Treatment-related lymphopenia impairs the treatment response of anti-PD-1 therapy in esophageal squamous cell carcinoma

Int Immunopharmacol. 2022 May:106:108623. doi: 10.1016/j.intimp.2022.108623. Epub 2022 Feb 21.

Abstract

Purpose: Great interest has been focused on radiotherapy (RT) with immunotherapy. We sought to investigate the significance of treatment-related lymphopenia (TRL) in esophageal squamous cell carcinoma (ESCC) patients receiving anti-PD-1 therapy and the factors associated with TRL, especially RT.

Methods: 167 patients with ESCC that received anti-PD-1 therapy wereidentified, 72 of them received RT. TRL was defined as absolute lymphocyte count (ALC) < 0.50 × 109 cells/L at the start of immunotherapy and/or during immunotherapy. Depending on the presence of TRL, patients were divided into two groups.

Results: At median follow-up of 6.5 months, the ORR of patients without TRL (n = 65; 38.9%) reached 29.4% while patients (n = 102; 61.1%) with TRL was 23.1%, DCR was 81.4% and 75.4% respectively. Patients with TRL showed shorter progression-free survival (PFS) compared with patients without TRL (median PFS: 4.8 vs. 7.0 months, P = 0.009). Multivariate analyses confirmed TRL is an independent prognostic factor for poorer PFS (HR, 1.855; P = 0.008). RT significantly increased the occurrence of TRL (OR = 0.502, P = 0.035). Patients receiving ICIs < 33.5 days after RT showed a poorer PFS compared to that ≥ 33.5 days (median PFS: 4.1 vs 7.3 months, P = 0.008). The explanation is that patients with shorter time interval had a higher incidence of TRL (P = 0.028).

Conclusion: TRL was an independent predictor of poor outcomes in ESCC patients receiving anti-PD-1 therapy. RT was a key factor affecting TRL. A shorter time interval of < 33.5 days between RT and anti-PD-1 therapy can lead to a poor prognosis by increasing the occurrence of TRL.

Keywords: Circulating lymphocyte; Esophageal squamous cell carcinoma; Immunotherapy; Lymphopenia; Radiotherapy; Treatment-related lymphopenia.

MeSH terms

  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Humans
  • Immunotherapy / adverse effects
  • Lymphocyte Count
  • Lymphopenia* / chemically induced
  • Prognosis
  • Retrospective Studies