Search

Abstract Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis was used to identify a signature associated with high risk of early clinical failure independent of IPI and COO. Further analysis revealed the signature was associated with metabolic reprogramming and identified cases with a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. This novel and integrative approach is the first to identify a signature at diagnosis, in a real-world cohort of DLBCL, that identifies patients at high risk for early clinical failure and may have significant implications for design of therapeutic options.

Abstract Studies evaluating Positron Emission Tomography scan after 2 cycles of chemotherapy (PET2) in newly diagnosed diffuse large B cell lymphoma (DLBCL) are heterogeneous in patient characteristics, treatments and have conflicting results. Here we report association of PET2 with outcomes in two large independent prospective cohorts of newly diagnosed DLBCL pts treated with two RCHOP-based regimens. The discovery cohort consisted of pts enrolled in single arm phase 2 MC078E study of lenalidomide with RCHOP (R2CHOP). The validation cohort consisted of RCHOP-treated pts from the Molecular Epidemiology Resource (MER) cohort. Pts who received 3-6 cycles of therapy and had PET2 were included in the study. Patients who progressed on PET2 were excluded. Revised response criteria 2007 were used to define PET2 response PET2 positive (PET2 + ) pts had inferior EFS [24-month EFS 45.5% vs 87.9%, HR 4.0, CI95 (2.1–7.9), p

Abstract Immediate treatment for asymptomatic, low-tumor burden follicular lymphoma (FL) has not shown an overall survival benefit over “watch and wait” (W/W) strategy. We estimated incidence of treatment initiation at specific time points and assessed its association with the presence of any criteria such as GELF, BNLI, GITMO at diagnosis. FL patients managed by W/W strategy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE between 2002 and 2015. Cumulative incidence estimates of treatment initiation were calculated using transformation (as the first event) and death as competing risks. 401 FL patients were identified on W/W strategy. At a median follow-up of 8 years, 256 (64%) initiated treatment. For patients on the W/W strategy for 5 years, the likelihood of treatment initiation in the next 5 years was 12% compared to 43% at diagnosis unlike transformation rates which remained steady. Patients with any of popular treatment criteria at diagnosis did not have increased therapy initiation rates (44% vs. 42%) during the first 5 years or lymphoma-related death rates at 10 years (6% vs. 7%). Identifying biological differences in patients with early vs. late or no progression is a critical next step in understanding outcomes in W/W patients.