Duvesilib, a combination PI3Kδ/PI3Kγ inhibitor, outperformed ofatumumab head-to-head in the phase III DUO trial, according to results published in Blood, the official journal of the American Society of Hematology. The trial involved 319 patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who had failed on at least 2 therapies; one-third had received at least 3 treatments.

A phase III trial has found that some patients with hard-to-treat leukemia and lymphoma showed significant improvement and longer progression-free survival with duvelisib, a dual oral inhibitor by Verastem Oncology.

FDA approved duvesilib September 24, 2018, for the treatment of relapsed or refractory CLL/SLL after at least 2 prior therapies. The therapy will be marketed under the name Copiktra.

According to the study, duvelisib extended the progression-free survival from a median of 9.9 months on ofatumumab to 13.3 months. The study drug appeared to offer greater benefits to patients with high-risk genetic mutations and poorer prognoses.

“The way we treat patients with CLL is changing rapidly as we move from standard chemotherapy-based approaches to more targeted therapies,” said principal investigator Ian W. Flinn, MD, PhD, Director of the Lymphoma Research Program at Sarah Cannon Research Institute in Nashville. “Based on these data, duvelisib may offer a new treatment option for patients who otherwise may have limited options.”

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Researchers who performed subgroup analyses found duvelisib worked just as well as ofatumumab among the hardest-to-treat cases, including those patients with p17 deletion or p53 abnormalities, who have few available therapeutic options. Patients with these genetic mutations who took duvelisib had a 60% reduction in their risk of cancer progression or death compared with similar patients in the ofatumumab group. “These are patients in whom traditional chemotherapy doesn't work,” Flinn said.

The dual inhibitor first blocks 2 kinases that are known to aid the growth of malignant B cells, and then it disrupts the microenvironment that supports tumor growth. “This dual inhibitory action is likely what makes duvelisib effective for patients with CLL or SLL,” Flinn said.

Patients in the study were followed for a median of 22.4 months. Overall response rate was higher in the duvelisib group (74% vs 45% in the ofatumumab group). Median treatment length was 50 weeks for the duvelisib group compared with 23 weeks for those receiving ofatumumab.

The most common adverse events were diarrhea, nausea, pyrexia, neutropenia, anemia, and cough in the duvelisib group and neutropenia and infusion reactions in the ofatumumab arm.

Most people taking duvelisib (78%) also had meaningful reductions in their lymph nodes compared with 16% of patients receiving ofatumumab. Swollen lymph nodes in the neck, arms, and abdomen can lead to limited mobility and increased discomfort.

According to the National Cancer Institute, more than 20,000 new cases of CLL are diagnosed in the US every year, with 4600 related deaths occurring annually.

Reference

Flinn W, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib versus ofatumumab in relapsed and refractory CLL/SLL [published online October 4, 2018]. Blood. doi: 10.1182/blood-2018-05-850461.