Dr Choi on Potential Treatment Options in R/R CLL Following Progression on a Covalent BTK Inhibitor

Michael Choi, MD, hematologist/medical oncologist, associate professor of medicine, Moores Cancer Center, University of California San Diego (UCSD) Health, discusses treatment options for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) following progression or unacceptable toxicity on treatment with a prior covalent BTK inhibitor.

The number of viable options for patients following disease progression on a previous covalent BTK inhibitor and BCL-2 inhibitor has increased with the FDA approval of pirtobrutinib (Jaypirca) in pretreated CLL or small lymphocytic lymphoma (SLL), Choi begins. The noncovalent BTK inhibitor gained accelerated FDA approval on December 1, 2023, based on data from the phase 1/2 BRUIN trial (NCT03740529), in which pirtobrutinib produced an overall response rate of 72% in the cohort of patients with CLL/SLL (n = 108).

The agent also exhibits a favorable safety profile, with an adverse effect profile comparable with that of other BTK inhibitors and a potentially lower cardiovascular event rate, Choi adds. Initial data suggest that many patients can achieve and sustain remission for at least a year, indicating encouraging outcomes with this therapy, he notes.

There are several promising options are coming down the pike for patients who experience progression on pirtobrutinib, Choi continues. The novel class of BTK degraders are currently being evaluated in clinical trials and have shown early signals of activity, he states. Moreover, bispecific antibodies and CAR T-cell therapy have been explored in this space for several years, Choi adds. The ongoing development of CAR T constructs, novel targets, and innovative combinations regimens with BTK inhibitors indicates the field's commitment to addressing evolving challenges in CLL treatment, Choi emphasizes. Although the hope is that most patients can be effectively managed with covalent BTK inhibitors and venetoclax, these emerging alternatives ensure a prepared and adaptable approach to meet the diverse needs of patients with CLL, he concludes.