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Chromatin Regulator Mutations: Novel Predictors of Adverse Outcomes in Multiple Myeloma?

By: Emily Rhode
Posted: Friday, October 28, 2022

Research that could further facilitate the development of prognostic evaluation methods for multiple myeloma based on gene mutations has been published in Clinical Epigenetics. Lijuan Chen, MD, of The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, China, and colleagues found that a high mutational load was linked to a poor prognosis in patients with multiple myeloma.

“Prognostic models based on gene mutations were commendably prognostic evaluation methods that could provide a reference for clinical practices,” the study authors said.

The researchers collected bone marrow samples from 147 untreated patients with newly diagnosed multiple myeloma to perform next-generation sequencing for mutation analysis. They identified 343 genetic mutations, with a median of 17. Patients with the IgD subtype had significantly more mutations than patients with the IgG (P = .0219) and IgA (P = .0363) subtypes. Mutational load was higher in patients with an International Staging System (ISS) rating of stage III than in patients with ISS stage I and II ratings (P = .0249). The team discovered that mutations in chromatin regulators that form the KMT2C/D COMPASS complex, including KMT2C (14.3%), KMT2D (14.3%), EP300 (11.6%), as well as the ARID gene family (31.3%), occurred frequently in patients with newly diagnosed multiple myeloma.

Patients were treated with proteasome inhibitors (50.3%), a combination of proteasome inhibitors and immunomodulatory drugs (38.1%), or immunomodulatory drugs alone (9.5%). The median follow-up time was 26 months, with a 3-year overall survival rate of 75.4%. Those with a high mutational load (number of mutations ≥ 20; n = 47) had significantly shorter progression-free survival than those with a low mutational load (median progression-free survival = 19.0 vs. 32 months; P = .0098) and a significantly shorter 3-year overall survival (66.1% vs. 80%; P = .0290).  

“Our findings emphasized the importance of [chromatin regulator] mutations in [newly diagnosed multiple myeloma] patients, and the mutations affecting [the KMT2C/D COMPASS complex] might promote the development of [multiple myeloma],” the researchers concluded.

Disclosure: The study authors reported no conflicts of interest.

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