Venetoclax Active in CLL Progressing After Idelalisib

Venetoclax had promising clinical activity, with a high objective response rate among patients with relapsed or refractory chronic lymphocytic leukemia (CLL) previously treated with idelalisib, according to the results of a study published in Blood.

“Venetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib,” wrote Steven Coutre, MD, MPH, of Stanford Cancer Center, and colleagues. “These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients.”

According to the study, the efficacy of therapies for patients whose disease is refractory to or relapsed after treatment with B-cell receptor pathway inhibitors is currently unknown. Venetoclax is a BCL-2 inhibitor that has been shown to be active in patients with CLL, including those with heavily pretreated disease or those with a 17p deletion.

In this study, the researchers evaluated venetoclax in patients with relapsed or refractory CLL previously treated with ibrutinib or idelalisib. These results are for those 36 patients last treated with idelalisib.

All patients had venetoclax initiated at 20 mg daily followed by intra-patient ramp-up to 400 mg daily. The primary objectives were objective response rate and safety.

The objective response rate was 67%, with 24 of 36 patients responding. Two patients achieved complete remission, and one had complete remission with incomplete bone marrow recovery. Twenty-one (58%) patients had a partial response. The median time to first response was 2.5 months.

The median progression-free survival has not yet been reached, and the estimated 12-month progression-free survival rate was 79%.

Most grade 3/4 adverse events were primarily hematologic, including neutropenia (50%), thrombocytopenia (25%), and anemia (17%). No patients had febrile neutropenia, and there were no deaths attributed to adverse events.

“The safety profile for venetoclax post-idelalisib is consistent with previous reports of venetoclax monotherapy in relapsed/refractory CLL, as well as in patients who received venetoclax post-ibrutinib,” the researchers wrote. “All patients followed the 5-step dose ramp-up (one patient received venetoclax over a compressed 3-week schedule) and by implementing risk-based prophylactic measures and close monitoring, tumor lysis syndrome was not observed, despite many of these patients having rapidly progressive CLL after discontinuing idelalisib.”

Based on this, clinicians starting patients on venetoclax after progressing on idelalisib should closely follow label guidelines to mitigate the risk for tumor lysis syndrome, the researchers recommended.