PMID- 33942442
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20210714
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 112
IP  - 7
DP  - 2021 Jul
TI  - A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in 
      relapsed/refractory diffuse large B-cell lymphoma.
PG  - 2845-2854
LID - 10.1111/cas.14937 [doi]
AB  - 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.
CI  - (c) 2021 Chugai Pharmaceutical Co., Ltd. Cancer Science published by John Wiley & 
      Sons Australia, Ltd on behalf of Japanese Cancer Association.
FAU - Terui, Yasuhito
AU  - Terui Y
AD  - Department of Hematology and Oncology, The Cancer Institute Hospital of the 
      Japanese Foundation for Cancer Research, Tokyo, Japan.
FAU - Rai, Shinya
AU  - Rai S
AUID- ORCID: 0000-0003-3929-9751
AD  - Department of Hematology and Rheumatology, Kindai University Hospital, Osaka, 
      Japan.
FAU - Izutsu, Koji
AU  - Izutsu K
AUID- ORCID: 0000-0001-9129-8057
AD  - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Yamaguchi, Motoko
AU  - Yamaguchi M
AD  - Department of Hematology and Oncology, Mie University Graduate School of 
      Medicine, Mie, Japan.
FAU - Takizawa, Jun
AU  - Takizawa J
AD  - Department of Hematology, Endocrinology and Metabolism, Faculty of Medicine, 
      Niigata University, Niigata, Japan.
FAU - Kuroda, Junya
AU  - Kuroda J
AD  - Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, 
      Kyoto, Japan.
FAU - Ishikawa, Takayuki
AU  - Ishikawa T
AD  - Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
FAU - Kato, Koji
AU  - Kato K
AUID- ORCID: 0000-0002-5815-4585
AD  - Department of Medicine and Biosystemic Science, Kyushu University Graduate School 
      of Medical Sciences, Fukuoka, Japan.
FAU - Suehiro, Youko
AU  - Suehiro Y
AD  - Department of Hematology, Kyushu Cancer Center, Fukuoka, Japan.
FAU - Fukuhara, Noriko
AU  - Fukuhara N
AD  - Department of Hematology and Rheumatology, Tohoku University Hospital, Miyagi, 
      Japan.
FAU - Ohmine, Ken
AU  - Ohmine K
AD  - Department of Hematology, Jichi Medical University Hospital, Tochigi, Japan.
FAU - Goto, Hideki
AU  - Goto H
AD  - Department of Hematology, Faculty of Medicine and Graduate School of Medicine, 
      Hokkaido University, Sapporo, Japan.
FAU - Yamamoto, Kazuhito
AU  - Yamamoto K
AD  - Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Aichi, 
      Japan.
FAU - Kanemura, Nobuhiro
AU  - Kanemura N
AD  - First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.
FAU - Ueda, Yasunori
AU  - Ueda Y
AD  - Department of Hematology, Kurashiki Central Hospital, Okayama, Japan.
FAU - Ishizawa, Kenichi
AU  - Ishizawa K
AD  - Department of Third Internal Medicine, Yamagata University Hospital, Yamagata, 
      Japan.
FAU - Kumagai, Kyoya
AU  - Kumagai K
AD  - Department of Hematology and Medical Oncology, Chiba Cancer Center, Chiba, Japan.
FAU - Kawasaki, Atsuko
AU  - Kawasaki A
AD  - Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
FAU - Saito, Tomohisa
AU  - Saito T
AD  - Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
FAU - Hashizume, Misato
AU  - Hashizume M
AD  - Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
FAU - Shibayama, Hirohiko
AU  - Shibayama H
AD  - Department of Hematology and Oncology, Osaka University Hospital, Osaka, Japan.
