Chronic Lymphocytic Leukemia Coverage from Every Angle

Umbralisib in Kinase Inhibitor–Intolerant CLL

By: Melissa E. Fryman, MS
Posted: Thursday, August 8, 2019

Patients with chronic lymphocytic lymphoma (CLL) who do not respond to treatment with kinase inhibitors may benefit from umbralisib, according to Anthony R. Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. The researchers reported that the highly specific PI3K delta inhibitor is tolerated well in patients with CLL. They presented their findings at the 2019 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (Abstract 050).

“These are the first prospective data to confirm that switching from [a kinase inhibitor] to [umbralisib] can result in durable, well-tolerated responses,” concluded the researchers. “From a therapy-sequencing perspective, these data suggest use of an alternate [kinase inhibitor] is a reasonable strategy prior to class switch to a BCL2 inhibitor.”

In this study, a total of 50 kinase inhibitor–intolerant patients were treated with umbralisib and evaluable for analysis. The median age for this cohort was 70 years, and patients had a median of two prior therapies. A majority of patients (76%) commenced umbralisib within 6 months of prior kinase inhibitor discontinuation. At the cutoff date, 58% of patients had been on umbralisib for a longer period than they had been with prior kinase inhibitor therapies. The median progression-free survival was 23.5 months.

Umbralisib treatment was discontinued for six patients due to adverse events. The most common grade 3 or higher adverse events were neutropenia, thrombocytopenia, diarrhea, hypophosphatemia, and pneumonia. Of the four patients who experienced the same adverse events that led to prior kinase inhibitor intolerance, three did not require dose modification. None of the patients who discontinued prior PI3K inhibitor treatment due to adverse events experienced the same adverse events.

Disclosure: The study authors’ disclosure information can be found at

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