Despite the effective treatment options available to CLL patients, the disease may develop a resistance to prior therapies. When this happens, relapse or refractory disease becomes the result. Due to possible treatment resistance, there is a need for the continued development of tolerable medicines, particularly for high-risk patients. 

The Phase III DUO Trial

Duvelisib is a dual inhibitor that can be used as a stand-alone treatment. It directly targets cancerous B cells and tumor signaling pathways. In the Phase III DUO trial, duvelisib showed superior effectiveness to ofatumumab. During this trial, the patients that had disease progression (DP) while being treated with ofatumumab could cross over and receive duvelisib in an extension study. Switching to dubelisib resulted in favorable outcomes with manageable side effects. 

In the study, patients received a dose of 25mg, twice daily in a 28-day cycle (up to 11 cycles). Patients who were eligible for the study had disease progression and had tried at least 2 previous treatments. 

More Information About the Study Participants:

• 99 patients were initially enrolled
• They received duvelisib or ofatumumab within 3 months of disease progression
• 90 patients crossed over from ofatumumab to regular duvelisib dosing
• 63% were male with a median age of 68
• The median time from the initial diagnosis was 7.1 years
• The median number of previous therapies received by participants was three. “​​Most patients previously received a monoclonal antibody (100%), an alkylating agent (96%), or purine analog (73%). No patients received prior ibrutinib, idelalisib, or venetoclax” (AACR Journals).

Study Results

Response rates were studied only for patients who did not respond to ofatumumab and crossed over to duvelisib treatment. The overall response rate (ORR) with duvelisib was 77% and the median time to respond to this drug was 2.6 months. At follow-up, 88% of patients were progression-free at 6 months and 64% at 12 months. 

All patients in the DUO study underwent follow-up at the 6-year mark. At this time, patients who received duvelisib had a median overall survival (OS) of 43 months. The most common side effects of duvelisib were: diarrhea, fever, rash, colitis, and pneumonia. 

“In this study, duvelisib demonstrated effectiveness in patients who had received ≥1 prior therapy before being enrolled in the DUO trial and had then progressed after ofatumumab therapy." Study evidence shows that duvelisib is effective and tolerable for high-risk patients. The completion of this study occurred in June 2020.

Overall, based on all the data that is available for duvelisib, this medicine has shown to have a positive benefit/risk balance in relapsed/refractory CLL. Currently, according to the NCCN guidelines for CLL, duvelisib is recommended for those who have CLL that has progressed to third-line therapy. As a result of this therapy, many patients are now benefitting from duvelisib, which may serve as a bridge to other therapies.