Marco Donia, Professor at University of Copenhagen, shared a post on LinkedIn:
“Neoadjuvant immunotherapy in melanoma: moving into personalization
Key question: which regimen for which patient?
- Nature Reviews Immunology, Francesca Fallarino and Prof Dr Christian Blank, September 22, 2025
- Immunity, Minke Lucas et al., January 13, 2026
- Nature Medicine, Lotte Hoeijmakers et al., January 28, 2026
Key Points
1. Neoadjuvant immunotherapy is now established
- Beyond proof-of-concept and into routine clinical application in many regions
2. Long-term outcomes support durable benefit
- In PRADO, 5-year EFS was 71% and 5-year OS 86%
- Patients achieving major pathologic response (MPR, <10% live tumor) had particularly favorable outcomes, with 5-year RFS 86% and DMFS 91%
3. Biomarkers may help guide de-escalation and escalation
- Lucas et al. suggest that baseline IFNγ signatures may help uncouple efficacy from toxicity
- In IFNγ-high tumors, MPR was high across regimens (71% with anti-PD-1, 73% with ipi1+nivo3, 78% with ipi3+nivo1), while grade ≥3 irAEs increased (0%, 19%, 44%)
- In IFNγ-low tumors, MPR increased with escalation (29%, 39%, 64%), while grade ≥3 irAEs remained relatively low (14%, 21%, 18%)
4. PRADO provides a practical biomarker example
- Baseline IFNγ and PD-L1 further separated outcomes
- Low IFNγ / low PD-L1: MPR 27%, 5-year EFS 48%
- High IFNγ / high PD-L1: MPR 86%, 5-year EFS 91%
This supports biomarker-guided de-escalation for favorable biology, and escalation or novel combinations for less favorable disease
Take-Home
- Neoadjuvant immunotherapy is now a standard strategy in resectable macroscopic, stage III hashtag#melanoma
- Long-term data support durable benefit, especially in patients achieving MPR
- The field is moving toward biomarker-driven treatment selection
Clinical Implications
- A one-size-fits-all neoadjuvant immunotherapy approach is unlikely to be optimal
Next frontier: validation (who can be safely de-escalated and who needs escalation?) - Next frontier: PRADO also suggests that patients achieving MPR in the ILN may be candidates for surgical de-escalation, a strategy now being prospectively tested in the OMIT and MSLT-3 trials
Many congratulations to all investigators whose extraordinary efforts, especially with investigator-initiated neoadjuvant melanoma trials, are shaping the field, such as Alexander van Akkooi, Georgina Long, Prof Dr Christian Blank and many other esteemed colleagues!”
Other articles featuring Marco Donia on OncoDaily.