In a nutshell
This study aimed to investigate the safety and effectiveness of ublituximab, umbralisib and ibrutinib combination in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL).
This study concluded that this combination appears safe and effective for these patients.
Patients with CLL and NHL are often treated with targeted therapies. Ublituximab and umbralisib are new targeted therapies and are being used in clinical trials. Ibrutinib (Imbruvica) is another targeted therapy. It has been approved and is commonly used to treat patients with CLL. Some patients with CLL or NHL do not respond to standard therapies or relapse after treatment. It is important to evaluate new treatment combinations for these patients.
It is not known if the combination of ublituximab, umbralisib and ibrutinib (UUI) would be safe and effective for treating patients with CLL and NHL.
Methods & findings
This study involved 46 patients with CLL or relapsed/refractory NHL. They were treated with UUI combination. 24 patients received treatment in 28-day cycles. They received progressive doses of umbralisib (400, 600 and 800mg) and fixed doses of ublituximab (900mg) and ibrutinib (420mg for CLL and 560mg for NHL). They received treatment until disease progression or intolerance. 22 patients then received the recommended dose of the drug combination that was calculated from the previous phase of the study. The average treatment duration was 16 months.
The recommended dose from the first phase was umbralisib 800 mg orally once daily plus ibrutinib orally once daily and intravenous ublituximab 900 mg administered on days 1, 8, and 15 of cycle 1, day 1 of cycles 2–6, and on day 1 of cycles 9 and 12. 37 of 44 patients (84%) achieved an overall response. Response to treatment lasted for an average of 21.8 months. Survival without cancer growing or spreading was 38.2 months, on average.
The most common side effects were diarrhea in 59%, fatigue in 50%, and infusion-related reaction in 43% of patients. Dizziness and nausea were also reported in 37% of patients, and cough in 35%. The most common severe and life-threatening side effects included low white blood cell count (22%) and cellulitis (bacterial infection in skin) in 13% of patients.
The bottom line
This study concluded that the UUI combination appears safe and effective in patients with CLL or NHL.
The fine print
This was only a phase I study (the first study of its kind). It included a small number of patients and short follow-up. Further studies are needed to fully understand this treatment combination.
Published By :
The Lancet. Haematology
Feb 01, 2019