{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:37:39Z","timestamp":1777412259620,"version":"3.51.4"},"reference-count":44,"publisher":"American Association for Cancer Research (AACR)","issue":"20","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Purpose: We conducted a phase I study to determine the safety, maximum-tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies.<\/jats:p>\n                  <jats:p>Experimental Design: One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 \u03bcg\/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy.<\/jats:p>\n                  <jats:p>Results: Twenty-one patients with relapsed small lymphocytic lymphoma\/chronic lymphocytic leukemia (SLL\/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 \u03bcg\/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR\/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months).<\/jats:p>\n                  <jats:p>Conclusions: Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL\/CLL are warranted. Clin Cancer Res; 18(20); 5752\u201360. \u00a92012 AACR.<\/jats:p>","DOI":"10.1158\/1078-0432.ccr-12-0456","type":"journal-article","created":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T00:50:37Z","timestamp":1344991837000},"page":"5752-5760","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["A Phase I Dose-Finding Trial of Recombinant Interleukin-21 and Rituximab in Relapsed and Refractory Low Grade B-cell Lymphoproliferative Disorders"],"prefix":"10.1158","volume":"18","author":[{"given":"John M.","family":"Timmerman","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"David J.","family":"Andorsky","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"Reiko E.","family":"Yamada","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"Janet","family":"Kramer","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"Natarajan","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"Naomi","family":"Hunder","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington"}]},{"given":"John M.","family":"Pagel","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Division of Hematology & Oncology, University of California, Los Angeles, California; 2Division of Hematology, The Ohio State University, Columbus, Ohio; 3ZymoGenetics, Inc; and 4University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, 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