Dr Danilov on Unmet Needs for Various CLL Subgroups

Alexey Danilov, MD, PhD, hematologist-oncologist, associate director, Toni Stephenson Lymphoma Center, professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the ongoing challenges and unmet needs for patients with chronic lymphocytic leukemia (CLL), including those who are younger and those with double refractory disease.

Danilov explains that double refractory CLL refers to patients who have experienced disease progression following both BTK inhibitor– and BCL2 inhibitor–based regimens. Developing additional therapies for patients in this population represents a critical unmet need in CLL, Danilov explains, noting that pirtobrutinib (Jaypirca) is one of the limited treatment options in this setting.

Although pirtobrutinib has displayed efficacy and is approved by the FDA for patients with relapsd/refractory CLL or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor, Danilov explains novel agents could help improve the median progression-free survival (PFS) displayed with pirtobrutinib. He adds that pirtobrutinib has been associated with a shorter PFS in patients who previously progressed on a covalent BTK inhibitor and a BCL2 inhibitor.

Danilov also highlights the challenges faced by younger patients with CLL who are diagnosed and begin treatment at an early age. These patients are often committed to long-term therapy, primarily involving continuous treatment with BTK inhibitors, he says. Time-limited treatment strategies for these patients is another significant unmet need, Danilov notes, explaining that these approaches could potentially reduce the long-term treatment burden.

Due to the nature of their disease, patients with CLL tend to be immune compromised, which also represents another area of concern, particularly in the context of infection development, Danilov explains. Additionally, patients with CLL have a diminished response to vaccines and are at an increased risk of infections, which remains a leading cause of morbidity and mortality in this population, he concludes.