{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:47:12Z","timestamp":1790423232830,"version":"4.1.0"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenstr\u00f6m's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P &lt; .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P &lt; .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P &lt; .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade \u2265 3 adverse events of clinical interest generally decreased over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.00838","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T17:57:14Z","timestamp":1633370234000},"page":"52-62","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":114,"title":["Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenstr\u00f6m's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9782-9012","authenticated-orcid":false,"given":"Christian","family":"Buske","sequence":"first","affiliation":[{"name":"Institute of Experimental Cancer Research, Comprehensive Cancer Center Ulm, University Hospital of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-4593","authenticated-orcid":false,"given":"Judith","family":"Trotman","sequence":"additional","affiliation":[{"name":"Concord Hospital, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-2787","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Garc\u00eda-Sanz","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital of Salamanca (HUS\/IBSAL), CIBERONC and Cancer Research Institute of Salamanca-IBMCC (USAL-CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-2733","authenticated-orcid":false,"given":"David","family":"MacDonald","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital, University of Ottawa, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Leblond","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019H\u00e9matologie H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re AP-HP, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Mahe","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Herbaux","sequence":"additional","affiliation":[{"name":"Centre Hospitalier R\u00e9gional Universitaire de Lille, Institute of Hematology-Transfusion, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey V.","family":"Matous","sequence":"additional","affiliation":[{"name":"Colorado Blood Cancer Institute, Denver, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9759-5017","authenticated-orcid":false,"given":"Constantine S.","family":"Tam","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre & St Vincent's Hospital and the University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard T.","family":"Heffner","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Varettoni","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-9156","authenticated-orcid":false,"given":"M. Lia","family":"Palomba","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim","family":"Shustik","sequence":"additional","affiliation":[{"name":"Royal Victoria Hospital at McGill University Health Centre, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-5832","authenticated-orcid":false,"given":"Efstathios","family":"Kastritis","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens School of Medicine, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6393-6154","authenticated-orcid":false,"given":"Steven P.","family":"Treon","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Ping","sequence":"additional","affiliation":[{"name":"Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Hauns","sequence":"additional","affiliation":[{"name":"Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Arango-Hisijara","sequence":"additional","affiliation":[{"name":"Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens School of Medicine, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","volume-title":"Imbruvica (ibrutinib) [prescribing information]","year":"2020"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802917"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30632-5"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.6426"},{"key":"b5","volume-title":"NCCN Clinical Practice Guidelines in Oncology. 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