{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:31:46Z","timestamp":1790015506299,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T00:00:00Z","timestamp":1292284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>In vitro studies in mantle cell lymphoma (MCL) cell lines and patient\u2010derived cells have demonstrated synergistic apoptosis with combined rituximab and bortezomib (R\u2010bortezomib) compared with single\u2010agent bortezomib. Therefore, the authors of this report evaluated R\u2010bortezomib in a preclinical model and in a phase 2 clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>A Hu\u2010MCL\u2010severe combined immunodeficiency (SCID) model engrafted with the Jeko cell line was treated with R\u2010bortezomib, bortezomib, or rituximab. Twenty\u2010five patients with relapsed follicular lymphoma (n = 11) and MCL (n = 14) received 375 mg\/m<jats:sup>2<\/jats:sup> rituximab on Days 1 and 8 and 1.3 to 1.5 mg\/m<jats:sup>2<\/jats:sup> bortezomib on Days 1, 4, 8, and 11 every 21 days for a median of 3 cycles (range, 1\u20105 cycles).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>R\u2010bortezomib resulted in a statistically significant improvement in overall survival in Hu\u2010MCL\u2010SCID mice. In the clinical trial, the overall response rate was 40% in all 25 patients, 55% in patients with follicular lymphoma, and 29% in patients with MCL. The estimated 2\u2010year progression\u2010free survival (PFS) rate was 24% (95% confidence interval [CI], 10%\u201053%) in all patients and 60% (95% CI, 20%\u201085%) in responding patients. Thirteen patients (52%) developed grade 3 neurotoxicity, which consisted of constipation\/ileus, sensory or motor neuropathy, or orthostatic hypotension. Patients who were heterozygous for the CD32a (Fc\u03b3 receptor IIa) 131 histidine (H) to arginine (R) polymorphism had a significantly decreased PFS (<jats:italic>P<\/jats:italic> = .009) after R\u2010bortezomib compared with HH and RR homozygotes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>R\u2010bortezomib had significant activity in patients with relapsed or refractory follicular lymphoma and MCL, although an unexpectedly high incidence of grade 3 neurologic toxicity was a potential limiting factor with this combination. Cancer 2011. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25792","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T10:25:09Z","timestamp":1292322309000},"page":"2442-2451","source":"Crossref","is-referenced-by-count":46,"title":["Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma"],"prefix":"10.1002","volume":"117","author":[{"given":"Robert A.","family":"Baiocchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lapo","family":"Alinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Lustberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Porcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie A.","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,14]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.108"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.01.133"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.050"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.6789"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn656"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.02.106"},{"key":"e_1_2_6_8_2","first-page":"2505","article-title":"A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies","volume":"8","author":"Aghajanian C","year":"2002","journal-title":"Clin Cancer Res."},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.1.1.7472"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404959"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1254"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2484"},{"key":"e_1_2_6_13_2","volume-title":"World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of the Hematopoeitic and Lymphoid Tissues. 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