Body mass index and the risk of hematologic adverse events in HR+/HER2- breast cancer patients treated with CDK4/6 inhibitors.

e24150 Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors has been established as the recommended therapy for hormone receptor-positive and human epidermal growth factor 2-negative (HR+/HER2-) breast cancer (BC). However, the evidence on the relation between BMI and CDK4/6 inhibitor-related hematologic adverse advents (AEs) remain limited. Therefore, this study aimed to investigate the association between BMI and the risk of CDK4/6 inhibitor-related AEs in patients with HR+/HER2- BC. Methods: This single-center, retrospective cohort study at Sun Yat-Sen Memorial Hospital between January 8, 2019 and April 1, 2025 included patients with HR+/HER2- BC receiving CDK4/6 inhibitor and had a baseline BMI. Those who were treated with CDK4/6 inhibitors in the neoadjuvant setting or had incomplete clinical data were excluded. BMI was dichotomized based on the Working Group on Obesity in China (WGOC) criteria: <24 kg/m 2 vs. ≥24 kg/m 2 . The primary endpoint was incidence of grade≥3 neutropenia. The secondary endpoints were grade≥3 of overall and other hematological AEs separately, including leukopenia, anemia, thrombocytopenia, and lymphopenia, as defined in version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE). Group differences were assessed using Chi-square or Fisher’s exact tests. The Wald method was used to calculate the rate difference (RD) and 95% confidence interval (CI). Results: Among 740 included HR+/HER2- BC patients, 424 (57.3%) were BMI <24 kg/m 2 and 316 (42.7%) were BMI ≥24 kg/m 2 . Patients with BMI ≥24 kg/m 2 tended to be older and with higher Eastern Cooperative Oncology Group (ECOG) score. There were no significantly statistical differences in the type of CDK4/6 inhibitors used, with more than half of patients using abemaciclib in both groups. Patients with BMI ≥24 kg/m 2 had a significantly lower incidence of grade ≥3 neutropenia (RD = -10.5%, 95% CI = -17.0% to -4.1%, P = .002), along with lower rates of leukopenia (RD = -8.9 %, 95% CI = -14.6% to -3.1%, P = .004). Conclusions: Higher BMI is associated with less severity of CDK4/6 inhibitor-induced hematologic AEs, notably neutropenia and leukopenia. Further studies are needed to elucidate the mechanisms and optimize treatment to minimize these AEs. Association between BMI and grade≥3 hematologic AEs on CDK4/6 inhibitors. Adverse Event BMI<24 kg/m², No. (%) BMI≥24 kg/m², No. (%) Rate Difference, 95% CI (%) P Neutropenia 144 (34.0) 74 (23.4) -10.5 (-17.0 to -4.1) .002 Leukopenia 106 (25.0) 51 (16.1) -8.9 (-14.6 to -3.1) .004 Anemia 21 (5.0) 11 (3.5) -1.5 (-4.4 to 1.4) .33 Thrombocytopenia 15 (3.5) 6 (1.9) -1.6 (-4.0 to 0.7) .18 Lymphopenia 100 (23.6) 70 (22.2) -1.4 (-7.5 to 4.7) .65 Any adverse event 218 (51.4) 140 (44.3) -7.1 (-14.4 to 0.1) .06 BMI=body mass index, AEs=adverse events, CDK=cyclin-dependent kinase.