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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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 |
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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 |
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