Heini Alexander D, Kammermann Karin, Bacher Ulrike, Jeker Barbara, Hayoz Michael, Aebi Yolanda, Largiadèr Carlo R, Nilius Henning, Pabst Thomas
Department of Medical Oncology, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland.
Department of Hematology and Central Hematology Laboratory, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland.
Cancers (Basel). 2024 Oct 1;16(19):3364. doi: 10.3390/cancers16193364.
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.
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.
Our analysis revealed significant gender-specific differences in treosulfan exposure. Females had higher peak levels (343.8 vs. 309.0 mg/L, = 0.0011) and area under the curve (AUC) (869.9 vs. 830.5 mgh/L, = 0.0427) compared to males. Higher treosulfan exposure was associated with increased mortality in females but not in males. Females with treosulfan AUC > 900 mgh/L had significantly shorter overall survival, while PFS was unaffected by treosulfan exposure.
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.
医学领域，尤其是肿瘤学领域，关于性与性别二态性的证据越来越多，这凸显了男性和女性在治疗反应、结果及副作用方面的差异。受身体组成和酶表达等因素影响，药物代谢、分布和消除的差异导致了这些变化。
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）联合苏消安和美法仑（TreoMel）随后进行自体干细胞移植（ASCT）的112例多发性骨髓瘤（MM）患者的数据。我们评估了与性别和苏消安暴露相关的缓解率、无进展生存期（PFS）、总生存期（OS）及毒性。
我们的分析显示，在苏消安暴露方面存在显著的性别特异性差异。与男性相比，女性的峰值水平更高（343.8对309.0 mg/L，P = 0.0011），曲线下面积（AUC）也更大（869.9对830.5 mgh/L，P = 0.0427）。较高的苏消安暴露与女性死亡率增加相关，但与男性无关。苏消安AUC > 900 mgh/L的女性总生存期显著缩短，而PFS不受苏消安暴露影响。
我们的研究表明，接受TreoMel HDCT的女性患者苏消安暴露高于男性，且水平较高的女性毒性和不良结局风险增加。这些数据表明，较高的苏消安剂量对女性而言并不能带来更好的结局。因此，对于接受TreoMel HDCT的女性MM患者，探索更低的苏消安剂量以减轻毒性并改善结局可能是有必要的。
