Data of the combination of acalabrutinib and AZD9150 in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) from a phase 1 study were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

“Patients with R/R DLBCL after prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) therapy have poor outcomes with limited treatment options,” explained Mark Roschewski, MD, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, and colleagues. “Acalabrutinib, a highly selective, covalent, potent next-generation inhibitor of Bruton’s tyrosine kinase (BTK), is approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia and is being explored in combination with other rational targeted agents in DLBCL,” continued Dr Roschewski and colleagues.

A total of 17 patients with R/R DLBCL at a median age of 72 (range 34-88) years were enrolled in the study. Patients were administered acalabrutinib at 100 mg twice daily until disease progression or discontinuation starting on cycle 1 day 1. AZD9150 was administered at 200 mg as a 1-hour intravenous infusion on day 1, day 3, and day 5 of cycle 1, followed by weekly infusions.

Among these patients, 24 percent achieved an overall response rate (ORR), and 12 percent reached a complete response (CR).

Adverse events (AEs) reported included anemia, AST/ALT elevation, thrombocytopenia, neutropenia, and fatigue. No treatment related deaths were reported. The total cell-free DNA (cfDNA) levels and frequency of mutations correlated with treatment response. Early complete response correlated with changes in ctDNA. Persistent copy number changes were less likely to respond to acalabrutinib plus AZD9150.

“Targeting BTK and STAT3 is safe and tolerable in relapsed DLBCL but has limited efficacy. Early clearance of copy number variations and decreased cfDNA levels were associated with clinical responses and may be a useful biomarker with targeted agents,” concluded Dr Roschewski and colleagues.

Mark R, Munugalavadla V, Nuttall B, et al. Aspacytarabine (BST-236) A Phase 1 Study of the Combination of Acalabrutinib and AZD9150 in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1418.