# Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma

Source: https://onco.cc/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/  
OnCo record `paper-hodi-ipilimumab-melanoma-nejm-2010` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Blocking the immune brake CTLA-4 was the first treatment ever to prolong life in metastatic melanoma, with about one in five patients alive at two years and a new class of autoimmune side effects.

## Summary

This phase 3 trial randomised 676 patients with previously treated, HLA-A*0201-positive metastatic melanoma in a 3:1:1 ratio to ipilimumab plus a gp100 peptide vaccine, ipilimumab alone, or gp100 alone. The primary endpoint was overall survival. Median OS was 10.0 months with ipilimumab plus gp100 and 10.1 months with ipilimumab alone versus 6.4 months with gp100 (hazard ratios 0.68 and 0.66), with survival curves showing a durable tail. Grade 3-4 immune-related adverse events occurred in 10-15% of ipilimumab-treated patients, and 14 deaths were related to study drugs, 7 from immune-related events. It led to FDA approval in March 2011 and validated James Allison's checkpoint-blockade hypothesis in humans.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2010
- DOI: 10.1056/NEJMoa1003466
- Authors: Hodi FS, O'Day SJ, McDermott DF, et al.
- Findings: 676 previously treated metastatic melanoma patients; ipilimumab + gp100, ipilimumab alone, or gp100 alone (3:1:1).; Median OS 10.0 and 10.1 months with ipilimumab arms vs 6.4 months with gp100; hazard ratios 0.68 and 0.66.; Response rates were low (about 11% for ipilimumab alone) yet survival improved, showing a disconnect between shrinkage and benefit.; Grade 3-4 immune-related adverse events 10-15% with ipilimumab; 7 deaths from immune-related events.; A plateau in the survival curve suggested long-term survivors, later confirmed at about 20% alive at 3 years in pooled analyses.
- What it means: This paper launched the immunotherapy era. It was the first randomised evidence that taking a brake off the immune system could extend life in a solid cancer, and it introduced clinicians to immune-related adverse events and to responses that arrive late or after apparent progression. Ipilimumab alone has since been superseded by PD-1 antibodies and combinations, but every checkpoint programme traces back to this result.
- Caveats: Comparator was a peptide vaccine, not an active therapy, and was itself of uncertain effect.; Restricted to HLA-A*0201-positive patients because of the vaccine.; Response rate was low; benefit concentrated in a minority with durable responses.; Toxicity was substantial and management was still being learned.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1003466
- ClinicalTrials.gov NCT00094653: https://clinicaltrials.gov/study/NCT00094653

## Connected records

- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/), [CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma](https://onco.cc/key-papers/paper-checkmate-067-10-year-nejm-2025/), [KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma](https://onco.cc/key-papers/paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015/), [Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy](https://onco.cc/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/), [Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer](https://onco.cc/key-papers/paper-topalian-anti-pd1-nejm-2012/)
- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [CTLA-4](https://onco.cc/targets/ctla4/)
- drugs: [Ipilimumab](https://onco.cc/drugs/ipilimumab/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- institutions: [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Overall survival (OS)](https://onco.cc/terms/os/)
- people: [F. Stephen Hodi](https://onco.cc/people/f-stephen-hodi/), [James P. Allison](https://onco.cc/people/james-allison/), [Jedd D. Wolchok](https://onco.cc/people/jedd-wolchok/), [Padmanee Sharma](https://onco.cc/people/padmanee-sharma/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [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/)
- ideas: [Treat the draining lymph node before removing it](https://onco.cc/ideas/idea-bio2-lymph-node-immune-priming/)

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