Early versus late response to PD-1-based immunotherapy in metastatic melanoma

Eur J Cancer. 2024 Oct:210:114295. doi: 10.1016/j.ejca.2024.114295. Epub 2024 Aug 23.

Abstract

Background: Immune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort.

Methods: Patients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR).

Results: Of 522 patients, 8.2 % were EarlyR (n = 43), 19.0 % were LateR (n = 99), 37.0 % had a SD (n = 193) and 35.8 % were NonR (n = 187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95 %-CI=1.14-3.46, p = 0.015), and normal serum CRP (RR=1.59, 95 %-CI=0.93-2.70, p = 0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95 % CI 19.1; NR) and 47.8 months (95 %-CI 36.9; NR) for EarlyR, NR (95 %-CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95 %-CI 1.9; 2.1) and 6.1 months (95 %-CI 4.6; 8.8) for NonR patients.

Conclusion: Less than 10 % of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.

Keywords: Best overall response; CTLA-4; Immune checkpoint inhibition; Immunotherapy; Melanoma; PD-1; PD-L1; Survival; Therapy outcome.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / methods
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / immunology
  • Melanoma* / mortality
  • Melanoma* / pathology
  • Melanoma* / secondary
  • Melanoma* / therapy
  • Middle Aged
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Prospective Studies
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / immunology
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Time Factors

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human