Preliminary Data Show Potential Effectiveness of Lisaftoclax Against Waldenström Macroglobulinemia

A study presented by Sikander Ailawadhi, MD, of the Mayo Clinic in Jacksonville, Florida, at the 2023 American Society of Clinical Oncology Annual Meeting sought to determine the safety and efficacy of lisaftoclax alone or in combination with ibrutinib or rituximab in patients with Waldenström macroglobulinemia (WM).

Lisaftoclax is a novel oral BCL-2 inhibitor that is under investigation as a potential treatment for hematologic malignancies.

The study had three arms:

• Arm A: lisaftoclax alone in patients who were resistant or intolerant to Bruton’s tyrosine kinase (BTK) inhibition (n=14)
• Arm B: lisaftoclax plus ibrutinib in treatment-naïve patients (n=24)
• Arm C: lisaftoclax plus rituximab in BTK inhibition-naïve patients with relapsed or refractory disease (n=8)

Patients were mostly male (75%-78.6% across arms) and had a median age of 65.0 to 67.5 years. They received escalating doses of lisaftoclax (range, 400-1,200 mg). The median duration of treatment varied by arm: six months in Arm A, 14 months in Arm B, and eight months in Arm C.

Overall response rates were 25.0% in Arm A, 90.9% in Arm B, and 37.5% in Arm C. Lisaftoclax-related grade ≥3 adverse events included neutropenia (13%), leukocytopenia (4.3%), anemia (2.2%), weight loss (2.2%), and septic shock (2.2%). No patients developed ventricular arrhythmia. Only one patient required a dose reduction; 14 patients discontinued treatment due to disease progression, and one left the study because of an adverse event.

The authors concluded, “Lisaftoclax alone or combined with ibrutinib/rituximab demonstrated measurable effects in patients with naïve or BTK inhibition-treatment-failed WM.”

Reference

Ailawadhi S, Lasica M, Fu C, et al. Preliminary data of a phase 1b/2 study of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM). Abstract #7569. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.