From the Journals

Venetoclax shows muscle against CLL relapsed after idelalisib



For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax 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 [Imbruvica]. 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,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.


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