{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:35:28Z","timestamp":1777890928513,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The dose of bendamustine used to treat previously untreated follicular lymphoma (FL) is sometimes reduced based on various clinical considerations, but the impact of such dose reductions on outcomes is unclear. We retrospectively analyzed 92 untreated FL patients treated with bendamustine at seven institutions in Japan. Dose reduction was defined as receiving less than 90% of the planned total dose of 1080\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over six cycles. Patients with disease progression observed at \u2264\u2009180\u2009days of treatment initiation were defined as primary bendamustine\u2010refractory (PBR). The 3\u2010year overall survival (OS) and progression\u2010free survival (PFS) were 87.1% and 71.8%, respectively. Seven patients were classified as PBR, six of whom received bendamustine at full dose without dose reduction, and they had significantly worse OS with 3\u2010year OS of 38.1%. We excluded the PBR cases from subsequent analyses of the dose intensity's prognostic significance. The dose\u2010reduction group had a significantly lower CR rate (93.0% vs. 74.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032). Similarly, the 3\u2010year PFS was significantly worse in the dose\u2010reduction group (86.8% vs. 68.1%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005). In univariate and multivariate analyses, dose reduction was associated with inferior PFS. In an analysis limited to patients who completed all six courses, the CR rate was comparable between the two groups, but 3\u2010year PFS was significantly worse in the dose\u2010reduction group (86.8% vs. 68.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041). Furthermore, even among patients who achieved CR, the 3\u2010year PFS tended to be poorer in the dose\u2010reduction group (85.7% vs. 72.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.062). These findings suggest that PBR cases are resistant to bendamustine itself regardless of the dose intensity. In contrast, among responders including those who achieved CR, dose reduction was associated with poorer PFS, indicating that maintaining treatment intensity is important for improving prognosis in the treatment of bendamustine\u2010responsive FL patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71702","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:25:47Z","timestamp":1772997947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced\u2010Dose Bendamustine as a First\u2010Line Treatment of Follicular Lymphoma Is Associated With Poorer Prognosis"],"prefix":"10.1002","volume":"15","author":[{"given":"Keisuke","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Hematology Institute of Science Tokyo Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7524-9339","authenticated-orcid":false,"given":"Atsushi","family":"Takahata","sequence":"additional","affiliation":[{"name":"Department of Hematology Yokosuka Kyosai Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuma","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology Japanese Red Cross Musashino Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keigo","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Hematology Ome Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Hematology Yokohama City Minato Red Cross Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Mukae","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Teishin Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Osada","sequence":"additional","affiliation":[{"name":"Department of Hematology The Fraternity Memorial Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hematology The Fraternity Memorial Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Mizuchi","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Teishin Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koh","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Yokohama City Minato Red Cross Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Department of Hematology Ome Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaku","family":"Oshikawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Japanese Red Cross Musashino Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiko","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Hematology Institute of Science Tokyo Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Toyota","sequence":"additional","affiliation":[{"name":"Department of Hematology Yokosuka Kyosai Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahide","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Institute of Science Tokyo Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Cancer Statistics \u201cCancer Information Service National Cancer Center Japan \u2010 National Cancer Registry Ministry of Health Labour and Welfare \u201d."},{"key":"e_1_2_12_3_1","unstructured":"National Comprehensive Cancer Network \u201cNCCN Clinical Practice Guidelines in Oncology: B\u2010Cell Lymphomas. 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