# Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy

Source: https://onco.cc/key-papers/paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017/  
OnCo record `paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first randomised trial of first-line drug treatment for MALT lymphoma: the combination of an old tablet and an antibody beat either alone on relapse, and nobody lived longer.

## Summary

A phase 3 trial in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Patients were initially randomised 1 to 1 between chlorambucil 6 mg per square metre daily on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18 and 21 to 22, and the same chlorambucil with rituximab 375 mg per square metre on day 1 of weeks 1, 2, 3, 4, 9, 13, 17 and 21. After the planned enrolment of 252 patients the protocol was amended to a three-arm design in a 1 to 1 to 6 ratio, adding a rituximab monotherapy arm, for a final sample of 454.

At a median follow-up of 7.4 years, five-year event-free survival was 51 per cent (95 per cent confidence interval 42 to 60) with chlorambucil alone, 50 per cent (42 to 59) with rituximab alone and 68 per cent (60 to 76) with the combination (p = 0.0009); the hazard ratio for the combination against chlorambucil was 0.54 (0.38 to 0.77). Progression-free survival was also significantly better with the combination (p = 0.0119). Five-year overall survival was approximately 90 per cent in each arm. No unexpected toxicities were recorded.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: IELSG-19; Zucca 2017
- Tags: lymphoma-evidence
- Journal: Journal of Clinical Oncology
- Year: 2017
- DOI: 10.1200/JCO.2016.70.6994
- Authors: Zucca E, Conconi A, Martinelli G, et al.
- Findings: Five-year event-free survival was 68 per cent (95 per cent confidence interval 60 to 76) with chlorambucil and rituximab, against 51 per cent (42 to 60) with chlorambucil alone and 50 per cent (42 to 59) with rituximab alone (p = 0.0009).; The hazard ratio for event-free survival with the combination against chlorambucil alone was 0.54 (0.38 to 0.77).; Progression-free survival was also significantly better with the combination (p = 0.0119).; Five-year overall survival was approximately 90 per cent in each of the three arms.
- What it means: The only randomised evidence for first-line systemic treatment of MALT lymphoma. It supports the combination when systemic treatment is needed, and the identical survival across arms supports taking time over that decision.
- Caveats: The protocol was amended mid-trial to add a third arm, and the two-arm comparison was analysed and reported before the third arm was unblinded.; Chlorambucil is not the alkylating agent most used today; bendamustine with rituximab has largely replaced it without a randomised comparison in this disease.; Patients whose gastric MALT lymphoma responds to Helicobacter pylori eradication never reach this question.

## Sources

- Journal of Clinical Oncology 2017: https://doi.org/10.1200/JCO.2016.70.6994
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28355112/
- Europe PMC: https://europepmc.org/article/MED/28355112

## Connected records

- key papers: [Regression of primary low-grade gastric MALT lymphoma after eradication of Helicobacter pylori](https://onco.cc/key-papers/paper-wotherspoon-h-pylori-malt-lancet-1993/)
- 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: [Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)](https://onco.cc/cancers/malt-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- targets: [CD20](https://onco.cc/targets/cd20/)
- drugs: [Chlorambucil](https://onco.cc/drugs/chlorambucil/), [Rituximab](https://onco.cc/drugs/rituximab/)
- companies: [International Extranodal Lymphoma Study Group](https://onco.cc/companies/ielsg/)
- trials: [IELSG-19](https://onco.cc/trials/ielsg-19/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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