There is high unmet need for treatment of unfit patients with relapsed CLL, particularly in those characterized by adverse prognostic factors including del (17p) and/or TP53 mutations. Idelalisib is a first-in-class, targeted, highly selective, oral inhibitor of PI3 Kinase-delta enzyme recently approved for the treatment of relapsed CLL in combination with rituximab. During the 56th annual meeting of the American Society of Hematology (ASH) updated results were presented from a phase III study evaluating idelalisib in combination with rituximab in patients with relapsed CLL.
This study tested the efficacy of idelalisib in combination with rituximab compared to placebo with rituximab in patients with relapsed and refractory CLL who were considered unfit to receive cytotoxic therapy due to comorbidities, poor kidney function, or myelosuppression. 220 randomized patients (110 per group) received idelalisib + rituximab or a placebo + rituximab. At progression, patients were given the option of enrolling in an extension study where they would receive idelalisib. The primary endpoint was progression free survival.
At the first interim analysis, the results supported a marked improvement for patients who received idelalisib + rituximab compared with placebo + rituximab, with the median PFS not reached for patients taking idelalisib + rituximab compared with 5.5 months for patients taking the placebo. At 12 months, PFS rates for patients on idelalisib + rituximab was 66% compared to 13% for placebo + rituximab. The benefit favoring idelalisib + rituximab was seen in all risk‑groups. At the time of this analysis, 19 total deaths had occurred on the primary study: 6 on idelalisib + rituximab and 13 on placebo + rituximab.
For patients unfit to receive chemotherapy with relapsed CLL, idelalisib + rituximab demonstrated significant improvement over placebo + rituximab in terms of PFS, ORR, and OS with an acceptable safety profile. These results confirm the 1st interim analysis of the study.