https://orcid.org/0000-0002-2365-5371
Key Points
Population-wide introduction of DA-EPOCH-R is associated with improved outcomes in HGBCL-DH-BCL2 with DLBCL morphology.
The most notable improvements in outcomes after DA-EPOCH-R introduction were observed in the IG::MYC and DZsig-positive subgroups.
High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) is associated with poor outcomes following standard chemoimmunotherapy, prompting dose-intensive regimen use. However, the benefit of intensification is unclear due to rarity precluding randomized trials, and selection bias in retrospective comparisons. In 2015, BC Cancer introduced a provincial guideline recommending dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for fit patients aged £75 years with HGBCL-DH-BCL2 identified by routine cytogenetic testing. To assess this guideline's impact, we compared the outcomes of patients with de novo HGBCL-DH-BCL2 tumors of diffuse large B-cell lymphoma (DLBCL) morphology across two eras. The DA-EPOCH-R era (2015-2020) included patients diagnosed after guideline implementation. The historic era (2005-2010) included patients identified from a historic province-wide cohort of patients with DLBCL morphology tumors that underwent universal cytogenetic testing in a research setting, predominantly treated with standard chemoimmunotherapy. Two-year overall survival (OS) was significantly improved in the DA-EPOCH-R versus historic era (75% versus 47%, P=.008) in HGBCL-DH-BCL2, whereas OS remained unchanged in DLBCL, not otherwise specified (NOS) (78% versus 76%, P=.17). Within HGBCL-DH-BCL2, tumors harboring immunoglobulin MYC partner loci (43%) and those expressing the dark-zone signature (77%) were associated with the most substantial survival improvements. In a contemporary cohort of HGBCL-DH-BCL2 histologically transformed from follicular lymphoma in the DA-EPOCH-R era, outcomes of chemoimmunotherapy-naïve patients were comparable to those with de novo disease, whereas patients treated with chemoimmunotherapy for follicular lymphoma prior to transformation had poor outcomes. These data support using DA-EPOCH-R in select patients with HGBCL-DH-BCL2 of DLBCL morphology.