LA  - eng
GR  - Chugai Pharmaceutical Co., Ltd/
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210604
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoconjugates)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
RN  - KG6VO684Z6 (polatuzumab vedotin)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage/pharmacokinetics
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Bendamustine Hydrochloride/administration & dosage/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Granulocyte Colony-Stimulating Factor/administration & dosage
MH  - Humans
MH  - Immunoconjugates/administration & dosage/pharmacokinetics
MH  - Japan
MH  - Lymphoma, Large B-Cell, Diffuse/diagnostic imaging/*drug 
      therapy/mortality/pathology
MH  - Middle Aged
MH  - Positron Emission Tomography Computed Tomography
MH  - Progression-Free Survival
MH  - Rituximab/administration & dosage/pharmacokinetics
PMC - PMC8253277
OTO - NOTNLM
OT  - bendamustine
OT  - diffuse large B-cell lymphoma
OT  - polatuzumab vedotin
OT  - relapsed/refractory (R/R)
OT  - rituximab
COIS- This study was funded by Chugai Pharmaceutical Co., Ltd, Tokyo, Japan. YT 
      declares personal fees from Chugai, Celgene, BMS, Novartis, and Janssen, and 
      grant support from BMS, Takeda, Ono, and Eisai. SR declares personal fees from 
      Chugai. KI declares personal fees from Kyowa-Kirin and Eisai, and grant funding 
      from Celgene, Chugai, Novartis, Ono, Beyer, Daiichi-Sankyo, Takeda, Zenyaku, 
      Kyowa-Kirin, Eisai, AstraZeneca, Incyte, Abbvie, HUYA Japan, Sanofi, Symbio, 
      Solasia, Pfizer, Janssen, and Yakult. MY declares grant funding from Astellas, 
      Kyowa-Kirin, and Chugai. JT declares grant funding from Kyowa-Kirin and Ono. JK 
      declares personal fees from Celgene, Janssen, BMS, Ono, and Takeda, and grant 
      funding from Ono, Celgene, BMS, and Sysmex. TI declares grant funding from 
      Chugai, Novartis, Bayer, Eisai, Ono, Otsuka, Pfizer, Amgen, Daiichi-Sankyo, 
      Solasia, Celgene, and Takeda. KKa declares personal fees from Kyowa-Kirin, 
      Takeda, and MSD, and grant funding from Celgene, Daiichi-Sankyo, Novartis, and 
      Chugai. YS has no declarations. NF declares personal fees from Kyowa-Kirin and 
      Chugai, and grant funding from Abbvie, Incyte, Eisai, Ono, Gilead, Solasia, 
      Chugai, and Bayer. KO declares personal fees from Chugai, Celgene, BMS, Novartis, 
      Janssen, Ono, Kyowa-Kirin, CSL, and Eisai, and grant funding from Takara Bio. HG 
      has no declarations. KY declares personal fees from Chugai, Eisai, HUYA/IQVIA, 
      Mundi, and Takeda, and grant funding from Abbvie, AstraZeneca, Bayer, Celgene, 
      Chugai, Eisai, Incyte/IQVIA, Mundi, Nippon Shinyaku, Novartis, Solasia, Symbio, 
      and Zenyaku. NK has no declarations. YU has no declarations. KI declares personal 
      fees from Takeda, Ono, Chugai, Eisai, Novartis, and Celgene, and grant funding 
      from Symbio, Bayer, Abbvie, and Novartis. KKu has no declarations. AK, TS, and MH 
      are employees of Chugai. HS declares honoraria from Takeda, Novartis, Celgene, 
      Janssen, Chugai, and Kyowa-Kirin; research funding from Janssen, Ono, Celgene, 
      Novartis, Sanofi, AstraZeneca, AbbVie, and Chugai; and scholarship endowment from 
      Astellas, Teijin, Shionogi, Eisai, Sanofi, Taiho, and Nippon Shinyaku.
EDAT- 2021/05/05 06:00
MHDA- 2021/07/09 06:00
PMCR- 2021/07/01
CRDT- 2021/05/04 07:16
PHST- 2021/04/27 00:00 [revised]
PHST- 2021/01/14 00:00 [received]
PHST- 2021/04/28 00:00 [accepted]
PHST- 2021/05/05 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2021/05/04 07:16 [entrez]
PHST- 2021/07/01 00:00 [pmc-release]
AID - CAS14937 [pii]
AID - 10.1111/cas.14937 [doi]
PST - ppublish
SO  - Cancer Sci. 2021 Jul;112(7):2845-2854. doi: 10.1111/cas.14937. Epub 2021 Jun 4.