The impact of high-grade B-cell lymphoma morphology compared with diffuse large B-cell lymphoma in a cohort from bra-DLBCL, a multicenter, real-world study from Brazil

Abstract AbstractIntroduction High-grade B-cell lymphoma (HGBL), not otherwise specified (NOS), is an aggressive B-cell lymphoma, recently introduced as a separate entity in the 5th World Health Organization Classification for Haematolymphoid Tumors. Although this new category does not have specific genetics, it includes lymphomas with Burkitt-like or blastoid morphology that cannot be classified as other well-defined lymphoma subtypes. To our knowledge, there is no data on HGBL in low and middle-income countries. This study aimed to describe clinical characteristics and outcomes of patients with HGBL morphology in Brazil and compare it with diffuse large B-cell lymphoma (DLBCL).Methods BRA-DLBCL is a Brazilian multicenter retrospective observational study aimed at generating real-world data (RWD) in patients with newly diagnosed DLBCL and HGBL. Patients registered from 2017 to 2023 at centers located in the southeast and northeast regions of Brazil, which account for more than two-thirds of the Brazilian population, were included. The Brazilian Health System has a unique composition, divided into Public Health Services (Public Services, historically underfunded, and available to all citizens and maintained by the Brazilian Government) and Complementary Health Services (Private Services, available to those with private health insurance either by their own or by the employer). Both were included. The primary outcome was progression-free survival (PFS), and secondary outcomes included overall survival (OS), relapse, and non-relapse mortality. Univariable analyses were conducted using Kaplan-Meier and cumulative incidence curves and compared with the log-rank and Gray tests, respectively. Because of the relatively low number of patients in the HGBL group, multivariable analysis was not performed. BRA-DLBCL was funded by AstraZeneca. Results We included 37 patients with HGBL and compared them with 532 patients with DLBCL. Unfortunately, FISH for BCL-2 and MYC rearrangements were not universally performed, and the diagnosis of HGBL was based solely on morphology. The median follow-up was 40 months. In the DLBCL group, the cell of origin was germinal center in 275 and non-germinal center in 257. Patients with HGBL were younger (median age, 51 vs 65 years), with a slight male predominance (68% vs 54%). Private Services accounted for most cases in HGBL (69%), compared with 40% of cases in DLBCL. B-symptoms were more frequent in the HGBL group (42% vs 28%), as well as primary treatment with R-DA-EPOCH (24% vs 7%). Other baseline patient characteristics were well balanced. Most patients had ECOG 0-1 (78%) and 69% were staged III-IV (not different between the groups). Three-year PFS was 59% for HGBL (95CI 45-77%) and 60% for DLBCL (95CI 55-64%, p=0.40). Three-year overall survival was non-significantly lower for HGBL (60%, 95CI 45-79%) compared with DLBCL (69%, 95CI 65-73%, p=0.20). Three-year relapse rates (30% for HGBL, 95CI 18-49%, and 30% for DLBCL, 95CI 27-35%, p=0.80) and three-year non-relapse mortalities (11% for HGBL, 95CI 4-27%, and 10% for DLBCL, 95CI 8-13%, p=0.52) were not different.Discussion In this multicenter study of over 500 Brazilian patients, we identified around 7% of HGBL based on morphology solely. We couldn't find any difference in outcomes, except for non-significantly worse overall survival, suggesting that, once relapsed, HGBL may be less responsive to subsequent therapy, compared with DLBCL. Moreover, intensive regimens were more common in the HGBL group. It came to our attention that most HGBL cases were reported by Private Services, suggesting that information bias may have played a role. More efforts are needed to correctly diagnose this new WHO category, as well as more studies to characterize prognosis and the best treatments.