Ongoing Studies in CLL Look Towards New Treatment Options

Alexey Danilov, MD, PhD, associate director, Toni Stephenson Lymphoma Center, and professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, discusses some targeted therapies being investigated in the relapsed/refractory chronic lymphocytic leukemia (CLL) space.

There are a number of targeted agents currently available for patients with CLL, including Bruton tyrosine kinase (BTK) inhibitors, PI3K inhibitors, B-cell lymphoma 2 inhibitors, venetoclax (Venclexta), and more.

On top of these agents, there is a lot of early and encouraging data from newer studies. These trials are evaluating combination therapies, chimeric antigen receptor (CAR) T-cell therapies and pirtobrutinib (L0X0-305), a noncovalent BTK inhibitor.

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0:08 | There are many studies going on now, which use the combination therapy of both BTK inhibitors and BCL-2 inhibitors, such as acalabrutinib [Calquence] and venetoclax or ibrutinib [Imbruvica] and venetoclax. The data from the studies are already emerging, and the early data is very encouraging. Those are time limited therapies in CLL.

0:32 | In addition, there are multiple other targeted agents being developed. For example, double refractory patients who have relapsed on both BTK inhibitors and the BCL-2 inhibitor venetoclax represent an unmet medical need now. Novel agents such as noncovalent BTK inhibitors like pirtobrutinib are being developed in that space. There are some novel BCL-2 inhibitors as well which are in clinical trials. BTK degraders, which have a slightly different mechanism where they don't just block the BTK, but lead to its degradation, are also In early phase clinical trials now with very limited data so far.

1:22 | In terms of immune or cell therapy approaches, there are some exciting data emerging with the CAR T-cell therapies which show efficacy in double refractory CLL as well, and here are several trials with bispecific antibodies, such as mosunetuzumab [Lunsumio], which also show early promise.