Treatment of DLBCL with MYC and BCL-2 Rearrangement (Double-Hit) or Dark Zone Gene-Expression Signature
Patients with diffuse large B-cell lymphoma who carry simultaneous MYC and BCL-2 rearrangements — termed double-hit lymphoma — or who are identified by a dark zone gene-expression signature represent a distinct, higher-risk subgroup. This molecular profile has direct implications for first-line treatment selection.
Clinical Scenario
This protocol applies to DLBCL patients with both a MYC rearrangement and a BCL-2 rearrangement (double-hit), or those identified by the dark zone gene-expression signature when molecular profiling is available. Standard-intensity first-line therapy is not the preferred approach in this group.
Treatment Approach
Current evidence supports escalation to a more intensive chemotherapy regimen rather than standard first-line DLBCL therapy. The full protocol specifies which intensive regimen is appropriate and under what conditions.
Complete regimen details — components, cycle structure, sequencing criteria — are available in the full structured protocol.
References
DOI: 10.1038/s41408-026-01458-2
- Those with Myc and BCL-2 rearrangements, as well as those identified by the "dark zone" signature (if this analysis can be performed), should receive a more intensive regimen such as DA-R-EPOCH for 6 cycles (Fig. 1).
- In these patients, administration of a more intensive regimen such as DA-R-EPOCH or CODOX-M/IVAC-R is preferred.
- These patients are commonly treated with more intensive regimens such as dose adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or Burkitt-like regimen like CODOX-M/R-IVAC (cyclophosphamide, doxorubicin, methotrexate, ifosfamide, etoposide, cytarabine and rituximab).
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