Abstract C040: Sustained lymphopenia during neoadjuvant chemo-immunotherapy is associated with worse outcomes in early triple-negative breast cancer

Abstract Background: Baseline and relative lymphopenia (as defined by a high neutrophil-to-lymphocyte [NLR] ratio) is associated with poor prognosis in metastatic breast cancer. The clinical impact of changes in lymphopenia during neoadjuvant chemo-immunotherapy in patients with early-stage triple-negative breast cancer (TNBC) is not known. Methods: In this retrospective cohort study, patients with stage I-III TNBC diagnosed between 2019 to 2023 were included who were treated with at least one cycle of neoadjuvant pembrolizumab and chemotherapy at two comprehensive cancer centers. Pre-treatment, cycle 4 day 1 (C4D1), and pre-surgical laboratory values were collected. Lymphopenia was defined as an absolute lymphocyte count (ALC) < 1000/mcL. An NLR cut-off value of 5 was used based on previous studies. On-treatment values of NLR and ALC were analyzed according to pathologic complete response (pCR), a robust surrogate marker for survival. Results: Of the 372 patients with early-stage TNBC included, 9.9% had lymphopenia and 9.4% had NLR >=5 at baseline. At C4D1, 15% had lymphopenia and 18.8% had NLR >=5. Prior to surgery, 38.7% had lymphopenia and 21.6% had NLR >=5. C4D1 lymphopenia was associated with inferior pCR rates compared to those without C4D1 lymphopenia (50% vs. 64.3%; p=0.042). A greater decline in NLR values from baseline to C4D1 (p=0.017) and lower median C4D1 NLR values (p=0.0015) were also associated with higher pCR rates. There was a trend towards lower pCR rates for C4D1 NLR >=5 compared to NLR <5 (52.2% vs. 64.4%; p=0.065). While median pre-surgical ALC and NLR values were not predictive of pCR, patients with lymphopenia at both baseline and pre-surgery were less likely to achieve pCR compared to those without (37.5% vs. 61.5%; p=0.02), highlighting the deleterious impact of sustained lymphopenia on clinical outcomes. Conclusions: Sustained lymphopenia throughout neoadjuvant chemo-immunotherapy is associated with inferior pCR in patients with early-stage TNBC. Favorable changes in NLR from baseline to C4D1 is also associated with improved pCR. This study demonstrates that sustained lymphopenia and the development of relative lymphopenia during neoadjuvant chemo-immunotherapy may reflect impaired anti-tumor immune responses in patients with early-stage TNBC, highlighting the need for therapeutic interventions in this setting. Citation Format: Alexis LeVee, Eric Yang, Karen Tsai, Nikita Baclig, Andrew Soliman, Shiliang Zhang, Austin Kordic, Joanne Mortimer, Hope S. Rugo, Melissa Lechner, Samer Alkassis, Nicholas McAndrew, Marla Lipsyc-Sharf, Mina Sedrak, Rena Callahan, Aashini Master, Diane Prager, Kelly McCann, Aditya Bardia. Sustained lymphopenia during neoadjuvant chemo-immunotherapy is associated with worse outcomes in early triple-negative breast cancer [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C040.