P1168: CHARACTERISTICS PREDICTIVE OF PROGRESSION DURING FRONTLINE TREATMENT IN AGGRESSIVE B-CELL LYMPHOMAS

Abstract

Background: Primary refractory diffuse large B-cell lymphoma (DLBCL) represents 10-15% of DLBCL cases. The subgroup of refractory patients who have no response or progressive disease (PD) by the end of frontline treatment (EOT) is a high-risk group with particularly poor outcomes. It is challenging to identify such patients at diagnosis. Aims: To identify clinical, pathological, and cytogenetic characteristics of patients with progression during frontline treatment. Methods: Adult patients with newly diagnosed DLBCL, including patients with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (DHL/THL), between 2002 and 2019 and seen at Mayo Clinic Rochester were identified from the prospective Molecular Epidemiology Resource (MER) cohort study of the University of Iowa/Mayo Clinic Lymphoma SPORE. We analyzed patients who had no response or PD during treatment or by EOT (early PD group) and compared to non-early PD (non-ePD) patients (including relapsed patients). We compared demographics, clinical characteristics, cell of origin (COO), and MYC rearrangements using Chi-square analysis. Results: Out of 1,505 patients with DLBCL, there were 66 patients (4.3%) with early PD (N=20 PD/stable disease at interim PET-CT, N=46 PD by EOT). At baseline, 61% were male and the median age was 60. Early PD patients had more advanced stage III-IV (72.7% vs 53.3%), elevated serum lactate dehydrogenase (LDH) (64.0% vs 47.3%), >1 extranodal site involved (36.4% vs 23.3%), and International Prognostic Index (IPI) ≥3 (52.0% vs 33.6%)(all p <0.05 compared to non-ePD). COO distribution was similar between early PD and non-ePD patients. Among patients with complete pathological and cytogenetic data available (early PD, n=47; non-ePD, n=813), DHL or THL was observed in 23.4% of early PD patients compared to 9.2% in non-ePD patients (p=0.001). Of the DHL patients in the early PD group (n=8), MYC/BCL2 rearrangement was present in 87.5%, MYC/BCL6 in 12.5%. Dual Myc/Bcl2 expressor (DEL) was present in 42.2% of early PD patients (n=45) compared to 25.5% in non-ePD patients (n=736)(p=0.013). First-line treatment regimens in the early PD group included R-CHOP (74.2%), R-EPOCH (7.6%), and other immunochemotherapy (IC)(18.2%), which was similar to non-ePD patients. Summary/Conclusion: High-risk characteristics including DHL/THL and DEL are significantly associated with progressive disease during frontline treatment, suggesting that MYC-signaling may mediate chemoresistance. Known high-risk clinical features including advanced stage, elevated LDH, >1 extranodal site, and IPI ≥3 are also associated with early PD. Early identification of patients at high risk for early PD through clinical, pathological, and cytogenetic features is of utmost importance given the availability of clinical trials incorporating novel therapies in both frontline and consolidative approaches.