{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:12:30Z","timestamp":1783793550496,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5T32CA009666\u201027"],"award-info":[{"award-number":["5T32CA009666\u201027"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA16672"],"award-info":[{"award-number":["CA16672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non\u2010Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20\u00a0years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity\u2014rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors conducted an open\u2010label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression\u2010free survival (PFS) at 24 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study included 48 participants with previously untreated FL grade 1\u20133a (<jats:italic>N<\/jats:italic>\u00a0=\u00a038), or MZL (<jats:italic>N<\/jats:italic>\u00a0=\u00a010). Participants received 12, 28\u2010day cycles of lenalidomide (15\u00a0mg, days 1\u201321 cycle 1; 20\u00a0mg, cycles 2\u201312), rituximab (375\u00a0mg\/m<jats:sup>2<\/jats:sup> weekly in cycle 1; day 1 cycles 2\u201012), and ibrutinib 560\u00a0mg daily. With a median follow\u2010up of 65.3\u00a0months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%\u201391.4%) and 60\u2010month PFS was 59.7% (95% CI, 46.6%\u201376.4%). One death occurred unrelated to disease progression. Grade 3\u20134 adverse events were observed in 64.6%, including 50% with grade 3\u20134 rash.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3\u20134 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257).<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35114","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T17:41:57Z","timestamp":1700588517000},"page":"876-885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety and efficacy of ibrutinib in combination with rituximab and lenalidomide in previously untreated follicular and marginal zone lymphoma: An open label, phase 2 study"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3940-4451","authenticated-orcid":false,"given":"Max J.","family":"Gordon","sequence":"first","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Strati","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hun Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick B.","family":"Hagemeister","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Westin","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Samaniego","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-2096","authenticated-orcid":false,"given":"Mario L.","family":"Marques\u2010Piubelli","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Vega Vazquez","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin R.","family":"Parra Cuentas","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa M.","family":"Solis\u2010Soto","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Claret","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Averill","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Ibanez","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Fayad","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-3990","authenticated-orcid":false,"given":"Christopher R.","family":"Flowers","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Eric","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sattva S.","family":"Neelapu","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan H.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta J.","family":"Nastoupil","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102003\u201012\u20104434"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.21.3991"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa041869"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.1997.15.3.1110"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.18.1495"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(12)61763\u20102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2007.13.5376"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(10)62175\u20107"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102013\u201011\u2010531327"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.4.12.1963"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.05.024"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12708"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244851"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244917"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.03.039"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201007\u20104405"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102009\u201004\u2010217687"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102141.2007.06841.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21468"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.95"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(14)70455\u20103"},{"issue":"1","key":"e_1_2_9_23_1","article-title":"CALGB 50803 (Alliance): a phase 2 trial of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma","volume":"31","author":"Martin P","year":"2013","journal-title":"12\u2010ICML Hematol Oncol"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1805104"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1509388"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003121"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2201817"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102016\u201006\u2010718106"},{"key":"e_1_2_9_29_1","first-page":"253","volume-title":"Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels","author":"The Criteria Committee of the New York Heart Association","year":"1994"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.54.8800"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.274258"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(15)00169\u20102"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201014\u20103253"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.165415"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010019\u20100246\u20100"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.18.02365"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14201"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010021\u201001201\u20109"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201009\u2010804641"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00843"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa041869"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007104"}],"updated-by":[{"DOI":"10.1002\/cncr.35933","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000}}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.35114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:47:35Z","timestamp":1760276855000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.35114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,3,15]]}},"alternative-id":["10.1002\/cncr.35114"],"URL":"https:\/\/doi.org\/10.1002\/cncr.35114","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1002\/cncr.35933","asserted-by":"object"}]},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]},"assertion":[{"value":"2023-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}