# Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas

Source: https://onco.cc/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/  
OnCo record `lymphoma-ev-fixed-duration-chemotherapy-free-first-line` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Several treatments now work without chemotherapy, but most are given until the disease comes back. Giving them for a fixed time and stopping is the version patients would choose.

## Summary

Two trials now recruiting bear directly on it: the National Cancer Institute comparison of fixed-duration mosunetuzumab against rituximab in low tumour burden follicular lymphoma, and the European trial of mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma. Neither is designed with time off treatment as a primary endpoint, which is the gap. The payer argument is the same as the patient argument here, which is unusual and worth using.

## Fields

- Kind: Idea
- Last checked: 2026-10-01
- Also known as: Chemotherapy-free first line in follicular and mantle cell lymphoma; Time-limited bispecific antibody therapy
- Tags: lymphoma-evidence
- Hypothesis: A fixed-duration, chemotherapy-free first-line regimen in follicular, marginal zone and mantle cell lymphoma achieves progression-free survival comparable to continuous or chemotherapy-containing treatment, with lower cumulative toxicity, lower cost and more time off treatment.
- Rationale: ENRICH showed that ibrutinib with rituximab beats immunochemotherapy in older mantle cell lymphoma, but ibrutinib continues until progression. SHINE and ECHO both gained progression-free survival with indefinite Bruton tyrosine kinase inhibition and neither extended life. Mosunetuzumab is given for a fixed duration and odronextamab until progression, with complete response rates of 73.4 per cent for the latter in relapsed follicular lymphoma. RELEVANCE already showed a chemotherapy-free first line can match immunochemotherapy. The open question is whether stopping is safe.
- Proposed test: Randomise fixed-duration against continuous therapy within the same chemotherapy-free backbone, with retreatment at progression permitted in the fixed-duration arm, and measure time to second progression or next treatment rather than first progression. Co-primary endpoints should include total months on treatment and patient-reported outcomes, because those are the quantities the strategy is meant to change.
- Maturity: being-tested-at-scale
- Actor: research

## 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: [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CD20](https://onco.cc/targets/cd20/), [CD3](https://onco.cc/targets/cd3/)
- drugs: [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Mosunetuzumab](https://onco.cc/drugs/mosunetuzumab/), [Odronextamab](https://onco.cc/drugs/odronextamab/), [Rituximab](https://onco.cc/drugs/rituximab/)
- terms: [Maintenance and consolidation in lymphoma: where it works and where it does not](https://onco.cc/terms/lymphoma-tx-maintenance/), [Watchful waiting, and how it differs from active surveillance](https://onco.cc/terms/watchful-waiting/)
- trials: [ENRICH](https://onco.cc/trials/enrich/), [Mosunetuzumab against rituximab in low tumour burden follicular lymphoma](https://onco.cc/trials/mosun-lbt-fl/), [Mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma](https://onco.cc/trials/mosun-len-mzl/), [RELEVANCE](https://onco.cc/trials/relevance/)
- bottlenecks: [Patients lack understanding, navigation and agency](https://onco.cc/bottlenecks/b-patient-voice/), [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/), [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/), [Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma](https://onco.cc/key-papers/paper-elm-2-odronextamab-follicular-ann-oncol-2024/)

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