15-ICML: Identifying Genetic Alterations Associated With Relapse in DLBCL
In an abstract presented by Rushton et al at the 15th International Conference on Malignant Lymphoma (ICML; Abstract 004), researchers found that patients with diffuse large B-cell lymphoma (DLBCL) with specific mutations in relapse-enriched genes may be at a higher risk of treatment failure. The authors wrote that these mutations “may have power as biomarkers to identify patients at a high risk of relapse.”
Researchers collected samples from 134 patients with relapsed or refractory DLBCL enrolled in three clinical trials. Plasma samples were collected prior to and several times after treatment. Exome and target panel sequencing of lymphoma-associated genes was performed on cell-free DNA (from plasma samples and tissue biopsies [where available]).
Mutation prevalence was compared to a large unselected cohort of diagnostic DLBCL samples.
Study Findings
In relapsed or refractory DLBCL specifically, patients were enriched for mutations in 5 genes:
- TP53, which was previously associated with relapsed or refractory DLBCL
- IL4R, which researchers reported may lead to constitutively active JAK/STAT signaling and inferior overall survival
- HVCN1, which encodes a voltage-gated proton channel that modulates the B-cell receptor
- RB1
- MS4A1, which researchers reported encodes CD20, the target of the front-line DLBCL treatment rituximab. These mutations are predicted to either truncate CD20 or destabilize a transmembrane helix; 4 of 15 patients had a MS4A1 mutation that affected tyrosine 86.
Researchers also observed recurrent in-frame deletions targeting S1680 of CREBBP, but the functional effect of this deletion has not yet been characterized.
The researchers concluded, “[These mutations] may have power as biomarkers to identify patients at a high risk of relapse and could inform on the mechanism of acquired resistance to components of R-CHOP [rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone].”
Disclosure: For full disclosures of the study authors, visit lymphcon.ch.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
