Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium | Zendy

Andreas Rosenwald | Zendy; Susanne Bens | Zendy; Ranjana H. Advani | Zendy; Sharon Barrans | Zendy; Christiane CopieBergman | Zendy; MadHélénie Elsensohn | Zendy; Yasodha Natkunam | Zendy; Maria Calaminici | Zendy; Birgitta Sander | Zendy; Maryse Baia | Zendy; Alexandra Smith | Zendy; Daniel Painter | Zendy; Luu Q. Pham | Zendy; Shuchun Zhao | Zendy; Marita Ziepert | Zendy; Ekaterina S. Jordanova | Zendy; Thierry Jo Molina | Zendy; Marie José Kersten | Zendy; Eva Kimby | Zendy; Wolfram Klapper | Zendy; John Raemaekers | Zendy; Norbert Schmitz | Zendy; Fabrice Jardin | Zendy; Wendy B.C. Stevens | Zendy; Eva Hoster | Zendy; Anton Hagenbeek | Zendy; John G. Gribben | Zendy; Reiner Siebert | Zendy; Randy D. Gascoyne | Zendy; David W. Scott | Zendy; Philippe Gaulard | Zendy; Gilles Salles | Zendy; Catherine Burton | Zendy; Daphne de Jong | Zendy; Laurie H. Sehn | Zendy; Delphine MaucortBoulch | Zendy

Open Access

Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium

Author(s) -

Andreas Rosenwald,

Susanne Bens,

Ranjana H. Advani,

Sharon Barrans,

Christiane CopieBergman,

MadHélénie Elsensohn,

Yasodha Natkunam,

Maria Calaminici,

Birgitta Sander,

Maryse Baia,

Alexandra Smith,

Daniel Painter,

Luu Q. Pham,

Shuchun Zhao,

Marita Ziepert,

Ekaterina S. Jordanova,

Thierry Jo Molina,

Marie José Kersten,

Eva Kimby,

Wolfram Klapper,

John Raemaekers,

Norbert Schmitz,

Fabrice Jardin,

Wendy B.C. Stevens,

Eva Hoster,

Anton Hagenbeek,

John G. Gribben,

Reiner Siebert,

Randy D. Gascoyne,

David W. Scott,

Philippe Gaulard,

Gilles Salles,

Catherine Burton,

Daphne de Jong,

Laurie H. Sehn,

Delphine MaucortBoulch

Publication year - 2019

Publication title -

journal of clinical oncology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 10.482

H-Index - 548

eISSN - 1527-7755

pISSN - 0732-183X

DOI - 10.1200/jco.19.00743

Subject(s) - bcl6 , medicine , diffuse large b cell lymphoma , hazard ratio , lymphoma , oncology , fluorescence in situ hybridization , rituximab , cyclophosphamide , context (archaeology) , biomarker , biopsy , vincristine , cancer research , pathology , antibody , chemotherapy , immunology , b cell , gene , biology , confidence interval , germinal center , biochemistry , paleontology , chromosome

PURPOSE MYC rearrangement ( MYC-R) occurs in approximately 10% of diffuse large B-cell lymphomas (DLBCLs) and has been associated with poor prognosis in many studies. The impact of MYC-R on prognosis may be influenced by the MYC partner gene (immunoglobulin [IG] or a non-IG gene). We evaluated a large cohort of patients through the Lunenburg Lymphoma Biomarker Consortium to validate the prognostic significance of MYC-R (single-, double-, and triple-hit status) in DLBCL within the context of the MYC partner gene.METHODS The study cohort included patients with histologically confirmed DLBCL morphology derived from large prospective trials and patient registries in Europe and North America who were uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or the like. Fluorescence in situ hybridization for the MYC, BCL2, BCL6, and IG heavy and light chain loci was used, and results were correlated with clinical outcomes.RESULTS A total of 5,117 patients were identified of whom 2,383 (47%) had biopsy material available to assess for MYC-R. MYC-R was present in 264 (11%) of 2,383 patients and was associated with a significantly shorter progression-free and overall survival, with a strong time-dependent effect within the first 24 months after diagnosis. The adverse prognostic impact of MYC-R was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner (hazard ratio, 2.4; 95% CI, 1.6 to 3.6; P < .001).CONCLUSION The negative prognostic impact of MYC-R in DLBCL is largely observed in patients with MYC double hit/triple-hit disease in which MYC is translocated to an IG partner, and this effect is restricted to the first 2 years after diagnosis. Our results suggest that diagnostic strategies should be adopted to identify this high-risk cohort, and risk-adjusted therapeutic approaches should be refined further.

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