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. 2023 Jul;6(7):e1760.
doi: 10.1002/cnr2.1760. Epub 2022 Dec 9.

Prognostic factors of toxicity of immune checkpoint inhibitors in nonsmall cell lung cancer and small cell lung cancer patients: The ToxImmune study

Francoise Difoum  1 , Antoine Schernberg  1 , Hélène Vanquaethem  2 , Hugo Picchi  3 , Audrey Le Roy  3 , Perrine Vuagnat  1 , Carole Helissey  1   3
Affiliations

Prognostic factors of toxicity of immune checkpoint inhibitors in nonsmall cell lung cancer and small cell lung cancer patients: The ToxImmune study

Francoise Difoum et al. Cancer Rep (Hoboken). 2023 Jul.

Abstract

Background: Immunotherapy alone or in combination has clearly improved the survival of patients with lung cancer. However, it may also be responsible for adverse events impacting these patients' quality of life. The ToxImmune study aims to identify prognostic factors that can help to predict immune-related adverse events.

Methods: We included all patients aged 18 years and older who had received at least one dose of immune checkpoint inhibitors, with or without other therapy, between June 2015 and December 2020 and were diagnosed with nonsmall cell lung cancer or small-cell lung cancer. Patients' baseline demographic characteristics, biological blood markers, and imaging by PET-scanner were collected from electronic medical records. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Events V.5.0).

Results: Sixty-four patients were included, of whom 60 (94%) presented at least one irAE. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and grade 3-4 was 34% and 8% respectively. Female sex, Primitive Tumor Standardized Uptake Value Max (SUVmax) <5, number of metastases ≥3 and immunotherapy received after the first line were found to be significant risk factors for immune-related adverse events. Based on the number of risk factors, the ToxImmune score predicts the risk of having a grade ≥2 adverse event (primitive tumor SUV ≥ 5 = 0 vs. primitive tumor SUV <5 = 1, number of metastases <3 = 0 vs. number of metastases ≥3 = 1 and L1 = 0 vs. L1 ≥ 1). The incidence of grade ≥2 adverse events was 20%, 55% and 90% with ToxImmune scores 0, 1 and = 2 respectively (p = .003). Median progression-free survival (PFS) times were 19.2 months, 6.64 months and 2.63 months for ToxImmune scores 0, 1 and = 2 respectively, p = .13. Median overall survival times were 22.6 months, 16.4 months and 9.8 months for ToxImmune scores 0, 1 and ≥2 respectively, p = .24. The disease control rate (DRR) was 78% in ToxIummune score 0 group, and 50% in ToxImmune score 1 and ≥2 groups (p = .363).

Conclusion: The ToxImmune score, which is grounded on objective clinical parameters, indicates that cases with a high score had an advanced threat of severe adverse events. The ToxImmune score could therefore be used in clinical practice to identify patients treated for lung cancer with immunotherapy and at risk of severe AE.

Keywords: immune-related adverse events; immunotherapy; lung cancer.

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Conflict of interest statement

The authors declare no conflict of interest with this work.

Figures

FIGURE 1
FIGURE 1
Toxicity by ToxImmune score
FIGURE 2
FIGURE 2
Overall response rate by ToxImmune score. PD, progression disease; RC, complete response; RP, partial response; SD, stable disease
FIGURE 3
FIGURE 3
(A) PFS by AE grade. (B) OS by AE grade
FIGURE 4
FIGURE 4
(A) PFS by ToxImmune score. (B) OS by ToxImmune score.
See this image and copyright information in PMC

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