Can idelalisib interruption and dose reduction improve clinical outcomes in patients with relapsed/refractory B-cell lymphoma/leukemia?

This study evaluated the impact of idelalisib (Zydelig) interruption or dose reductions on clinical outcomes in patients with relapsed/refractory (r/r) indolent (painless) non-Hodgkin lymphoma (iNHL) and chronic lymphocytic leukemia (CLL). This study showed that stopping idelalisib and reducing the dose due to side effects was associated with improved outcomes in these patients. 

B cells are a type of cell of the immune system. Some lymphomas and leukemias such as NHL and CLL disturb these cells. Targeted therapies such as rituximab (Rituxan) have improved outcomes of patients with B-cell blood cancers. However, many patients do not respond to treatment or develop painful side effects. Therefore, newer agents are needed for these patients.

Idelalisib is a targeted therapy approved to treat iNHL and CLL. It targets specific proteins on cancer cells, stopping them from growing. Side-effects caused by idelalisib have been reported, potentially limiting its efficacy. It remains unknown if stopping treatment and/or reducing dosage might improve its effectiveness.

This study analyzed data from 125 patients with r/r iNHL and 283 patients with r/r CLL. All patients received treatment with idelalisib. Clinical outcomes of patients who experienced side effects and their treatment was stopped were evaluated.

Overall, 50.4% of the patients with iNHL and 55.4% of those with CLL needed to stop treatment or reduce the dose. Survival without cancer worsening was 67% longer in patients with iNHL who had 2 or more treatment interruptions compared to 0.

Survival without cancer worsening was 50% longer in patients with CLL who had 2 or more treatment interruptions compared to 0. Overall survival was also 69% longer in patients with CLL who had 2 or more treatment interruptions compared to 0. These clinical benefits were maintained in patients with CLL who had a treatment interruption after receiving idelalisib for more than 6 months. Treatment interruption complemented by dose reduction did not worsen clinical outcomes.

This study showed that idelalisib interruption and dose reduction due to side effects were associated with improved clinical outcomes for patients with r/r iNHL or CLL.

This study focused on data from a small number of patients with iNHL. These results need to be verified in clinical trials that recruit a larger number of patients.