# ENRICH

Source: https://onco.cc/trials/enrich/  
OnCo record `enrich` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A British and Nordic trial took chemotherapy out of first-line treatment for older people with mantle cell lymphoma and found the two-drug, chemotherapy-free combination worked better.

## Summary

ENRICH is the first randomised trial in untreated mantle cell lymphoma to show that a chemotherapy-free first line beats immunochemotherapy. It ran at 66 sites in the United Kingdom, Sweden, Norway, Finland and Denmark, and randomised 397 patients aged 60 or over with stage II to IV disease and performance status 0 to 2 between ibrutinib 560 mg daily with rituximab, and rituximab with the investigator's pre-chosen chemotherapy, either R-CHOP or bendamustine. All responders received two years of rituximab maintenance every eight weeks; the ibrutinib group continued ibrutinib until progression.

At a median follow-up of 47.9 months, progression-free survival favoured ibrutinib-rituximab with an adjusted hazard ratio of 0.69 (95 per cent confidence interval 0.52 to 0.90, p = 0.0034). The subgroup split is the interesting part: against R-CHOP the hazard ratio was 0.37 (0.22 to 0.62), against bendamustine-rituximab 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.

The practical reading is that the chemotherapy-free option is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab, which is why it is an option rather than a replacement. The median age was 74 and three-quarters of participants were male, which matches the epidemiology of the disease.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-10-01
- Also known as: Ibrutinib and rituximab versus immunochemotherapy in mantle cell lymphoma; ENRICH trial; EudraCT 2015-000832-13
- Tags: lymphoma-evidence
- Phase: 2/3
- Setting: Aged 60 or over with untreated stage II to IV mantle cell lymphoma: ibrutinib with rituximab against rituximab with R-CHOP or bendamustine
- Sponsor: Cancer Research UK and Johnson and Johnson Pharmaceuticals
- Enrolled: 397
- Result: Progression-free survival adjusted hazard ratio 0.69 (p = 0.0034) for ibrutinib with rituximab against immunochemotherapy, driven by the comparison against R-CHOP (0.37) rather than against bendamustine-rituximab (0.91).
- Outcomes: Progression-free survival: Ibrutinib with rituximab vs Rituximab with R-CHOP or bendamustine, HR 0.69; Progression-free survival, R-CHOP stratum: Ibrutinib with rituximab vs R-CHOP, HR 0.37; Progression-free survival, bendamustine-rituximab stratum: Ibrutinib with rituximab vs Bendamustine with rituximab, HR 0.91
- Replication: The first randomised test of this question; SHINE and ECHO tested the opposite strategy of adding the inhibitor to chemotherapy.

## Sources

- Lancet 2025: https://doi.org/10.1016/S0140-6736(25)01432-1
- EU Clinical Trials Register 2015-000832-13: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-000832-13

## Connected records

- cancers: [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CCND1](https://onco.cc/targets/ccnd1/), [CD20](https://onco.cc/targets/cd20/)
- drugs: [Bendamustine](https://onco.cc/drugs/bendamustine/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rituximab](https://onco.cc/drugs/rituximab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- institutions: [Cancer Research UK](https://onco.cc/institutions/cruk/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/)
- terms: [Maintenance therapy](https://onco.cc/terms/maintenance-therapy/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/)
- trials: [A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL](https://onco.cc/trials/nct02972840/), [SHINE](https://onco.cc/trials/shine/), [TRIANGLE](https://onco.cc/trials/triangle/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma](https://onco.cc/key-papers/paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025/), [Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial](https://onco.cc/key-papers/paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025/), [Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma](https://onco.cc/key-papers/paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022/)
- roadmaps: [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](https://onco.cc/roadmaps/lymphoma-roadmap/)
- ideas: [Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas](https://onco.cc/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/)

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