Exciting Activity in Chronic Lymphocytic Leukemia

In season 4, episode 7 of Targeted Talks, Cyrus M. Khan, MD, a hematologist at Allegheny Health Network, discusses the latest FDA activity in the chronic lymphocytic leukemia (CLL) space.

Beginning with the early 2023 FDA approval of zanubrutinib (Brukinsa) for the treatment of adult patients with CLL and small lymphocytic leukemia (SLL), Khan explains that the Bruton’s tyrosine kinase (BTK) inhibitor demonstrated non-inferiority compared with the standard-of-care (SoC) combination of bendamustine and rituximab (Rituxan). This approval was granted based on findings from the ALPINE (NCT03734016) and SEQUOIA (NCT03336333) studies.

“Both studies showed that the use of zanubrutinib produced superior results for these patients. In the case of the ALPINE study, the 24-month [progression-free survival] rate was 79.5% with the next generation BTK inhibitor compared with 67.3% for patients on ibrutinib [Imbruvica],” said Khan in the interview with Targeted Talks.

Recently, the FDA Oncologic Drugs Advisory Committee (ODAC) also voted against the approval of duvelisib (Copiktra) for the treatment of relapsed or refractory CLL/SLL. Khan highlights the ODAC discussion on duvelisib and other PI3K inhibitors, as well as the findings from the phase 3 DUO trial (NCT02004522), which support the new drug application.

“The problem with these drugs has been the side effect profile. We’ve had autoimmune problems come up, like pneumonitis, transaminitis, colitis, etc., and infectious complications. Then, in some of the studies, the overall survival has been poorer on PI3 kinase inhibitors rather than the standard of care,” says Khan.

During the discussion, Khan also talks about the tablet formulation of acalabrutinib (Calquence) being approved to improve absorption in patients, and agents newly granted fast track and orphan drug designations by the FDA. According to Khan, an agent to watch is the BTK inhibitor pirtobrutinib (Jaypirca), which is under investigation in the phase 1/2 BRUIN study (NCT03740529).

“Patients do progress on BTK inhibitors…I’m hoping that drug gets approved for patients that progress on the current BTK inhibitors,” Khan says.