Introduction: The growing body of evidence around sexual and gender dimorphism in medicine, particularly in oncology, has highlighted differences in treatment response, outcomes, and side effects between males and females. Differences in drug metabolism, distribution, and elimination, influenced by factors like body composition and enzyme expression, contribute to these variations. Methods: We retrospectively analyzed data of 112 multiple myeloma (MM) patients treated with first-line high-dose chemotherapy (HDCT) with treosulfan and melphalan (TreoMel) followed by autologous stem cell transplantation (ASCT) at a single academic center between January 2020 and August 2022. We assessed response rate, progression-free survival (PFS), overall survival (OS), and toxicities in relation to gender and treosulfan exposure. Results: Our analysis revealed significant gender-specific differences in treosulfan exposure. Females had higher peak levels (343.8 vs. 309.0 mg/L,p= 0.0011) and area under the curve (AUC) (869.9 vs. 830.5 mg*h/L,p= 0.0427) compared to males. Higher treosulfan exposure was associated with increased mortality in females but not in males. Females with treosulfan AUC > 900 mg*h/L had significantly shorter overall survival, while PFS was unaffected by treosulfan exposure. Conclusion: Our study demonstrates that female patients undergoing TreoMel HDCT have higher treosulfan exposure than males and that females with higher levels are at increased risk for toxicity and adverse outcomes. These data suggest that higher treosulfan doses do not confer a benefit in terms of better outcomes for females. Therefore, exploring lower treosulfan doses for female MM patients undergoing TreoMel HDCT may be warranted to mitigate toxicity and improve outcomes.
引言：医学领域，特别是肿瘤学中，关于性与性别二态性的证据日益增多，凸显了男性和女性在治疗反应、预后及副作用方面存在的差异。这些差异受到身体成分和酶表达等因素的影响，体现在药物代谢、分布和清除等方面。方法：我们回顾性分析了2020年1月至2022年8月期间，在单一学术中心接受一线大剂量化疗（HDCT）——曲奥舒凡联合美法仑（TreoMel）序贯自体干细胞移植（ASCT）治疗的112例多发性骨髓瘤（MM）患者数据。我们评估了与性别及曲奥舒凡暴露水平相关的缓解率、无进展生存期（PFS）、总生存期（OS）及毒性反应。结果：我们的分析揭示了曲奥舒凡暴露水平存在显著的性别特异性差异。与男性相比，女性患者的血药峰浓度（343.8 vs. 309.0 mg/L, p=0.0011）和曲线下面积（AUC）（869.9 vs. 830.5 mg*h/L, p=0.0427）均更高。较高的曲奥舒凡暴露水平与女性患者死亡率增加相关，但在男性患者中未观察到这种关联。曲奥舒凡AUC > 900 mg*h/L的女性患者总生存期显著缩短，而无进展生存期则不受曲奥舒凡暴露水平影响。结论：我们的研究表明，接受TreoMel HDCT治疗的女性患者比男性患者具有更高的曲奥舒凡暴露水平，且暴露水平较高的女性患者发生毒性和不良结局的风险增加。这些数据表明，较高的曲奥舒凡剂量并未为女性患者带来更好的预后获益。因此，对于接受TreoMel HDCT治疗的多发性骨髓瘤女性患者，探索降低曲奥舒凡剂量可能有助于减轻毒性并改善预后。
肿瘤(癌症)患者之家