High-dose pegylated liposomal doxorubicin shows comparable survival to conventional doxorubicin in DLBCL with reduced toxicity

This retrospective cohort study analyzed 512 patients with diffuse large B-cell lymphoma (DLBCL) treated between 2018 and 2023. Patients received either pegylated liposomal doxorubicin (PLD), stratified into low-dose (median 21.5 mg/m², n=71) and high-dose (median 29.5 mg/m², n=71) groups, or conventional doxorubicin (DOX), stratified into low-dose (median 32.4 mg/m², n=47) and standard-dose (median 49.0 mg/m², n=323) groups. The primary outcome was not reported; secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity.

For the overall comparison, 2-year PFS was 74.3% for PLD versus 69.6% for DOX (P=0.479), and 2-year OS was 81.4% versus 83.8% (P=0.939), showing no statistically significant differences. In a specific subgroup analysis, high-dose PLD showed superior 2-year PFS compared to low-dose DOX (79.9% vs. 59.8%, P=0.0066). High-dose PLD also showed a numerically higher 2-year PFS compared to overall DOX (81.0% vs. 70.5%), but this was not statistically significant (P=0.354).

PLD was associated with significantly reduced hematologic and hepatic toxicities. Leukopenia occurred in 7.7% of PLD patients versus 56.7% of DOX patients (P<0.001), and alanine aminotransferase elevation occurred in 13.4% versus 52.8% (P<0.001). Cardiac and pneumonia events were similar between groups. Key limitations include the retrospective design, which introduces potential for selection bias and confounding. Follow-up duration, funding sources, and conflicts of interest were not reported.

For practice, these observational data suggest high-dose PLD may offer a safety advantage over conventional DOX in DLBCL therapy, with comparable survival outcomes in the overall cohort. The finding that high-dose PLD was superior to low-dose DOX in a subgroup analysis is hypothesis-generating but requires confirmation. Clinicians should interpret these results cautiously, as they do not establish causality and need validation in prospective, randomized trials.