Real-World Applications of Guideline Based Diagnostic and Treatment Patterns for Diffuse Large B-Cell Lymphoma within the Veterans Health Administration (VHA)

INTRODUCTION:

High grade lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (HGL) occur in less than 10% of DLBCL. While clinical trials demonstrated poor outcomes following standard rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) therapy for HGL since the early 2000s, the World Health Organization (WHO) identified this as a new category in 2016. There was a lack of consensus for FISH testing until NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) (V.1.2020) moved Karyotype/FISH testing for MYC from “USEFUL UNDER CERTAIN CIRCUMSTANCES” to “ESSENTIAL”. NCCN Guidelines^® V.1.2018 recognizes the lack of standard of care for HGL and comments about using dose-adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) DA-EPOCH-R for this category. The VHA is the largest integrated, uniform care access system in the United States. The objective of this study is to understand the real-world applications of NCCN Guidelines on testing and treatment patterns in DLBCL within VHA.

METHODS:

6266 patients were randomly selected for this retrospective chart review with an ICD code for DLBCL managed in the VHA from 01/01/2011 to 12/31/2021. This 11-year period is divided into three blocks: 2011-2015, 2016-2019 and 2020-2021, which represent pre-identification of HGL based on WHO classification, post-identification of HGL based on 2016 WHO classification Lymphoid neoplasm classification, and the change in MYC testing NCCN Guidelines (Version 1.2020), respectively. VHA is divided into five geographic regions, which includes the Pacific, Continental, Midwest, Southeast, and North Atlantic. Data abstractors collected baseline patient and disease characteristics, both manually and electronically, including but not limited to, testing and treatment patterns for those with a diagnosis of DLBCL in each time frame. Statistical comparisons were done using the Chi-Squared test.

RESULTS:

3178 met our inclusion criteria for DLBCL. Of the total patients, 1471 (46.3%) had FISH testing performed. Table 1 shows baseline characteristics. Of the patients tested, 97% of the patients were male, 75% were non-Hispanic white and median age was 68 years. The median Charlson Comorbidity Index (CCI) was 2. FISH testing rates increased over time from 28% in the first study period to 76% during the last study period. There was no statistically significant racial difference in FISH testing rates. Continental VHA district patients were less likely to have FISH testing completed when compared to other districts (p<0.0001). Despite an overall increase in FISH testing, as well as a change in testing NCCN Guidelines (Version 1.2020) there was no significant increase in the real-world utilization rate of DA-EPOCH-R for HGL during the different study periods (Figure 2).

CONCLUSION:

This is one of the largest retrospective studies reporting FISH testing and treatment patterns based on NCCN Guidelines for HGL. Despite significant improvement in the rates of FISH testing during our study period, there are significant regional differences, and 25% of the patents did not undergo FISH testing after the recommendation change in 2020. Our data also highlights the underutilization of DA-EPOCH-R in HGL patients within VHA. This may be attributed to knowledge gaps, diagnosis at older age, higher Charlson score due to multiple comorbidities, and regimen feasibility. Limitations of this study include a predominantly older, male population with equal health care access that may limit generalizability of our findings to the non-Veteran population. Data from our study underscores a need for increased awareness of NCCN Guidelines recommendations both in terms of testing and treatment planning outside the clinical trial setting.