Population-wide introduction of dose-adjusted EPOCH-R in high-grade B-cell lymphoma with MYC/BCL2 rearrangements, DLBCL morphology.

This study evaluated whether implementing a provincial guideline favoring DA‑EPOCH‑R for fit patients (≤75 years) with high‑grade B‑cell lymphoma with MYC and BCL2 “double‑hit” rearrangements and diffuse large B‑cell lymphoma (DLBCL) morphology improves outcomes compared with prior standard chemoimmunotherapy.

Design and cohorts:

• Two eras were compared in one provincial system:
  • Historic era (2005–2010): double‑hit cases identified from a research cohort with universal cytogenetic testing; treatment predominantly standard R‑CHOP–like chemoimmunotherapy.
  • DA‑EPOCH‑R era (2015–2020): double‑hit cases identified by routine cytogenetic testing after guideline implementation; recommended treatment DA‑EPOCH‑R for suitable patients.
• Analyses were restricted to de novo high‑grade B‑cell lymphoma with MYC/BCL2 rearrangements and DLBCL morphology. Outcomes of DLBCL, not otherwise specified (NOS), were used as a comparator.
• A separate contemporary cohort of histologic transformations from follicular lymphoma (FL) in the DA‑EPOCH‑R era was also evaluated.

Key findings:

• In de novo double‑hit disease with DLBCL morphology:
  • Two‑year overall survival improved from 47% in the historic era to 75% in the DA‑EPOCH‑R era (P = .008).
  • In contrast, 2‑year overall survival in DLBCL NOS was similar between eras (78% vs 76%, P = .17), arguing against a general era effect and supporting a regimen‑specific benefit in the double‑hit subgroup.
• Biologic subsets with the greatest apparent benefit:
  • Tumors with immunoglobulin MYC partner loci (about 43% of double‑hit cases).
  • Tumors expressing a dark‑zone–like gene expression signature (about 77% of cases).
• Transformed FL cohort in the DA‑EPOCH‑R era:
  • Patients who were chemoimmunotherapy‑naïve at the time of transformation had outcomes comparable to de novo double‑hit disease.
  • Patients previously treated with chemoimmunotherapy for FL before transformation had poor outcomes despite DA‑EPOCH‑R.

Clinical implications:

• Within the constraints of a nonrandomized, era‑based comparison, DA‑EPOCH‑R is associated with substantially improved survival for selected patients with double‑hit MYC/BCL2 high‑grade B‑cell lymphoma of DLBCL morphology.
• Benefit appears most pronounced in cases with IG‑MYC partners and dark‑zone biology.
• Prior chemoimmunotherapy exposure for FL before transformation may identify a subgroup with persistently poor prognosis despite intensive front‑line therapy, highlighting a need for alternative strategies.