aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT raishinya aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT izutsukoji aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT yamaguchimotoko aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT takizawajun aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kurodajunya aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT ishikawatakayuki aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT katokoji aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT suehiroyouko aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT fukuharanoriko aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT ohmineken aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT gotohideki aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT yamamotokazuhito aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kanemuranobuhiro aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT uedayasunori aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT ishizawakenichi aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kumagaikyoya aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kawasakiatsuko aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT saitotomohisa aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT hashizumemisato aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT shibayamahirohiko aphase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT teruiyasuhito phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT raishinya phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT izutsukoji phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT yamaguchimotoko phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT takizawajun phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kurodajunya phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT ishikawatakayuki phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT katokoji phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT suehiroyouko phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT fukuharanoriko phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT ohmineken phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT gotohideki phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT yamamotokazuhito phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kanemuranobuhiro phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT uedayasunori phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT ishizawakenichi phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kumagaikyoya phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT kawasakiatsuko phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT saitotomohisa phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT hashizumemisato phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma
AT shibayamahirohiko phase2studyofpolatuzumabvedotinbendamustinerituximabinrelapsedrefractorydiffuselargebcelllymphoma