Copanlisib shows promise in treatment of indolent or aggressive lymphoma
Intravenous copanlisib shows therapeutic potential in patients with various subtypes of indolent and aggressive malignant lymphoma, demonstrating manageable toxicity, according to the results of a phase II study.
The study population included 33 patients with indolent lymphoma and 51 with aggressive lymphoma. All patients received copanlisib administered intravenously on days 1, 8 and 15 of a 28-day cycle. Immunohistochemistry, gene-expression profiling and mutation analysis were performed using archival tumour tissues.
Of the patients, 48.5 percent had follicular lymphoma while 33.3 percent had peripheral T-cell lymphoma. Majority (78.6 percent) had received prior rituximab, with 54.8 percent being rituximab-refractory. Median duration of treatment was 23 weeks in the indolent group and 8 weeks in the aggressive group (overall range, 2–138). A total of 80 patients were evaluated for efficacy.
The objective response rate was 43.7 percent (14/32) in the indolent group and 27.1 percent (13/48) in the aggressive group, and the corresponding median duration of response was 390 days (range, 0 to 825) and 166 days (range, 0 to 786). Median progression-free survival was 294 days (range, 0 to 874) in the indolent group and 70 days (range, 0 to 897) in the aggressive group.
Commonly reported adverse events were hyperglycaemia (57.1 percent; grade ≥3, 23.8 percent), hypertension (54.8 percent; grade ≥3, 40.5 percent) and diarrhoea (40.5 percent; grade ≥3, 4.8 percent). All these events were generally manageable. Neutropenia occurred in 28.6 percent of patients (grade 4, 11.9 percent). Molecular analysis demonstrated enhanced antitumour activity in tumours with upregulated PI3K pathway gene expression.
The present data show that the pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor copanlisib, which has predominant activity against the α- and δ- isoforms, has potential therapeutic value with manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma, researchers said.
“Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell and mantle cell lymphomas are ongoing,” they added.