{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:07:42Z","timestamp":1788444462935,"version":"build-2803163510"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"11","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,4,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 12 Spanish GELTAMO sites (ClinicalTrials.gov identifier: NCT02682641 ). Previously untreated MCL patients with indolent clinical forms defined by the following criteria were eligible: no disease-related symptoms, nonblastoid variants, Ki-67 &lt; 30%, and largest tumor diameter \u2264 3 cm. Both leukemic non-nodal and nodal subtypes were recruited. Patients received ibrutinib 560 mg once daily and a total of eight doses of rituximab 375 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . Ibrutinib could be discontinued after 2 years in the case of sustained undetectable minimal residual disease (MRD). The primary end point was the complete response (CR) rate achieved after 12 cycles according to Lugano criteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Fifty patients with MCL (male 66%; median age 65 years) were enrolled. After 12 cycles of treatment, 42 (84%; 95% CI, 74 to 94) patients had an overall response, including 40 (80%; 95% CI, 69 to 91) with CR. Moreover, undetectable MRD in peripheral blood was achieved in 87% (95% CI, 77 to 97) of cases. At 2 years, 24 of 35 evaluable patients (69%) could discontinue ibrutinib because of undetectable MRD. Four patients had disease progression; three were non-nodal MCL and carried high genomic complexity and TP53 mutations at enrollment. No unexpected toxicity was seen except one patient with severe aplastic anemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Frontline IR combination achieves a high rate of CRs and undetectable MRD in indolent clinical forms of MCL. Discontinuation seems appropriate in cases with undetectable MRD, except for TP53-mutated cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.02321","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T15:59:18Z","timestamp":1642175958000},"page":"1196-1205","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":62,"title":["Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0532-1204","authenticated-orcid":false,"given":"Eva","family":"Gin\u00e9","sequence":"first","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednic of Barcelona, Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red, C\u00e1ncer (CIBERONC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"de la Cruz","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Jim\u00e9nez Ubieto","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-3002","authenticated-orcid":false,"given":"Javier","family":"L\u00f3pez Jimenez","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-1028","authenticated-orcid":false,"given":"Alejandro","family":"Mart\u00edn Garc\u00eda-Sancho","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red, C\u00e1ncer (CIBERONC), Madrid, Spain"},{"name":"Hematology Department, Hospital Cl\u00ednico Universitario Salamanca, Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Jos\u00e9","family":"Terol","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednico de Valencia, Valencia, Spain"},{"name":"Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria (INCLIVA), Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Gonz\u00e1lez Barca","sequence":"additional","affiliation":[{"name":"Hematology Department, Institut Catal\u00e0 d\u2019Oncologia, Hospital Duran i Reynals, Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Casanova","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Costa del Sol Marbella, Marbella, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Hematology Department, MD Anderson Cancer Center, Madrid, 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