CLL Coverage from Every Angle

ASH 2021: Combination Umbralisib and Ublituximab With Ibrutinib in CLL

By: Vanessa A. Carter, BS
Posted: Monday, December 13, 2021

A phase II study conducted by Lindsey E. Roeker, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues analyzed the addition of the PI3Kd  and CK1e inhibitor umbralisib and the anti-CD20 monoclonal antibody ublituximab to ibrutinib in patients with chronic lymphocytic leukemia. These results, presented during the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 395), concluded that this novel combination therapy was effective and well tolerated, reaching undetectable measurable residual disease (MRD) in 71% of participants.

“This is the first measurable residual disease–driven approach utilizing the combination of a BTK inhibitor, PI3K inhibitor, and anti-CD20 monoclonal antibody,” the investigators mentioned. “This ‘add-on’ approach for patients on continuous ibrutinib resulted in deep remissions that allowed for a tailored, time-limited therapy and sustained treatment-free observation.”

This multicenter, open-label trial enrolled 26 patients with detectable residual CLL who were receiving ongoing ibrutinib for at least 6 months. Participants were administered umbralisib and ublituximab concurrently with ibrutinib and then were monitored for MRD. A period of treatment-free observation was initiated once undetectable residual disease was reached; otherwise, patients continued treatment for up to 24 cycles.

The median patient age was 63, and the majority (77%) of patients were male. The median duration of treatment with ibrutinib before the addition of umbralisib and ublituximab was 22 months. Of 24 evaluable patients, 17 were observed to have undetectable residual disease; the median time to the first result was 5 months. Additionally, 16 individuals entered treatment-free observation, with 15 presenting two consecutive assessments of undetectable residual disease.

Approximately 73% of participants sustained undetectable residual disease, and the median time off therapy was 242 days as of the data cutoff. Grade 3 or 4 adverse events such as hypertension, diarrhea, and an alanine aminotransferase/aspartate aminotransferase increase were observed in 8%, 4%, and 4% of patients, respectively.

Disclosure: For full disclosures of the study authors, visit

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