CLL Highlights From ASH 2019

William G. Wierda, MD, PhD


January 06, 2020

Key studies on next-generation BTK inhibitors and combination treatments for chronic lymphocytic leukemia (CLL) were presented at the 2019 American Society of Hematology (ASH) meeting.

Dr William Wierda of MD Anderson Cancer Center reviews data from the ELEVATE-TN trial, a three-arm randomized trial of acalabrutinib, a second-generation BTK inhibitor. The study compares single-agent acalabrutinib versus acalabrutinib plus obinutuzumab, versus chlorambucil plus obinutuzumab. On the basis of the ELEVATE-TN and ASCEND trials, acalabrutinib has recently been approved for both previously treated and treatment-naive patients with CLL.

Two studies of zanubrutinib, another BTK inhibitor, are also reviewed. The SEQUOIA study, of treatment-naive CLL patients with high-risk del(17p) disease, showed a high rate of durable partial response. Similarly, 90% of patients responded to treatment in a phase 1/2 study of zanubrutinib for both treatment-naive and relapsed/refractory CLL.

Updates on combination-therapy studies of ibrutinib plus venetoclax are discussed, in which deep remissions were achieved with or without CD20 antibody. Also seen were high rates of minimal residual disease in bone marrow after 1 year of treatment.

Finally, Dr Wierda reviews a first-in-human phase 1 trial of the non-covalent BTK inhibitor LOXO-35. This agent shows promise for patients who have developed resistance to irreversible BTK inhibitors. A majority of patients responded to this treatment and suffered no dose-limiting toxicities.


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