EZH2 Mutation Status at Diagnosis is a Useful Biomarker to Guide First-Line Therapy in Follicular Lymphoma

EZH2 mutation status could be a useful biomarker to guide first-line therapy in follicular lymphoma (FL) and that ctDNA is a promising tool for identifying patients with this mutation, according to a study recently published in in BMC Cancer.

“EZH2 is mutated in nearly 25% of [FL] cases. Little is known about how EZH2 affects patients’ response to therapy,” wrote C. Martínez-Laperche, PhD, Gregorio Maranon Health Research Institute, Madrid, Spain and colleagues. “In this context, the aim of this study was to retrospectively analyze the frequency of mutations in EZH2 at diagnosis in tissue and ctDNA in patients with FL and to assess the patients’ outcomes after receiving immunochemotherapy, depending on the EZH2 mutation status.”

Among the 154 patients included in the study, 42 (27%) presented with mutated EZH2 at diagnosis. Patients were divided into 2 groups based on FL grade: high-grade FL (n = 13) and low-grade FL (n = 141). In the high-grade FL group 6 (46%) patients had mutated EZH2. In the low-grade group, 36 (26%) patients had mutated EZH2.

Among patients with available ctDNA at diagnosis, 44% of those with mutated EZH2 in tissue had the mutation in ctDNA. EZH2 mutations in ctDNA were not identified in any patients with unmutated EZH2 in tissue.

In the high-grade group, patients with mutated EZH2 had a statistically higher FLIPI risk than those with unmutated EZH2 (100% vs 0%; P = .048). However, no differences were noted in comparing clinical and biological characteristics and outcomes between mutated and unmutated patients. In the low-grade group, no statistically significant difference was noted in comparing clinical characteristic immunohistochemical and molecular markers between mutated and unmutated patients.

Researchers noted that all patients in the high-grade group were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In the low-grade group, 123 patients received treatment and 18 were observed with a watch and wait strategy. Of the patients treated, 30 received rituximab-bendamustine, 67 received R-CHOP, and 26 received rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), rituximab alone, or radiotherapy 

The study found that R-CHOP could be a more suitable regimen for mutated patients and rituximab-bendamustine a more suitable regimen for unmutated patients. Unmutated patients who received R-CHOP had significantly more relapses than patients who received rituximab-bendamustine (16 out of 49 vs 2 out of 23, P = .040). Furthermore, results show that patients with mutated EZH2 treated with R-CHOP vs those treated with rituximab-bendamustine present a lower incidence of relapse (10% vs 42%; P = .09 at 4 years), a higher PFS (92% vs 40%; P = .039 at 4 years), and higher OS (100% vs 78%; P = .039 at 4 years).

“In conclusion, our study shows that the status of the EZH2 mutation in FL at diagnosis could be a useful marker for the selection of first-line treatment in low-grade FL,” concluded Martínez-Laperche and colleagues. “Furthermore, ctDNA could be a promising tool in identifying mutated patients, especially in advanced stage and high-grade FL.”

Source:

Martínez-Laperche C, Sanz-Villanueva L, Díaz Crespo FJ, et al. EZH2 mutations at diagnosis in follicular lymphoma: a promising biomarker to guide frontline treatment. BMC Cancer. 2022;22(1). doi:10.1186/s12885-022-10070-z