{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:43:58Z","timestamp":1793641438762,"version":"4.5.1"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Rituximab, the first anti\u2010CD20 monoclonal antibody, has dramatically improved outcomes for patients with B\u2010cell lymphoproliferative disorders. Obinutuzumab was developed to potentiate activity and overcome resistance to rituximab. Clinical data suggest that obinutuzumab is superior to rituximab in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Yet, it has increased toxicity. This systematic review and meta\u2010analysis compiled all randomized controlled trials (RCTs) comparing obinutuzumab\u2010based regimens with rituximab\u2010based regimens to better assess their toxicity profile. Primary outcome was grade 3\u20134 infections; secondary outcomes included any adverse events (AE), grade 3\u20134 AE, drug discontinuation rate, and 3\u2010years mortality. Relative risks (RRs) were estimated and pooled using a fixed\u2010effect model, unless there was significant heterogeneity, in which case a random\u2010effects model was used. Our comprehensive search yielded five RCTs conducted between 2009 and 2014, including 4247 patients. The trials included FL patients, CLL and diffuse large B cell lymphoma. Monoclonal antibodies were given with different chemotherapy regimens (in four trials) or as monotherapy (in one trial). The point estimate favored increase in both grade 3\u20134 infections rate (RR 1.17 [95% CI, 1.0\u20131.36]) and any AE rate (RR 1.05 [95% 1\u20131.1]) with obinutuzumab, although this was not statistically significant. There was a significantly increased rate of grade 3\u20134 AE (RR 1.15 [95% CI, 1.09\u20131.2]), as well as grade 3\u20134 toxicities including thrombocytopenia (RR 2.8 [95% CI, 1.92\u20134.06]), infusion related reactions (RR 2.8 [95% CI, 2.16\u20103.64]) and cardiac events (RR 1.65 [95% CI, 1.11\u20102.46]). There was no significant difference in grade 3\u20134 anemia and neutropenia nor in the 3\u2010year mortality rate. The point estimate favored increase in discontinuation rate due to AE with obinutuzumab, although without statistical significance (RR 1.24 [95% CI, 1.0\u20131.54]). In conclusion, physicians need to weigh the clinical benefits of this agent against higher toxicity.<\/jats:p>","DOI":"10.1002\/hon.2828","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T06:33:42Z","timestamp":1606718022000},"page":"215-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Obinutuzumab\u2010related adverse events: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3387-5930","authenticated-orcid":false,"given":"Irina","family":"Amitai","sequence":"first","affiliation":[{"name":"Odette Cancer Center Sunnybrook Health Sciences Center  Toronto Ontario Canada"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Gafter\u2010Gvili","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"Institute of Hematology Davidoff Cancer Center Rabin Medical Center  Petah Tikva Israel"},{"name":"Department of Internal Medicine A Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-148X","authenticated-orcid":false,"given":"Liat","family":"Shargian\u2010Alon","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"Institute of Hematology Davidoff Cancer Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Raanani","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"Institute of Hematology Davidoff Cancer Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit","family":"Gurion","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"Institute of Hematology Davidoff Cancer Center Rabin Medical Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-632745"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-01-0016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.5376"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70235-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70002-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2011.02.009"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15232"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000303"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614598"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.14"},{"key":"e_1_2_7_12_1","unstructured":"GoedeV FischerK DyerM et\u00a0al.Overall survival benefit of obinutuzumab over rituximab when combined with chlorambucil in patients with chronic lymphocytic leukemia and comorbidities: final survival analysis of the Cll11 Study. Paper presented at: EHA 2018; EHA Library. Goede V. 15th June 2018;215923."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.3402"},{"key":"e_1_2_7_14_1","first-page":"190","article-title":"Obinutuzumab versus rituximab in combination with ACVBP\u201014 or CHOP\u201014 following a PET\u2010driven strategy in Aa\u2010IPI 1\u20133 DLBCL patients (<60 years): Third planned interim and final analyses of the GAINED trial","volume":"130","author":"Casasnovas RO","year":"2017","journal-title":"Blood"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2077"},{"key":"e_1_2_7_16_1","unstructured":"HigginsJPT GreenS eds.Cochrane handbook for systematic reviews of interventions: version 6.2019. The Cochrane Collaboration Available athttps:\/\/training.cochrane.org\/handbook\/current"},{"key":"e_1_2_7_17_1","unstructured":"US Department of Heath and Human Services. National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.2017.https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/CTCAE_v5_Quick_Reference_8.5x11.pdf"},{"key":"e_1_2_7_18_1","unstructured":"JulianH JamesT.Review Manager Version 5.2 for Windows. The Cochrane Collaboration Oxford UK."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.2139"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-670802"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2016.42"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.8960"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-517037"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03494.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0959-x"}],"container-title":["Hematological Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.2828","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hon.2828","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.2828","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T18:49:05Z","timestamp":1693594145000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hon.2828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,10]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/hon.2828"],"URL":"https:\/\/doi.org\/10.1002\/hon.2828","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/HON.2828\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2828\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2828\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2828\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2828\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2828\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/HON.2828\/v1\/review1","asserted-by":"object"}]},"ISSN":["0278-0232","1099-1069"],"issn-type":[{"value":"0278-0232","type":"print"},{"value":"1099-1069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,10]]},"assertion":[{"value":"2020-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}