DYNAMO: Duvelisib in Refractory Indolent Non-Hodgkin Lymphoma
In the phase II DYNAMO trial reported in the Journal of Clinical Oncology, Flinn et al found a response rate of nearly 50% with duvelisib, an oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-γ and -δ, in indolent non-Hodgkin lymphoma refractory to rituximab and either chemotherapy or radioimmunotherapy.
Study Details
The multicenter trial included 129 patients with measureable disease, including 83 with follicular lymphoma, 28 with small lymphocytic lymphoma, and 18 with marginal zone B-cell lymphoma. Patients were treated with duvelisib 25 mg twice daily in 28-day cycles until progression, unacceptable toxicity, or death. Patients had a median age of 65 years and had received a median of three prior lines of therapy.
The primary endpoint was overall response rate assessed by independent review committee using the revised International Working Group criteria for malignant lymphoma.
Response Rates
The overall response rate was 47.3% (two patients experienced complete response), including response rates of 67.9% in small lymphocytic lymphoma, 42.2% in follicular lymphoma, and 38.9% in marginal zone B-cell lymphoma. Stable disease was observed in an additional 32.6% of patients. Median time to response was 1.7 months, and median duration of response was 10 months. Median progression-free survival was 9.5 months, with a 6-month rate of 62%. Median overall survival was 28.9 months, with a 1-year rate of 77%.
Adverse Events
The most common adverse events of any grade were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Grade ≥ 3 adverse events occurred in 88.4% of patients, with the most common being neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). Adverse events led to discontinuation of treatment in 31%, with the most common cause being pneumonitis (3.1%).
The investigators concluded, [In the study], oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory [indolent non-Hodgkin lymphoma], consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.”
Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Infinity Pharmaceuticals and Verastem Oncology. The study authors' full disclosures can be found at jco.ascopubs.org.
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