Oral Drug Demonstrates Favorable Benefit-Risk Profile in Non-Hodgkin Lymphoma

The results of a phase 2 trial of the investigational oral drug duvelisib shows promise in the treatment of indolent non-Hodgkin lymphoma.

The open-label, single-arm DYNAMO study examined the safety and efficacy of duvelisib in patients with follicular lymphoma (FL), small lymphocytic lymphoma (SLL), or marginal zone lymphoma, whose disease is double-refractory to rituximab (Rituxan) and chemotherapy or radioimmunotherapy.

Duvelisib is an oral, dual inhibitor designed to target the phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma enzymes, which are known to help promote cancer growth and survival.

For the study, 129 participants received 25 mg of duvelisib twice daily in 28-day cycles until disease progression or unacceptable toxicity.

The primary endpoint as assessed by the independent review committee was overall response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), time to response, adverse events (AEs), and changes in safety laboratory values.

The results of the study, published in Hematological Oncology, showed an ORR of 43% among patients with double refractory FL and 68% among patients with SLL. Thirty-three percent of patients with marginal zone lymphoma were responsive to treatment.

“We believe that oral duvelisib has the potential to be an important new treatment option for lymphoma patients,” investigator Pier Luigi Zinzani, MD, PhD, said in a press release. “What I find particularly encouraging are the responses we saw in patients with double-refractory disease, a population with few treatment options left. The data we are presenting at EHA [European Hematology Association] continue to demonstrate that duvelisib monotherapy can achieve meaningful and durable responses.”

Among the 36 patients with FL who responded to treatment, 1 had a complete response and 35 had partial responses. Responses occurred a median of 2 months after the start of treatment, of whom, 83% experienced a reduction in the size of their lymph nodes.

The median DoR was 7.9 months, median PFS was 8.3 months, and median OS was 27.8 months in patients with FL. The most common AEs were diarrhea, neutropenia, anemia, and thrombocytopenia, according to the release.

All 19 patients with double-refractory SLL who responded to duvelisib had partial responses. The median DoR was 10.1 months, median PFS was 11.7 months, and the median OS was 28.9 months. Most notably, 100% of evaluable patients with SLL who received duvelisib experienced a reduction in the size of their target lymph nodes, according to the report.

The most common AEs among SLL patients were neutropenia, thrombocytopenia, anemia, pneumonia, increases in alanine aminotransferase and aspartate aminotransferase, and diarrhea.

“The data from DYNAMO remain positive, and reporting the results from long-term follow-up is important for the medical community and for the overall development of duvelisib,” Hagop Youssoufian, MSc, MD, head of Hematology and Oncology Development at Verastem, said in a release. “Oral duvelisib monotherapy has demonstrated clinical activity across a number of hematologic cancers, including chronic lymphocytic leukemia, indolent non-Hodgkin lymphoma, and T-cell lymphoma. Based on the results we have seen thus far, we remain full committed to exploring duvelisib’s potential across a wide range of lymphoid malignancies.”

The findings were presented at the 22nd Congress of the EHA in Madrid, Spain, in June 2017.