Anthony R. Mato, MD
The next generation PI3K-delta inhibitor umbralisib (TGR-1202) showed promising safety results while inducing durable responses in high-risk patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to data from a phase II study.
during the 2018 European Hematology Association Congress, Mato discussed the next steps for umbralisib and the biggest challenges still facing patients with CLL.
OncLive: What was the rationale for this study?
: In clinical practice, about half of the discontinuation of drugs like ibrutinib (Imbruvica) or idelalisib (Zydelig) have been due to a toxicity or AE. What we've noticed, at least retrospectively, is that those side effects tend to be different—the ibrutinib-related toxicities are different than the idelalisib-related toxicities. From a retrospective study that we did, we noticed that in practice, when patients are switched from ibrutinib to idelalisib or idelalisib to ibrutinib in the setting of intolerance, you could maintain the response without having to switch to another agent. We felt that this intolerant patient population was a large number of patients and that this was an unmet clinical need.
This is a multicenter trial. Fourteen centers participated across the United States. The study, as of September of [last] year fully accrued and we have 50 patients who participated in this study. [I presented] safety data on 47 of the 50 patients, and data on the primary endpoint, which is PFS, on 46 of the patients.
What were the safety results?
In the 47 patients, there were 68 total toxicity events that led to discontinuation, and they're the ones that you would expect. From the BTK inhibitors, we had bleeding events; for example, this includes atrial fibrillation. From the PI3K inhibitor part of the cohort, we had patients who had colitis and pneumonitis.
The patient population is a relatively typical relapsed/refractory CLL population, although there are significant high-risk features. The median age was 72, median number of prior therapies was 2, 85% of patients discontinued a prior BTK inhibitor, and 15% [discontinued] a PI3K inhibitor.
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