Developing a score system to predict therapeutic outcomes to anti-PD-1 immunotherapy in metastatic melanoma

Alice Indini, Lorenza Di Guardo, Carolina Cimminiello, Michele Prisciandaro, Giovanni Randon, Filippo De Braud, Michele Del Vecchio

Research output: Contribution to journalArticle

Abstract

Background: Prognosis of patients with metastatic melanoma has improved due to the advent of antibodies targeting the programmed cell death protein-1 (PD-1). However, therapeutic outcomes from anti-PD-1 therapy widely differ among patients. Biomarkers for outcome are needed as these may influence patient selection and treatment decision. Methods: Data of patients with metastatic melanoma treated with anti-PD-1 were retrospectively reviewed. Baseline biochemical (serum lactate dehydrogenase [LDH] levels, complete blood count) and clinical characteristics were evaluated to identify predictors of progression-free survival (PFS) and overall survival (OS). PFS and OS were assessed using Kaplan-Meier and Cox models. The comparison of predictive power of independent predictors for response to anti-PD-1 was evaluated by receiver operating characteristic (ROC) curves. Results: Overall, 173 patients were included. Low metastases burden, normal baseline LDH levels, and high relative lymphocyte count (RLC) were associated with favorable outcomes (p < 0.01). According to ROC curves, RLC >17.5% improved survival outcomes. PFS was 3.7 and 15.8 months for patients with RLC <17.5% and >17.5%, respectively (p = 0.004); OS was 5.0 and 33.6 months for patients with RLC <17.5% and >17.5%, respectively (p < 0.001). Stratification of patients according to these variables showed that survival outcomes strongly differ in patients with 3 of 3 compared to those with 2, 1, and none of these 3 factors present (p < 0.001). Conclusions: Metastases burden, LDH levels, and RLC are independent baseline characteristics associated with outcome in patients with melanoma receiving anti-PD-1. Further investigations are needed to clarify if evaluation of these parameters can translate into clinical strategy and apply to patient selection.

Original languageEnglish
JournalTumori
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Immunotherapy
Melanoma
Lymphocyte Count
L-Lactate Dehydrogenase
Survival
Disease-Free Survival
Therapeutics
Patient Selection
Programmed Cell Death 1 Receptor
Neoplasm Metastasis
Blood Cell Count
Proportional Hazards Models
ROC Curve
Biomarkers
Antibodies
Serum

Keywords

  • anti-PD-1
  • immunotherapy
  • LDH
  • leukocytes
  • Melanoma
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Developing a score system to predict therapeutic outcomes to anti-PD-1 immunotherapy in metastatic melanoma. / Indini, Alice; Di Guardo, Lorenza; Cimminiello, Carolina; Prisciandaro, Michele; Randon, Giovanni; De Braud, Filippo; Del Vecchio, Michele.

In: Tumori, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Prognosis of patients with metastatic melanoma has improved due to the advent of antibodies targeting the programmed cell death protein-1 (PD-1). However, therapeutic outcomes from anti-PD-1 therapy widely differ among patients. Biomarkers for outcome are needed as these may influence patient selection and treatment decision. Methods: Data of patients with metastatic melanoma treated with anti-PD-1 were retrospectively reviewed. Baseline biochemical (serum lactate dehydrogenase [LDH] levels, complete blood count) and clinical characteristics were evaluated to identify predictors of progression-free survival (PFS) and overall survival (OS). PFS and OS were assessed using Kaplan-Meier and Cox models. The comparison of predictive power of independent predictors for response to anti-PD-1 was evaluated by receiver operating characteristic (ROC) curves. Results: Overall, 173 patients were included. Low metastases burden, normal baseline LDH levels, and high relative lymphocyte count (RLC) were associated with favorable outcomes (p < 0.01). According to ROC curves, RLC >17.5{\%} improved survival outcomes. PFS was 3.7 and 15.8 months for patients with RLC <17.5{\%} and >17.5{\%}, respectively (p = 0.004); OS was 5.0 and 33.6 months for patients with RLC <17.5{\%} and >17.5{\%}, respectively (p < 0.001). Stratification of patients according to these variables showed that survival outcomes strongly differ in patients with 3 of 3 compared to those with 2, 1, and none of these 3 factors present (p < 0.001). Conclusions: Metastases burden, LDH levels, and RLC are independent baseline characteristics associated with outcome in patients with melanoma receiving anti-PD-1. Further investigations are needed to clarify if evaluation of these parameters can translate into clinical strategy and apply to patient selection.",
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AU - Indini, Alice

AU - Di Guardo, Lorenza

AU - Cimminiello, Carolina

AU - Prisciandaro, Michele

AU - Randon, Giovanni

AU - De Braud, Filippo

AU - Del Vecchio, Michele

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AB - Background: Prognosis of patients with metastatic melanoma has improved due to the advent of antibodies targeting the programmed cell death protein-1 (PD-1). However, therapeutic outcomes from anti-PD-1 therapy widely differ among patients. Biomarkers for outcome are needed as these may influence patient selection and treatment decision. Methods: Data of patients with metastatic melanoma treated with anti-PD-1 were retrospectively reviewed. Baseline biochemical (serum lactate dehydrogenase [LDH] levels, complete blood count) and clinical characteristics were evaluated to identify predictors of progression-free survival (PFS) and overall survival (OS). PFS and OS were assessed using Kaplan-Meier and Cox models. The comparison of predictive power of independent predictors for response to anti-PD-1 was evaluated by receiver operating characteristic (ROC) curves. Results: Overall, 173 patients were included. Low metastases burden, normal baseline LDH levels, and high relative lymphocyte count (RLC) were associated with favorable outcomes (p < 0.01). According to ROC curves, RLC >17.5% improved survival outcomes. PFS was 3.7 and 15.8 months for patients with RLC <17.5% and >17.5%, respectively (p = 0.004); OS was 5.0 and 33.6 months for patients with RLC <17.5% and >17.5%, respectively (p < 0.001). Stratification of patients according to these variables showed that survival outcomes strongly differ in patients with 3 of 3 compared to those with 2, 1, and none of these 3 factors present (p < 0.001). Conclusions: Metastases burden, LDH levels, and RLC are independent baseline characteristics associated with outcome in patients with melanoma receiving anti-PD-1. Further investigations are needed to clarify if evaluation of these parameters can translate into clinical strategy and apply to patient selection.

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