Table 4_Propensity-matched study of liposomal doxorubicin vs. doxorubicin in first-line DLBCL treatment: efficacy and safety.docx

ObjectiveGiven the increasing use of pegylated liposomal doxorubicin (PLD) in diffuse large B-cell lymphoma (DLBCL) treatment due to its advantages in reducing adverse reactions, and the uncertainty surrounding its effective dose and corresponding efficacy in DLBCL, this study aims to compare it with the standard dose of conventional doxorubicin (DOX) in first-line DLBCL treatment.
MethodsA retrospective propensity score-matched analysis of 512 DLBCL patients (2018–2023) compared PLD {stratified: low-dose [21.5 (5–25.5) mg/m2, n = 71] and high-dose [29.5 (25.5–40) mg/m2, n = 71]} with DOX {low-dose [32.4 (20–40) mg/m2, n = 47]} and standard-dose [49.0 (40–50) mg/m2, n = 323]. Endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.
ResultsOverall PLD and DOX showed comparable 2-year PFS (74.3% vs. 69.6%, P = 0.479, Holm-Bonferroni P = 0.959) and OS (81.4% vs. 83.8%, P = 0.939, Holm-Bonferroni P = 0.959). High-dose PLD demonstrated significantly superior PFS vs. low-dose DOX (79.9% vs. 59.8%, P = 0.0066, Holm-Bonferroni P = 0.0132) and numerically higher PFS vs. overall DOX (81.0% vs. 70.5%, P = 0.354, Holm-Bonferroni P = 0.707), though this did not reach statistical significance. PLD significantly reduced hematologic toxicities (leukopenia: 7.7% vs. 56.7%, P < 0.001) and hepatic dysfunction (alanine aminotransferase elevation: 13.4% vs. 52.8%, P < 0.001), with similar cardiac/pneumonia events. Elderly patients (≥60 years) mirrored overall efficacy/safety trends.
ConclusionHigh-dose PLD [29.5 (25.5–40) mg/m2] offers a safer and potentially more effective alternative to standard DOX, while low-dose PLD maintains equivalent efficacy. These findings support optimized PLD dosing strategies in DLBCL therapy to enhance safety without compromising outcomes.

研究背景与目的：鉴于聚乙二醇脂质体多柔比星（pegylated liposomal doxorubicin，PLD）因在降低不良反应方面的优势，在弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）治疗中的应用日益增多，但其在DLBCL中的有效剂量及对应疗效尚不明确，本研究旨在对比其与标准剂量常规多柔比星（conventional doxorubicin，DOX）一线治疗DLBCL的效果。
研究方法：本研究对2018-2023年的512例DLBCL患者开展回顾性倾向得分匹配分析，将聚乙二醇脂质体多柔比星（PLD）分为低剂量组[21.5（5~25.5）mg/m²，n=71]与高剂量组[29.5（25.5~40）mg/m²，n=71]，同时将常规多柔比星（DOX）分为低剂量组[32.4（20~40）mg/m²，n=47]与标准剂量组[49.0（40~50）mg/m²，n=323]。本研究的终点指标包括无进展生存期（progression-free survival，PFS）、总生存期（overall survival，OS）及毒性反应。
研究结果：整体而言，PLD组与DOX组的2年无进展生存期（74.3% vs. 69.6%，P=0.479，Holm-Bonferroni校正P=0.959）和总生存期（81.4% vs. 83.8%，P=0.939，Holm-Bonferroni校正P=0.959）均无显著统计学差异。高剂量PLD组的无进展生存期显著优于低剂量DOX组（79.9% vs. 59.8%，P=0.0066，Holm-Bonferroni校正P=0.0132）；相较于整体DOX组，高剂量PLD组的无进展生存期数值上更高（81.0% vs. 70.5%，P=0.354，Holm-Bonferroni校正P=0.707），但未达到统计学显著性阈值。与DOX组相比，PLD组的血液学毒性（白细胞减少：7.7% vs. 56.7%，P<0.001）及肝功能异常（丙氨酸氨基转移酶升高：13.4% vs. 52.8%，P<0.001）发生率显著降低，心脏毒性及肺炎事件发生率则无显著差异。老年患者（≥60岁）的疗效及安全性趋势与整体研究人群一致。
研究结论：高剂量PLD[29.5（25.5~40）mg/m²]相较于标准剂量DOX，是一种更安全且潜在疗效更优的治疗选择，而低剂量PLD的疗效与DOX相当。本研究结果支持在DLBCL治疗中优化PLD给药方案，在不降低治疗疗效的前提下提升患者安全性。