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Genomic Alterations and MYD88MUT Variant Mapping in Patients with Diffuse Large B-Cell Lymphoma and Response to
Shiyu Jiang1, Yan Qin1, Lin Gui1
1Department of Medical Oncology, Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
Insights
This study investigated MYD88 mutations in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and their impact on ibrutinib response. Four of nine patients with MYD88 mutations responded to ibrutinib-containing treatment.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy with a significant relapse rate after front-line therapy.
- Relapsed or refractory (r/r) DLBCL presents a treatment challenge, with ibrutinib being a therapeutic option.
- Previous reports suggest MYD88 mutations (MYD88MUT) may influence ibrutinib response in r/r DLBCL.
Observation:
- This study analyzed 212 DLBCL patient samples, focusing on 60 patients with MYD88 mutations.
- Seven MYD88 variants were identified, with L265P being the most common (65.0%).
- Co-mutations in genes such as PIM1, IGH, CD79B, KMT2D, and TP53 were frequently observed alongside MYD88 mutations.
Findings:
- MYD88MUT L265P showed a higher incidence in patients with central nervous system involvement.
- Four out of nine MYD88MUT patients achieved response to ibrutinib-containing treatment.
- Response to ibrutinib was observed in patients with MYD88MUT/CD79BWT genotype.
Implications:
- This research provides valuable clinical data on MYD88 mutations in r/r DLBCL.
- Understanding MYD88 mutation status may help predict ibrutinib efficacy in DLBCL patients.
- Further research into MYD88's role can refine treatment strategies for refractory DLBCL.
Background:
Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy. Following front-line immunochemotherapy, 30-40% of DLBCL patients develop relapsed or refractory (r/r) disease, which can be treated with ibrutinib. It has been previously reported that MYD88MUT affects the response to ibrutinib in patients with r/r DLBCL.
Objective:
Here, we aimed to gather understanding of MYD88MUT in r/r DLBCL patients and to evaluate its influence on response to ibrutinib.
Patients And Methods:
In this study, tissue samples from DLBCL patients (n = 212) were retrospectively collected and sequenced by target-capturing panels of either 413 or 112 genes that are frequently mutated in non-Hodgkin's lymphoma. Sixty patients with MYD88 mutations and available clinical information were included for further analysis.
Results:
Seven MYD88MUT variants were identified, L265P (65.0%, n = 39), S219C (13.3%, n = 8), S243N (8.3%, n = 5), P258L (6.7%, n = 4), F283V (1.7%, n = 1), P141R (1.7%, n = 1), and V217F (1.7%, n = 1). One patient had MYD88 amplification. In addition, mutations in PIM1 (67%, n = 40), IGH fusion (48%, n = 29), CD79B (43%, n = 26), KMT2D (30%, n = 18), and TP53 (27%, n = 17) were identified. For patients with L265P, IRF4 (p = 0.011) was frequently mutated. Otherwise, TET2 (p = 0.016), NOTCH2 (p = 0.044), MET (p = 0.037), SOCS1 (p = 0.011), TNFRSF14 (p = 0.011), EZH2 (p = 0.037), and BCL6 (p < 0.001) mutations were associated with MYD88MUT non-L265P variants. The incidence rate of MYD88MUT L265P was significantly higher with central nervous system involvement (p = 0.034). Four out of nine MYD88MUT patients responded to ibrutinib containing treatment, and this included those with MYD88MUT/CD79BWT.
Conclusions:
This study adds clinical observations with MYD88MUT patients, further helping to understand the genetic features and possible correlation of MYD88MUT with response to ibrutinib.
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