Zanubrutinib-Based Therapy for CLL: Focus on MRD-Driven Treatment Duration

By: Sarah Campen, PharmD
Posted: Friday, February 11, 2022

The combination of the Bruton’s tyrosine kinase inhibitor zanubrutinib with the monoclonal antibody obinutuzumab and the BCL2 inhibitor venetoclax appears to induce high rates of measurable residual disease (MRD) in treatment-naive patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), according to data published in The Lancet Haematology. This multicenter phase II trial was also reportedly the first prospective study to use MRD kinetics as the principal determinant of treatment duration and discontinuation in CLL or SLL.

“These results support MRD-directed, time-limited therapy with zanubrutinib, obinutuzumab, and venetoclax as a well-tolerated regimen for previously untreated patients with CLL or SLL,” stated Andrew D. Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.

In this trial, 39 patients with treatment-naive CLL or SLL received zanubrutinib, obinutuzumab, and venetoclax in 28-day cycles. Treatment was discontinued after 8 to 24 cycles when prespecified undetectable MRD criteria were met in the peripheral blood and bone marrow.

After a median follow-up of 25.8 months, 33 of 37 patients (89%) had undetectable MRD in both blood and bone marrow, meeting the criteria to stop therapy after a median of 10 cycles. Of the 33 patients who met the prespecified undetectable MRD endpoint and discontinued therapy, 31 (94%) had ongoing undetectable MRD in the peripheral blood, as established by flow cytometry following a median time of 15.8 months during surveillance after treatment.

As for safety, the most common adverse events were thrombocytopenia (59%), fatigue (54%), neutropenia (51%), and bruising (51%); neutropenia (18%) was the most common grade 3 or worse adverse event. One patient died of intracranial hemorrhage on day 1 of cycle 1 after initiating intravenous heparin for pulmonary emboli.

Disclosure: For full disclosures of the study authors, visit www.thelancet.com.

The Lancet Haematology