{"entity":{"id":"paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025","kind":"paper","name":"Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma","aka":["ECHO","Wang 2025","Acalabrutinib with bendamustine and rituximab"],"tldr":"Repeating the SHINE design with a more selective targeted tablet gave another seventeen months before relapse, and again did not extend life.","summary":"A randomised trial in patients aged 65 or over with previously untreated mantle cell lymphoma, designed to test whether acalabrutinib, more selective and better tolerated than ibrutinib, would do in this setting what ibrutinib had not. Patients received acalabrutinib 100 mg twice daily or placebo until progression or unacceptable toxicity, plus six cycles of bendamustine 90 mg per square metre on days 1 and 2 and rituximab 375 mg per square metre on day 1, followed by two years of rituximab maintenance in responders. Crossover to acalabrutinib at progression was permitted. The primary endpoint was progression-free survival by independent review committee.\n\n598 patients were randomised, 299 per arm. At a median follow-up of 49.8 months by the reverse Kaplan-Meier method, median progression-free survival was 66.4 months with acalabrutinib against 49.6 months with placebo (hazard ratio 0.73, 95 per cent confidence interval 0.57 to 0.94, p = 0.0160), with benefit across all subgroups including those with high-risk features. Overall response and complete response rates were 91.0 and 66.6 per cent with acalabrutinib against 88.0 and 53.5 per cent. Overall survival was not significantly different (hazard ratio 0.86, 0.65 to 1.13, p = 0.27). Grade 3 or greater adverse events occurred in 88.9 and 88.2 per cent.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2025","url":"https://doi.org/10.1200/JCO-25-00690"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40311141/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40311141"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","chemotherapy"],"technologies":[],"targets":["btk","cd20","ccnd1"],"drugs":["acalabrutinib","bendamustine","rituximab"],"companies":["astrazeneca"],"institutions":[],"pathways":["bcr-signalling"],"terms":[],"trials":["nct02972840","shine","enrich"],"people":["michael-wang","martin-dreyling"],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-25-00690","pmid":"40311141","authors":"Wang M, Salek D, Belada D, et al.","paperType":"rct","findings":["Median progression-free survival was 66.4 months with acalabrutinib against 49.6 months with placebo (hazard ratio 0.73, 95 per cent confidence interval 0.57 to 0.94, p = 0.0160).","Overall response and complete response rates were 91.0 and 66.6 per cent with acalabrutinib against 88.0 and 53.5 per cent with placebo.","Overall survival was not significantly different (hazard ratio 0.86, 0.65 to 1.13, p = 0.27).","Grade 3 or greater adverse events were reported in 88.9 per cent with acalabrutinib and 88.2 per cent with placebo.","Benefit was seen across all subgroups, including those with high-risk features."],"whatItMeans":"A second randomised confirmation that adding a Bruton tyrosine kinase inhibitor to first-line bendamustine-rituximab delays progression in older patients with mantle cell lymphoma, with a toxicity profile that did not improve as much as the drug's selectivity promised.","caveats":["No overall survival benefit, as in SHINE; crossover at progression was permitted, which makes a survival difference harder to detect.","Grade 3 or greater adverse events in roughly 89 per cent of both arms shows how much of the burden comes from the chemotherapy backbone rather than the inhibitor.","The trial recruited through the COVID-19 pandemic, which the investigators have discussed as affecting early mortality in both arms.","Indefinite acalabrutinib until progression, with the cost and adherence implications that carries."],"changedPractice":true,"participants":598},"route":"/key-papers/paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-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":"acalabrutinib","kind":"drug","name":"Acalabrutinib","route":"/drugs/acalabrutinib/"},{"id":"bendamustine","kind":"drug","name":"Bendamustine","route":"/drugs/bendamustine/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"}],"trial":[{"id":"nct02972840","kind":"trial","name":"A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL","route":"/trials/nct02972840/"},{"id":"enrich","kind":"trial","name":"ENRICH","route":"/trials/enrich/"},{"id":"shine","kind":"trial","name":"SHINE","route":"/trials/shine/"}],"person":[{"id":"martin-dreyling","kind":"person","name":"Martin Dreyling","route":"/people/martin-dreyling/"},{"id":"michael-wang","kind":"person","name":"Michael L. Wang","route":"/people/michael-wang/"}],"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/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"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/"}]}}