Zanubrutinib plus venetoclax and obinutuzumab is well tolerated and achieves rapid undetectable minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL), according to a presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting (May 29-31, 2020).
Prior research has shown that time-limited venetoclax plus obinutuzumab can effectively induce undetectable MRD. Additionally, zanubrutinib has demonstrated 100% occupancy in lymphoid tissues and may be optimally used when combined with a CD20 antibody.
Jacob D Soumerai, MD, Massachusetts General Hospital, and colleagues designed a study to determine if zanubrutinib plus venetoclax and obinutuzumab can achieve frequent undetectable MRD in patients with CLL. Researchers hypothesized that their MRD-driven discontinuation strategy would lead to durable responses. The multicenter, investigator-initiated phase II trial considered 39 patients with previously untreated CLL with an ECOG performance status of less than 2, an absolute neutrophil count of at least 1000, and a platelet count of at least 75,000.
Therapy was administered in 28-day cycles and therapy duration was determined by a prespecified undetectable MRD endpoint with a minimum of eight cycles and a maximum of 24 cycles. MRD was assessed in peripheral blood (flow cytometry, sensitivity 10-4), and once determined and confirmed in bone marrow, therapy was continued for an additional two cycles.
Dr Soumerai and colleagues noted that all patients were evaluable for toxicity and 37 were evaluable for efficacy. At a median follow-up of 11 months, 62% (n = 23) of patients had achieved the prespecified peripheral blood undetectable MRD and stopped therapy after a median of 8 months.
The most common treatment-related adverse events were neutropenia (49%), infusion-related reaction (41%), bruising (39%), and diarrhea (39%). Grade 3/4 adverse events included neutropenia (13%), thrombocytopenia (5%), rash (5%), and pneumonia (5%).
In their concluding remarks, authors of the study wrote that zanubrutinib plus venetoclax and obinutuzumab is well tolerated and achieves rapid undetectable MRD in patients with CLL. “The value of MRD-directed treatment duration will be evaluated with continued post-discontinuation follow-up,” they added.—Zachary Bessette
