Giné, Evade la Cruz, FátimaJiménez Ubieto, AnaLópez Jimenez, JavierMartín García-Sancho, AlejandroTerol, M JoséGonzález Barca, EvaCasanova, Maríade la Fuente, AdolfoMarín-Niebla, AnaMuntañola, AnaGonzález-López, Tomás JoséAymerich, MartaSetoain, XavierCortés-Romera, MontserratRotger, AmandaRodríguez, SoniaMedina Herrera, AlejandroGarcía Sanz, RamónNadeu, FerranBeà, SilviaCampo, ElíasLópez-Guillermo, Armando2023-05-032023-05-032022-01-14http://hdl.handle.net/10668/20388The 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. 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 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. 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/AdenineAdultAgedAntineoplastic Combined Chemotherapy ProtocolsHumansLymphoma, Mantle-CellMaleNeoplasm, ResidualPiperidinesRituximabresearch article35030036open access10.1200/JCO.21.023211527-7755PMC8987223https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.02321https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987223/pdf