TY - JOUR
T1 - Prognostic significance of MYC rearrangement and translocation partner in diffuse large B-cell lymphoma: A study by the Lunenburg Lymphoma Biomarker Consortium
AU - Rosenwald, Andreas
AU - Bens, Susanne
AU - Advani, Ranjana
AU - Barrans, Sharon
AU - Copie-Bergman, Christiane
AU - Elsensohn, Mad-Helenie
AU - Natkunam, Yaso
AU - Calaminici, Maria
AU - Sander, Birgitta
AU - Baia, Maryse
AU - Smith, Alexandra
AU - Painter, Daniel
AU - Pham, Luu
AU - Zhao, Shuchun
AU - Ziepert, Marita
AU - Jordanova, Ekaterina S.
AU - Molina, Thierry J.
AU - Kersten, Marie José
AU - Kimby, Eva
AU - Klapper, Wolfram
AU - Raemaekers, John
AU - Schmitz, Norbert
AU - Jardin, Fabrice
AU - Stevens, Wendy B. C.
AU - Hoster, Eva
AU - Hagenbeek, Anton
AU - Gribben, John G.
AU - Siebert, Reiner
AU - Gascoyne, Randy D.
AU - Scott, David W.
AU - Gaulard, Philippe
AU - Salles, Gilles
AU - Burton, Catherine
AU - de Jong, Daphne
AU - Sehn, Laurie H.
AU - Maucort-Boulch, Delphine
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85076329261&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31498031
U2 - https://doi.org/10.1200/JCO.19.00743
DO - https://doi.org/10.1200/JCO.19.00743
M3 - Article
C2 - 31498031
SN - 0732-183X
VL - 37
SP - 3359
EP - 3368
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 35
ER -