Early Results With Chemotherapy-Free Triplet Regimen in Resistant CLL
Posted: Wednesday, January 15, 2020
For patients with relapsed or refractory chronic lymphocytic leukemia (CLL), a chemotherapy-free triplet regimen appears to be capable of inducing undetectable minimal residual disease (MRD) after just 12 treatment cycles, according to phase I/II study results reported at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 360). In phase I, the primary endpoint was safety of the umbralisib, ublituximab, and venetoclax combination, reported Paul M. Barr, MD, of Wilmot Cancer Institute at the University of Rochester in New York, and colleagues. In phase II, the primary and key secondary endpoints were complete remission rate and MRD negativity, respectively.
Umbralisib is a novel, highly specific PI3Kδ inhibitor; ublituximab is a chimeric monoclonal antibody that targets a unique epitope on CD20; and venetoclax is a BCL2 inhibitor.
A total of 21 patients participated: 9 in phase I and 12 in phase 2. “In evaluable patients, the overall response rate was 85% after cycle 3, 100% after cycle 7, and 100% after cycle 12,” described Dr. Barr and his team. With two complete and three partial responses reported in the five patients who finished 12 therapy cycles, the median reduction in nodal disease was 87%. After a median 4.2-month follow-up, no patients had experienced disease progression.
The 21 patients had had a median of two previous treatments, and their median age was 65 years. Of nine patients who had had prior treatment with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, four were found to be refractory to BTK inhibitors, and BTK resistance mutations were discovered in two. Although the baseline risk of tumor-lysis syndrome was high, medium, and low in 2, 12, and 7 patients, respectively, no tumor-lysis syndrome events were observed.
A planned multicenter trial, focusing on patients who relapsed after using BTK inhibitors, will further develop the triplet regimen.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
