Propensity-matched study of liposomal doxorubicin vs. doxorubicin in first-line DLBCL treatment: efficacy and safety

Objective Given 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. Methods A retrospective propensity score-matched analysis of 512 DLBCL patients (2018–2023) compared PLD {stratified: low-dose [21.5 (5–25.5) mg/m 2 , n = 71] and high-dose [29.5 (25.5–40) mg/m 2 , n = 71]} with DOX {low-dose [32.4 (20–40) mg/m 2 , n = 47]} and standard-dose [49.0 (40–50) mg/m 2 , n = 323]. Endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results Overall 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. Conclusion High-dose PLD [29.5 (25.5–40) mg/m 2 ] 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.