Comparative Effectiveness of R‐miniCOMP Versus R‐miniCHOP in Older Non‐Fit Patients With Diffuse Large B‐Cell Lymphoma: Insights From a “Fondazione Italiana Linfomi” Cohort Study

ABSTRACT The R‐miniCHOP regimen is the standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL) in older unfit or frail patients. Recent research suggests that replacing doxorubicin with non‐PEGylated liposomal doxorubicin (NPLD) is safe and effective for DLBCL. However, the outcomes of DLBCL patients receiving NPLD as part of a reduced‐intensity regimen approach have yet to be investigated. This study aimed to assess non‐fit DLBCL patients enrolled in the Elderly Project (EP) conducted by the Fondazione Italiana Linfomi (FIL) who were treated with R‐miniCHOP or R‐miniCOMP. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS), respectively. Of the 1163 cases within the EP cohort, we identified 176 patients (18%) who resulted unfit or frail at simplified geriatric assessment (sGA) and received either R‐miniCHOP (89 cases; 51%) or R‐miniCOMP (87 cases; 49%). Both cohorts exhibited similar clinical characteristics, a similar distribution of unfit and frail cases using the sGA and similar Elderly Prognostic Index (EPI) scores. After a median follow‐up of 28 months, the 3‐year OS and PFS rates were 61% and 54% respectively, with no significant difference between R‐miniCHOP and R‐miniCOMP. Notably, the therapeutic regimen had no significant impact on OS (HR 1.07, 95% CI: 0.63–1.82, p  = 0.798) or PFS (HR 1.00, 95% CI: 0.62–1.6, p  = 0.999) even after adjusting for propensity score (PS) and inverse probability weighting (IPW). A comprehensive survival analysis within vulnerable geriatric categories (unfit and frail patients) confirmed non‐significant variations in predictive efficacy between R‐miniCHOP and R‐miniCOMP. Of note the independent prognostic role of EPI is confirmed for both OS and PFS. This study suggests that R‐miniCHOP is still the preferred treatment for unfit and frail older DLBCL. The role of R‐miniCOMP for specific subgroups of older DLBCLs warrants confirmation in larger studies.