# Lymphoma treatments that did not work: the negative trials worth knowing

Source: https://onco.cc/terms/lymphoma-tx-failed-and-negative/  
OnCo record `lymphoma-tx-failed-and-negative` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A list of things that were expected to improve lymphoma treatment and did not. Knowing them is how a patient can tell a reasonable suggestion from an outdated one.

## Summary

More intensive first-line chemotherapy for diffuse large B-cell lymphoma. Alliance/CALGB 50303 randomised 491 patients to DA-EPOCH-R or R-CHOP and found no difference in progression-free survival (hazard ratio 0.93) or overall survival, with more febrile neutropenia (35.0 against 17.7 per cent), mucositis and neuropathy. DA-EPOCH-R therefore has a place in specific diseases, not as a general upgrade.

A better antibody. GOYA randomised 1,418 patients to obinutuzumab-CHOP or R-CHOP in untreated diffuse large B-cell lymphoma: three-year progression-free survival 70 against 67 per cent, hazard ratio 0.92, not significant, with more grade 3 to 5 adverse events. Obinutuzumab does help in follicular lymphoma (GALLIUM) and does not help in diffuse large B-cell lymphoma.

Maintenance after R-CHOP. REMARC improved progression-free survival with lenalidomide but not overall survival, at the cost of neutropenia in 56 per cent.

Second-line CAR-T, once. BELINDA randomised tisagenlecleucel against salvage chemotherapy and transplant in early relapse and was negative (event-free survival hazard ratio 1.07), while ZUMA-7 and TRANSFORM with different products and shorter manufacturing times were strongly positive. Product and pathway, not the idea, explain the difference.

Radiotherapy dose reduction in indolent lymphoma. FoRT found 4 Gy in two fractions clearly inferior to 24 Gy for local control, so the low dose is palliative only.

CNS prophylaxis. Neither intrathecal nor systemic high-dose methotrexate reduced central nervous system relapse below the rate predicted by CNS-IPI in the largest study of patients who received it.

An approval that has not converted. Glofitamab with gemcitabine and oxaliplatin improved overall survival in STARGLO (25.5 against 12.9 months) and NICE TA1113 allows it in England at second line for transplant-ineligible patients, but glofitamab's only United States indication is still the accelerated approval of 15 June 2023 for disease after two or more lines. The same evidence has produced different access in different countries.

## Fields

- Kind: Term
- Last checked: 2026-09-29
- Also known as: Negative lymphoma trials; Failed lymphoma regimens

## Sources

- Alliance/CALGB 50303, Journal of Clinical Oncology 2019: https://doi.org/10.1200/JCO.18.01994
- GOYA: obinutuzumab-CHOP against R-CHOP, Journal of Clinical Oncology 2017: https://doi.org/10.1200/JCO.2017.73.3402
- REMARC, Journal of Clinical Oncology 2017: https://doi.org/10.1200/JCO.2017.72.6984

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/)
- drugs: [Glofitamab](https://onco.cc/drugs/glofitamab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Obinutuzumab](https://onco.cc/drugs/obinutuzumab/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/)
- terms: [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/), [Maintenance and consolidation in lymphoma: where it works and where it does not](https://onco.cc/terms/lymphoma-tx-maintenance/), [Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy](https://onco.cc/terms/lymphoma-tx-radiotherapy/)
- trials: [BELINDA](https://onco.cc/trials/belinda/), [GALLIUM](https://onco.cc/trials/gallium/), [STARGLO](https://onco.cc/trials/starglo/), [TRANSFORM](https://onco.cc/trials/transform/), [ZUMA-7](https://onco.cc/trials/zuma-7/)
- key papers: [FoRT: 4 Gy versus 24 Gy radiotherapy for indolent lymphoma, a randomised phase 3 non-inferiority trial](https://onco.cc/key-papers/paper-fort-4gy-vs-24gy-indolent-lymphoma-hoskin-lancet-oncol-2014/)

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