How safe and effective is abexinostat in patients with relapsed/refractory NHL?

This study investigated the effects of abexinostat in patients with relapsed or refractory (did not respond to treatment) NHL (non-Hodgkin’s lymphoma). The study concluded that abexinostat is safe and effective in patients with NHL (particularly follicular lymphoma and diffuse large B-cell lymphoma).

Histone deacetylase inhibitors (HDIs) interfere with the action of histone deacetylases (HDACs), important proteins that control gene expression in cells. Mutations in HDAC genes have been linked to cancer development. Because HDACs regulate many important functions that cells need to survive – like growth, blood vessel formation, and immunity – HDACs are considered promising targets for cancer therapy. 

Abexinostat is an HDI that has been shown to be effective in T-cell lymphomas (T-CL). Whether or not it is effective in B-cell lymphomas, such as follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), is not clear.

This study involved 100 patients with relapsed or refractory NHL or CLL. Of these, 84 patients had a subtype of NHL (including FL, DLBCL, T-CL, or mantle cell lymphoma) and 16 patients had CLL. All patients received abexinostat. Patients were followed for an average of 18 months.

Patients across all tumor types showed a 28% response rate (tumor shrinking or disappearance), with 5% of patients showing complete tumor disappearance. Three NHL subtypes showed the highest response rates: FL (56%), DLBCL (31%), and T-CL (40%). Progression-free survival (time from treatment until disease progression) was 10.2 months for FL, 2.8 months for DLBCL, and 5.5 months for T-CL. Average overall survival (time from treatment until death from any cause) was 17.8 months (T-CL) and 10.2 months (DLBCL), and was not reached for FL. 

82% of patients reported severe or life-threatening side effects, with low platelet count (80%, blood cells involved in clotting), low white blood cell count (27%), and low red blood cell count (12%) the most common. 21% of patients had reduced doses of abexinostat during the study, and 29% of patients stopped treatment due to side effects. 56% of patients stopped treatment due to progression of their disease.

The study concluded that abexinostat is safe and effective in patients with relapsed or refractory NHL (particularly FL, T-CL, and DLBCL).

This study was funded by Pharmacyclics, the company developing and testing abexinostat in clinical trials. Comparing the results of this study to other abexinostat clinical trials is difficult due to differences in dosage schedules, which can cause different rates of adverse events. The impact of less intense dosage schedules of abexinostat on FL, T-CL, and DLBCL needs further research.

If you have relapsed or refractory NHL, talk to your care team about HDIs like abexinostat.