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Jennifer R. Brown, MD, PhD


MRD-Driven, Time-Limited Triplet Therapy Under Study in CLL

By: Julia Fiederlein Cipriano
Posted: Wednesday, November 23, 2022

Adding the PI3Kδ and CK1ε inhibitor umbralisib and the anti-CD20 monoclonal antibody ublituximab to ibrutinib therapy seems to be safe and active in patients with chronic lymphocytic leukemia (CLL) who had detectable measurable residual disease (MRD), according to Lindsey E. Roeker, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. The results of this phase II study, which were published in the journal Clinical Cancer Research, also demonstrated the durability of a period of treatment-free observation after this MRD-driven, time-limited therapy.

“While effective as approved, ibrutinib is administered as a continuous therapy with a treat-to-progression strategy, and the use of ibrutinib is limited by intolerance and resistance,” the investigators remarked. “For ibrutinib-treated patients with CLL with response but persistent MRD, an ‘add on’ approach was designed to increase [the] depth of response with the goal to convert a treat-to-progression continuous therapy to a time-limited one.”

A total of 28 patients who received ibrutinib in any line of therapy for at least 6 months and had detectable MRD were administered umbralisib plus ublituximab. They entered a period of treatment-free observation after undetectable MRD was achieved or 24 cycles of this triplet therapy were administered.

Of the 27 efficacy-evaluable patients, 52% achieved confirmed undetectable MRD per protocol, and 78% had at least one undetectable MRD evaluation. After a median of 6.4 months of treatment with triplet therapy, 63% of patients entered a period of treatment-free observation. The estimated 12-month progression-free survival rate was 95%. Hypertension (7%), diarrhea (4%), and increased levels of alanine transaminase/aspartate transaminase (4%) of grade 3 or higher were reported in the safety cohort.

Disclosure: For full disclosures of the study authors, visit

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