Comparative Analysis of Clinical Characteristics and Outcomes of Large B Cell Lymphomas in US Veterans Health Administration (VHA) Based on FISH Rearrangement Patterns
Authors: Parekh Jay , Kaur Supreet , Franklin Kathleen , Mader Michael , Nooruddin Zohra 
Published: December 2024

Background: Outcomes of large B cell lymphoma are heterogenous and are impacted by several factors including MYC rearrangement. MYC rearrangement, along with BCL2 and/or BCL6, is known to negatively affect prognosis, although isolated MYC rearrangement negatively impacts advanced stage (PMID: 38177113). Understanding the associations of these rearrangements with patient demographics, clinical characteristics, response and survival outcomes is crucial. This study aims to provide a comprehensive analysis of the differences between patients with and without MYC rearrangement.
Methods: We performed a retrospective chart review of 3178 randomly selected large B cell lymphoma patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021, and for this study included patients with data available on FISH rearrangement. Patients with Primary CNS lymphoma were excluded. The cohort was divided into two groups: MYC not rearranged, and MYC rearranged. The MYC rearranged group was further divided into those with additional rearrangements: MYC with only BCL2 rearranged, MYC with only BCL6 rearranged, and MYC with BCL2 and BCL6 rearranged. Various parameters including age, sex, race/ethnicity, ECOG performance status, IPI risk, cell of origin, extranodal involvement, disease stage, LDH levels, CNS prophylaxis, treatment regimens, response to first-line treatment, and survival outcomes were analyzed.
Results: Out of the 3178 patients, 1,461 patients were included because FISH data was available. 1,226 (84%) had no MYC rearrangement, and 235 (16%) had MYC rearrangement. Median age at diagnosis was 68 years, 97% were males, 74% white race. Among those with MYC rearrangement, 72 (31%) patients had isolated MYC rearrangement, 100 (43%) had MYC with BCL2 rearranged, 27 (11%) had MYC with BCL6 rearranged, and 36 (15%) had MYC with rearrangements in both BCL2 and BCL6. The age, sex, race, stage and ECOG status were similar between MYC rearranged and non-rearranged groups. MYC rearranged patients had a higher IPI score with 57% patients having intermediate or higher score compared to 49% among those without rearrangement (p = 0.004). MYC rearranged patients were more likely to have a Germinal Center B cell of origin 67% vs 50%, (p&lt;0.0001). MYC rearranged patients were also more likely to have extranodal involvement in at least 2 sites, 32% vs 23%, (p=0.004) and have an elevated LDH, 63% vs 55%, (p=0.005). CNS prophylaxis was used more frequently in MYC rearranged patients, 29% vs 15%, (p&lt;0.0001). The vast majority of CNS prophylaxis in either group, when given, was intrathecal. MYC rearranged patients were more likely to receive DA-EPOCH-R, except those with isolated MYC rearrangement. Treatment regimens varied, with CHOP-based regimens less common in MYC rearranged patients compared to MYC non-rearranged patients, 40% vs 72%, (p&lt;0.0001). MYC rearranged patients had a lower complete response rate to first-line treatment, 54% vs 64%, and a higher rate of progressive disease or death, 23% vs 16%, (p=0.02).
MYC rearranged patients had 12-month and 24-month survival rates of 67% and 57%, respectively, compared to 79% and 69% in MYC non-rearranged patients, with a median overall survival (mOS) for MYC rearranged patients of 40.3 months (95% CI: 26.1 - 61.3) versus 72.9 months (95% CI: 66.4 - 84.3) for MYC non-rearranged patients (p=0.0003). There was no statistically significant difference in mOS when using CHOP-based (65 months) vs EPOCH (52 months) in MYC rearranged patients (p = 0.73).
Conclusion: To the best of our knowledge, this is one of the largest study reporting survival data on large B cell lymphoma patients with MYC rearrangement within the VHA. MYC rearrangement in patients is associated with statistically significant higher IPI risk scores, more frequent extranodal involvement, reduced response to first-line treatment and worse survival outcomes compared to those without MYC rearrangement, irrespective of regimen used. This indicates a need for more precise tools to define subtypes of MYC-R lymphoma and enhanced treatment approaches for improved outcomes.