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 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 Maucort-Boulch

doi:10.1200/JCO.19.00743

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

Health Sciences

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	JCO1900743
Journal	Journal of Clinical Oncology
Early online date	9 Sept 2019
DOIs	https://doi.org/10.1200/JCO.19.00743
Publication status	E-pub ahead of print - 9 Sept 2019

Bibliographical note

© 2019 American Society of Clinical Oncology. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

Please include [email protected] in any changes made / required for this entry

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10.1200/JCO.19.00743

jco.19.00743
© 2019 American Society of Clinical Oncology. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

Cite this

Rosenwald, A., Bens, S., Advani, R., Barrans, S., Copie-Bergman, C., Elsensohn, M.-H., Natkunam, Y., Calaminici, M., Sander, B., Baia, M., Smith, A., Painter, D., Pham, L., Zhao, S., Ziepert, M., Jordanova, E. S., Molina, T. J., Kersten, M. J., Kimby, E., ... Maucort-Boulch, D. (2019). Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium. Journal of Clinical Oncology, JCO1900743. Advance online publication. https://doi.org/10.1200/JCO.19.00743

@article{a1c189f2044d419f91416cf802586d9e,

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

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.",

author = "Andreas Rosenwald and Susanne Bens and Ranjana Advani and Sharon Barrans and Christiane Copie-Bergman and Mad-Helenie Elsensohn and Yaso Natkunam and Maria Calaminici and Birgitta Sander and Maryse Baia and Alexandra Smith and Daniel Painter and Luu Pham and Shuchun Zhao and Marita Ziepert and Jordanova, {Ekaterina S} and Molina, {Thierry J} and Kersten, {Marie Jos{\'e}} and Eva Kimby and Wolfram Klapper and John Raemaekers and Norbert Schmitz and Fabrice Jardin and Stevens, {Wendy B C} and Eva Hoster and Anton Hagenbeek and Gribben, {John G} and Reiner Siebert and Gascoyne, {Randy D} and Scott, {David W} and Philippe Gaulard and Gilles Salles and Catherine Burton and {de Jong}, Daphne and Sehn, {Laurie H} and Delphine Maucort-Boulch",

note = " {\textcopyright} 2019 American Society of Clinical Oncology. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher{\textquoteright}s self-archiving policy. Further copying may not be permitted; contact the publisher for details. Please include [email protected] in any changes made / required for this entry",

year = "2019",

month = sep,

day = "9",

doi = "10.1200/JCO.19.00743",

language = "English",

pages = "JCO1900743",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

}

Rosenwald, A, Bens, S, Advani, R, Barrans, S, Copie-Bergman, C, Elsensohn, M-H, Natkunam, Y, Calaminici, M, Sander, B, Baia, M, Smith, A , Painter, D, Pham, L, Zhao, S, Ziepert, M, Jordanova, ES, Molina, TJ, Kersten, MJ, Kimby, E, Klapper, W, Raemaekers, J, Schmitz, N, Jardin, F, Stevens, WBC, Hoster, E, Hagenbeek, A, Gribben, JG, Siebert, R, Gascoyne, RD, Scott, DW, Gaulard, P, Salles, G, Burton, C, de Jong, D, Sehn, LH & Maucort-Boulch, D 2019, 'Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium', Journal of Clinical Oncology, pp. JCO1900743. https://doi.org/10.1200/JCO.19.00743

TY - JOUR

T1 - Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma

T2 - 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

N1 - © 2019 American Society of Clinical Oncology. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. Please include [email protected] in any changes made / required for this entry

PY - 2019/9/9

Y1 - 2019/9/9

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.

U2 - 10.1200/JCO.19.00743

DO - 10.1200/JCO.19.00743

M3 - Article

C2 - 31498031

SN - 0732-183X

SP - JCO1900743

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

ER -