New research presented at the AACR Immuno-Oncology Conference reveals that sustained lymphopenia during neoadjuvant chemo-immunotherapy significantly impacts clinical outcomes in patients with early-stage triple-negative breast cancer (TNBC). The study suggests that monitoring absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) during treatment may help identify patients at risk for inferior response to therapy.

Clinical Takeaway

Patients with early-stage TNBC who develop or maintain lymphopenia during neoadjuvant pembrolizumab plus chemotherapy have significantly lower rates of pathologic complete response (pCR). This finding suggests that lymphocyte monitoring during treatment could serve as a biomarker for therapeutic response and guide clinical decision-making.

Study Design

This retrospective cohort study analyzed 372 patients with stage I-III TNBC diagnosed between 2019-2023 at two comprehensive cancer centers. All patients received at least one cycle of neoadjuvant pembrolizumab plus chemotherapy.

  • Primary endpoint: Association between lymphopenia and pCR
  • NLR cut-off: ≥5 based on previous studies
  • Assessment timepoints: Pre-treatment, cycle 4 day 1 (C4D1), and pre-surgical

Key Findings

Lymphopenia progression during treatment:

  • Baseline: 9.9% had lymphopenia, 9.4% had NLR ≥5
  • C4D1: 15% had lymphopenia, 18.8% had NLR ≥5
  • Pre-surgery: 38.7% had lymphopenia, 21.6% had NLR ≥5

Impact on pathologic complete response:

  • C4D1 lymphopenia: 50% pCR vs 64.3% without lymphopenia (p=0.042)
  • Sustained lymphopenia (baseline and pre-surgery): 37.5% pCR vs 61.5% without sustained lymphopenia (p=0.02)
  • Greater NLR decline from baseline to C4D1 associated with higher pCR rates (p=0.017)
  • Lower median C4D1 NLR values correlated with improved pCR (p=0.0015)

Clinical Implications

✔ Monitor ALC and NLR during neoadjuvant chemo-immunotherapy as potential predictive biomarkers

✔ Sustained lymphopenia may reflect impaired anti-tumor immune responses in early-stage TNBC

✔ Patients with persistent lymphopenia may benefit from alternative therapeutic interventions

✔ Early identification of lymphopenia (by C4D1) could guide treatment modifications

Bottom Line

This study provides compelling evidence that sustained lymphopenia during neoadjuvant chemo-immunotherapy serves as a negative prognostic marker for pCR in early-stage TNBC. The findings suggest that routine monitoring of ALC and NLR could help identify patients who may require intensified or alternative therapeutic strategies. The progressive increase in lymphopenia rates from baseline to pre-surgery highlights the need for interventions to preserve immune function during treatment.

Sources:

  • LeVee A, Yang E, Tsai K, Baclig N, Soliman A, Zhang S, et al. Sustained lymphopenia during neoadjuvant chemo-immunotherapy is associated with worse outcomes in early triple-negative breast cancer. Cancer Immunol Res. 2026;14(2 Suppl):C040. Abstract C040.