# Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma

Source: https://onco.cc/key-papers/paper-rohaas-til-vs-ipilimumab-nejm-2022/  
OnCo record `paper-rohaas-til-vs-ipilimumab-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In a head-to-head trial, tumour-infiltrating lymphocyte therapy halved the risk of progression compared with ipilimumab in melanoma that had mostly already failed PD-1 blockade.

## Summary

This academic phase 3 trial from the Netherlands Cancer Institute and Copenhagen randomised 168 patients with unresectable stage IIIC-IV melanoma, 86% of whom had progressed on anti-PD-1 therapy, to TIL therapy (tumour resection, ex vivo expansion, cyclophosphamide-fludarabine lymphodepletion, infusion and high-dose interleukin-2) or ipilimumab 3 mg/kg. The primary endpoint was progression-free survival. Median PFS was 7.2 versus 3.1 months (hazard ratio 0.50); objective response was 49% versus 21% and complete response 20% versus 7%. Grade 3 or higher adverse events occurred in all TIL patients, driven by chemotherapy and IL-2, and were transient. Median overall survival was 25.8 versus 18.9 months, not statistically significant. It is the first randomised evidence that a cell therapy improves outcomes in a solid tumour.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2210233
- Authors: Rohaas MW, Borch TH, van den Berg JH, et al.
- Findings: 168 patients with advanced melanoma (86% anti-PD-1 refractory); TIL therapy vs ipilimumab.; Median PFS 7.2 vs 3.1 months; hazard ratio 0.50.; Objective response 49% vs 21%; complete response 20% vs 7%.; Median OS 25.8 vs 18.9 months (hazard ratio 0.83, not significant).; Grade 3 or higher adverse events 100% vs 57%, mostly lymphodepletion- and IL-2-related and resolving before discharge.
- What it means: This trial supplied the randomised proof that was missing for TIL therapy and showed academic centres can run cell-therapy phase 3 trials without industry. It supports TIL as a standard option after checkpoint inhibitor failure in melanoma and underpinned reimbursement in the Netherlands. The comparator, ipilimumab, is itself only modestly effective in this setting, and overall survival did not differ significantly.
- Caveats: Ipilimumab monotherapy is a weak comparator in PD-1-refractory melanoma.; Overall survival benefit was not statistically significant; crossover was allowed.; Severe but transient toxicity requiring inpatient care.; Academic manufacturing at two centres; scalability and reproducibility outside them are unproven.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2210233
- ClinicalTrials.gov NCT02278887: https://clinicaltrials.gov/study/NCT02278887

## Connected records

- key papers: [C-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed](https://onco.cc/key-papers/paper-c-144-01-lifileucel-melanoma-jco-2021/)
- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [TIL therapy](https://onco.cc/technologies/til-therapy/)
- targets: [CTLA-4](https://onco.cc/targets/ctla4/)
- drugs: [Aldesleukin (high-dose IL-2)](https://onco.cc/drugs/aldesleukin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Lifileucel](https://onco.cc/drugs/lifileucel/), [Tacquell (autologous melanoma-derived tumour-infiltrating lymphocytes)](https://onco.cc/drugs/tacquell/)
- institutions: [Netherlands Cancer Institute (NKI-AvL)](https://onco.cc/institutions/nki/)
- terms: [Progression-free survival (PFS)](https://onco.cc/terms/pfs/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- people: [Inge Marie Svane](https://onco.cc/people/inge-marie-svane/), [John Haanen](https://onco.cc/people/john-haanen/), [Ton Schumacher](https://onco.cc/people/ton-schumacher/)
- bottlenecks: [Funding follows fashion, not burden](https://onco.cc/bottlenecks/b-funding-allocation/), [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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