P006 | THE SHORT-TERM DOSE-DENSE CARMEN PROGRAM IS ASSOCIATED WITH BETTER TOLERABILITY AND SIMILAR EFFICACY THAN OTHER INTENSIFIED REGIMENS IN PATIENTS WITH HIGH-GRADE B-CELL LYMPHOMAS

Introduction. High-grade B-cell lymphoma (HGBCL) patients (pts) exhibits poor outcomes after RCHOP and used intensified regimens need long delivery time and show relevant dose-limiting toxicities and treatment-related mortality (TRM). The “CARMEN” program showed encouraging safety and efficacy results in MYC-rearranged lymphomas. Herein, we retrospectively analyzed toxicity and efficacy of RCHOP, CARMEN and other four intensified regimens in HGBCLs treated at the six Italian centers where CARMEN was developed. Methods. Consecutive HGBCL pts (18-75 years) treated between 2010 and 2024 who received at least one dose of chemotherapy were considered. Inclusion criteria were concomitant: diagnosis performed by local expert pathologists according to ICC/WHO5 classifications as well as availability of FISH for MYC, BCL-2, and BCL-6. CARMEN details were previously reported [Ferreri et al. Blood Adv 2022]. Results. 156 pts were analyzed: 57 (37%) pts had DHL-BCL2 lymphoma, 21 (13%) had DHL-BCL6, and 78 (50%) had HGBCL not otherwise specified (HGBCL NOS). 28 (18%) pts had HIV infection. Treatment consisted of RCHOP in 25 pts, R-daEPOCH in 55, CODOXM/IVAC or HyperCVAD in 17, GMALL in 20, and CARMEN in 39. Pts features were balanced among therapeutic subgroups (Table). CARMEN compared well with the other intensified regimens in terms of toxic deaths (10% vs. 12%), dose reductions/interruptions (31% vs. 34%), grade 3-4 non-hematological toxicity (33% vs. 32%), grade 3-4 infections (36% vs. 42%), and grade 3-4 opportunistic infections (8% vs. 7%). CARMEN showed more favorable tolerability profiles in HIV-positive pts, where TRM was 0% vs. 27% (p= 0.03), with dose reductions/interruptions in 14% vs. 55% (p= 0.03). At a median follow-up of 48 months (IQR 26-71), 78 (50%) pts experienced a PFS event and 68 (44%) died, with a 5-year PFS of 48% (95%CI=43-52) and OS of 52% (95%CI= 48-56). OS was similar after RCHOP and intensified regimens (5-year OS: 56%; 95%CI= 49-53 and 51%; 95%CI= 47-55) and after the latter group and CARMEN (5-year: 56%; 95%CI= 52-59 and 48%; 95%CI= 39-57) (figure). In multivariate analysis, age, PS, and transformation from indolent lymphomas, were independent predictors of PFS and OS. Conclusions. Exploiting its limited exposition to cytostatics and short duration, CARMEN regimen shows similar tolerability and efficacy than other intensified regimens. This cost-benefit treatment may be the backbone for future combinations to treat HGBCLS.