Front‐line risk‐adapted therapy presented favorable outcomes for young patients with diffuse large b‐cell lymphoma: results from a consecutive cohort in china

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Young patients with high-risk diseases treated with standard chemotherapy have poor outcomes, and the optimal therapy has not been established yet. Aims: To improve the outcome of young DLBCL patients with clinically or biologically high-risk features by a risk-adapted treatment paradigm. Methods: Patients with untreated DLBCL from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199) were prospectively included in the protocol from April 2012 to April 2021. Patients in high-risk (HR) group (aaIPI ≥2) were assigned to receive intensive immunochemotherapy (IIC) (mainly DA-EPOCH-R). Patients in the low-risk (LR) (aaIPI <2) group were usually administered R-CHOP, while those diagnosed with biological high-risk (bio-HR) features including double/triple hit (DH/TH), double-expressor lymphoma (DEL), 17p/TP53 deletion, or CD5 positivity (CD5+) were also treated with IIC. Results: Three hundred and ten cases were included in this study, with 128 in the HR group and 182 in the LR group, respectively. The median age for all patients was 49 years (range, 14 to 65 years). The baseline clinicopathological characteristics of all patients are summarized in Table 1: 51.6% were male, 58.7% had stage III/IV diseases, 45.3% had elevated LDH, 62.0% had extranodal involvement and 56.1% had non-germinal center B-cell like (non-GCB) subtype disease. Regarding the bio-HR features, more patients in the HR group had DEL (39.8% vs. 20.1%), MYC-R (20% vs. 9.8%), and DH/TH status (10.6% vs. 5.2%) compared to those in the LR group. The median number of chemotherapy cycles was six (2–8 cycles). The end-of-treatment response was assessable in 308 patients who received at least two cycles of treatment. The overall response rate (ORR) of all patients was 91.3%, and 252 (79.9%) patients had CR or CRu. With a median follow-up of 42.8 months, the estimated 5-year progression-free survival (PFS) and overall survival (OS) rates for the entire cohort were 75.1% and 84.4%, respectively. Patients in the HR group achieved a 5-year PFS of 63.5% and OS of 73.5%, and frontline ASCT had a positive impact among patients in remission (p = 0.024 for PFS). The outcome was excellent for patients in the LR group with 5-year PFS and OS rates at 83.7% and 92.2%. In both HR and LR groups, no difference in survival was observed for patients with at least one of these features versus those without, indicating bio-HR features could be partly overcome by IIC. However, DH/TH and 17p/TP53 deletion were still associated with a poorer OS in the HR group (p = 0.004 and 0.014). Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies No conflicts of interests pertinent to the abstract.