{"entity":{"id":"paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025","kind":"paper","name":"Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial","aka":["ENRICH","Lewis 2025"],"tldr":"The first trial to show that a chemotherapy-free first-line combination beats immunochemotherapy in older people with mantle cell lymphoma.","summary":"A randomised, open-label, phase 2/3 superiority trial at 66 sites in the United Kingdom, Sweden, Norway, Finland and Denmark. Patients aged 60 or over with untreated mantle-cell lymphoma, Ann Arbor stage II to IV and performance status 0 to 2, were randomised 1 to 1, stratified by the investigator's pre-chosen immunochemotherapy, between that immunochemotherapy with rituximab and ibrutinib 560 mg daily with six to eight cycles of rituximab on the matched schedule. All responders received rituximab maintenance every eight weeks for two years; the ibrutinib group continued ibrutinib until progression or unacceptable toxicity. The trial was registered with EudraCT as 2015-000832-13.\n\nBetween 15 February 2016 and 30 June 2021, 397 patients were randomised, 198 to control and 199 to intervention; 107 (27 per cent) were pre-allocated to R-CHOP and 290 (73 per cent) to rituximab-bendamustine. Median age was 74 in both groups, and 296 patients (75 per cent) were male. At a median follow-up of 47.9 months the adjusted hazard ratio for progression-free survival was 0.69 (95 per cent confidence interval 0.52 to 0.90, p = 0.0034). Grade 3 or above adverse events were reported by 67 per cent of the ibrutinib-rituximab group and 70 per cent of the immunochemotherapy group.","asOf":"2026-10-01","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(25)01432-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41052510/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41052510"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","chemotherapy"],"technologies":[],"targets":["btk","cd20","ccnd1"],"drugs":["ibrutinib","rituximab","bendamustine","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":["cruk"],"pathways":["bcr-signalling"],"terms":["r-chop","maintenance-therapy"],"trials":["enrich","shine"],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol","b-trial-diversity"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2025,"doi":"10.1016/S0140-6736(25)01432-1","pmid":"41052510","authors":"Lewis DJ, Jerkeman M, Sorrell L, et al.","paperType":"rct","findings":["The adjusted hazard ratio for progression-free survival with ibrutinib-rituximab against immunochemotherapy was 0.69 (95 per cent confidence interval 0.52 to 0.90, p = 0.0034).","Against the pre-randomisation choice of R-CHOP the hazard ratio was 0.37 (0.22 to 0.62); against bendamustine-rituximab it was 0.91 (0.66 to 1.25).","Grade 3 or above adverse events were reported by 67 per cent of the ibrutinib-rituximab group and 70 per cent of the immunochemotherapy group.","Median age was 74 years in both groups; 296 patients (75 per cent) were male and 101 (25 per cent) female, and ethnicity data were not collected.","The trial was registered with EudraCT (2015-000832-13) and has no ClinicalTrials.gov record."],"whatItMeans":"The authors' conclusion is that ibrutinib-rituximab should be considered a new standard-of-care option for first-line treatment of older patients with mantle-cell lymphoma. The subgroup split means it is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab.","caveats":["Open-label, with progression-free survival assessed by investigators.","The overall superiority result is driven by the R-CHOP stratum, which was only 27 per cent of the trial; against the more commonly used bendamustine-rituximab the confidence interval crosses 1.","Ethnicity data were not collected, and three-quarters of participants were male, which reflects the disease but limits what can be said about other groups.","No overall survival result is reported at this analysis."],"changedPractice":true,"participants":397},"route":"/key-papers/paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025/","neighbours":{"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"ccnd1","kind":"target","name":"CCND1","route":"/targets/ccnd1/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"bendamustine","kind":"drug","name":"Bendamustine","route":"/drugs/bendamustine/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"institution":[{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"}],"term":[{"id":"maintenance-therapy","kind":"term","name":"Maintenance therapy","route":"/terms/maintenance-therapy/"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","route":"/terms/r-chop/"}],"trial":[{"id":"enrich","kind":"trial","name":"ENRICH","route":"/trials/enrich/"},{"id":"shine","kind":"trial","name":"SHINE","route":"/trials/shine/"}],"bottleneck":[{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-trial-diversity","kind":"bottleneck","name":"Trials do not represent the people who get cancer","route":"/bottlenecks/b-trial-diversity/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}],"idea":[{"id":"lymphoma-ev-fixed-duration-chemotherapy-free-first-line","kind":"idea","name":"Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas","route":"/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/"}],"paper":[{"id":"paper-triangle-ibrutinib-mantle-cell-lymphoma-dreyling-lancet-2024","kind":"paper","name":"TRIANGLE: ibrutinib with immunochemotherapy with or without autologous transplant versus immunochemotherapy and transplant in untreated mantle cell lymphoma","route":"/key-papers/paper-triangle-ibrutinib-mantle-cell-lymphoma-dreyling-lancet-2024/"}]}}