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

Andreas Rosenwald, Susanne Bens, Ranjana Advani, Sharon Barrans, Christiane Copie-Bergman, Mad-Helenie Elsensohn, Yaso Natkunam, Maria Calaminici, Birgitta Sander, Maryse Baia, Alexandra Smith, Daniel Painter, Luu Pham, Shuchun Zhao, Marita Ziepert, Ekaterina S. Jordanova, Thierry J. Molina, Marie José Kersten, Eva Kimby, Wolfram KlapperJohn 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 Maucort-Boulch

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)3359-3368
JournalJournal of Clinical Oncology
Volume37
Issue number35
DOIs
Publication statusPublished - 2019

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