Drug therapy for double-hit lymphoma

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Double-hit lymphoma (DHL) is a rare type of aggressive B-cell lymphoma defined as a high-grade B-cell lymphoma (HGBCL) with the presence of MYC, BCL2 and/or BCL6 rearrangements. Patients usually present with rapidly progressive and advanced stage of disease and, commonly, with extranodal involvement. Typically, patients become refractory to standard R-CHOP, and more aggressive regimens such as DA-EPOCH-R, R-hyperCVAD or CODOX-R regimens are typically needed. MYC is considered an “undruggable” mutation. Recent evidence suggests that pathogenic mechanisms associated with MYC could be potential targets. In this review, we also discuss the role of hematopoietic stem cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell therapy in DHL. We also discuss the role of potential novel agents such as BCL2 inhibitors, checkpoint inhibitors, bromodomain and extraterminal (BET) family inhibitors, Pi3K inhibitors, and others.

Keywords: double-hit lymphoma, MYC, targeted therapy.

Citation: Phuoc V, Sandoval-Sus J, Chavez JC. Drug therapy for double-hit lymphoma. Drugs in Context 2019; 8: 2019-8-1. DOI: 10.7573/dic.2019-8-1

Contributions: All authors contributed equally to the preparation of this review. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: Dr Chavez reports support from Kite, Novartis, Genentech, and AstraZeneca, outside the submitted work. Drs Sandoval-Sus and Phuoc have nothing to disclose. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at https://www.drugsincontext.com/wp-content/uploads/2019/11/dic.2019-8-1-COI.pdf

Acknowledgments: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2019 Phuoc V, Sandoval-Sus J, Chavez JC. https://doi.org/10.7573/dic.2019-8-1. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2019 Phuoc V, Sandoval-Sus J, Chavez JC. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/drug-therapy-for-double-hit-lymphoma/

Correspondence: Julio C. Chavez MD, Department of Malignant Hematology, Moffitt Cancer Center, 12902 Magnolia Drive, FOB3-HEME, Tampa, FL 33612, USA. julio.c.chavez@moffitt.org

Provenance: invited; externally peer reviewed.

Submitted: 21 August 2019; Peer review comments to author: 16 September 2019; Revised manuscript received: 15 October 2019; Accepted: 17 October 2019; Publication date: 2 December 2019.

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