# Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma

Source: https://onco.cc/key-papers/paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022/  
OnCo record `paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding a targeted tablet to first-line chemotherapy gave older people with mantle cell lymphoma about two and a half more years before relapse, without helping them live longer.

## Summary

A randomised trial in patients aged 65 or over with untreated mantle-cell lymphoma. 523 patients received ibrutinib 560 mg orally once daily until progression or unacceptable toxicity (261) or placebo (262), plus six cycles of bendamustine 90 mg per square metre and rituximab 375 mg per square metre. Responders received rituximab maintenance every eight weeks for up to twelve additional doses. The primary endpoint was investigator-assessed progression-free survival.

At a median follow-up of 84.7 months, median progression-free survival was 80.6 months with ibrutinib against 52.9 months with placebo (hazard ratio for progression or death 0.75, 95 per cent confidence interval 0.59 to 0.96, p = 0.01). Complete response occurred in 65.5 against 57.6 per cent (p = 0.06). Overall survival was similar in the two groups. Grade 3 or 4 adverse events during treatment occurred in 81.5 against 77.3 per cent.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: SHINE; Wang 2022
- Tags: lymphoma-evidence
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2201817
- Authors: Wang ML, Jurczak W, Jerkeman M, et al.
- Findings: Median progression-free survival was 80.6 months with ibrutinib against 52.9 months with placebo (hazard ratio 0.75, 95 per cent confidence interval 0.59 to 0.96, p = 0.01).; Complete response occurred in 65.5 per cent with ibrutinib against 57.6 per cent with placebo (p = 0.06).; Overall survival was similar in the two groups.; Grade 3 or 4 adverse events during treatment occurred in 81.5 per cent with ibrutinib against 77.3 per cent with placebo.; Median follow-up was 84.7 months.
- What it means: Twenty-eight extra months of progression-free survival, with no survival gain and a high rate of severe adverse events in both arms. It set up the two trials that followed: ECHO, which substituted a more selective inhibitor, and ENRICH, which removed the chemotherapy.
- Caveats: Progression-free survival without an overall survival benefit, in a population whose median age is over 70 and who have competing causes of death.; Continuous ibrutinib until progression means indefinite treatment, with the cardiac and bleeding risks that carries in this age group.; Investigator-assessed primary endpoint in a placebo-controlled trial, which is standard but less robust than central review.

## Sources

- New England Journal of Medicine 2022: https://doi.org/10.1056/NEJMoa2201817
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35657079/
- Europe PMC: https://europepmc.org/article/MED/35657079

## Connected records

- 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/)
- 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/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Rituximab](https://onco.cc/drugs/rituximab/)
- companies: [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/)
- terms: [Maintenance therapy](https://onco.cc/terms/maintenance-therapy/)
- trials: [A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL](https://onco.cc/trials/nct02972840/), [ENRICH](https://onco.cc/trials/enrich/), [SHINE](https://onco.cc/trials/shine/)
- people: [Martin Dreyling](https://onco.cc/people/martin-dreyling/), [Michael L. Wang](https://onco.cc/people/michael-wang/)
- 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/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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