Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6)

Hanno M. Witte*, Jörg Riedl, Axel Künstner, Anke Fähnrich, Julius Ketzer, Stephanie M.J. Fliedner, Niklas Reimer, Veronica Bernard, Nikolas von Bubnoff, Hartmut Merz, Hauke Busch, Alfred Feller, Niklas Gebauer

*Corresponding author for this work

Abstract

Background: There is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard. Objective: The present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with MYC and BCL2 rearrangements (prDLBCL/HGBL-MYC/BCL2) (n = 13) and HGBL, not otherwise specified (NOS), with MYC and BCL6 rearrangements (prHGBL, NOS-MYC/BCL6) (n = 6) based on our previously published whole-exome sequencing (WES) cohort. Patients and Methods: For genomic analysis, the institutional MTB WES pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed and supplemented by a comprehensive immunohistochemical work-up. Consecutive database research and annotation according to established evidence levels for molecularly stratified therapies was performed (NCT-DKTK/ESCAT). Results: Molecularly tailored treatment options with NCT-DKTK evidence level of at least m2A were identified in each case. We classified mutations in accordance with biomarker/treatment baskets and detected a heterogeneous spectrum of targetable alterations affecting immune evasion (IE; n = 30), B-cell targets (BCT; n = 26), DNA damage repair (DDR; n = 20), tyrosine kinases (TK; n = 13), cell cycle (CC; n = 7), PI3K-MTOR-AKT pathway (PAM; n = 2), RAF-MEK-ERK cascade (RME; n = 1), and others (OTH; n = 11). Conclusion: Our virtual MTB approach identified potential molecularly targeted treatment options alongside targetable genomic signatures for both prDLBCL/HGBL-MYC/BCL2 and prHGBL, NOS-MYC/BCL6. These results underline the potential of MTB consultations in difficult-to-treat lymphomas early in the treatment sequence.

Original languageEnglish
JournalTargeted Oncology
Volume18
Issue number5
Pages (from-to)749-765
Number of pages17
ISSN1776-2596
DOIs
Publication statusPublished - 09.2023

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)
  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)
  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 205-14 Haematology, Oncology
  • 204-05 Immunology

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