ASH 2017 | BGB-3111 BTK inhibitor use in patients with indolent and aggressive NHL

The 59^th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on 9–12 December 2017. On Saturday December 9^th, an oral abstract session was held on “Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Indolent Lymphomas, Novel Therapies, and Diagnostics”. This session was moderated by Jonathon B. Cohen, Emory University - Winship Cancer Institute and Craig A. Portell, University of Virginia.

Abstract #152 was presented during this session, titled “Safety and Activity of the Highly Specific BTK Inhibitor BGB-3111 in Patients with Indolent and Aggressive Non-Hodgkin’s Lymphoma” by Constatine S. Tam, Peter MacCallum Cancer Centre & St. Vincent's Hospital, Melbourne, Australia and colleagues.

Study highlights

• Overall, 99 patients with relapsed or refractory B-cell malignancies were included in the Phase Ib study split into two groups:
  • Aggressive lymphoma (AL): 27 diffuse large B-cell lymphoma (DLBCL), 38 mantle cell lymphoma (MCL)
  • Indolent lymphoma (IL): 24 follicular lymphoma (FL), 10 marginal zone lymphoma (MZL)
• Patients were treated with Bruton’s Tyrosine Kinase (BTK) inhibitor zanubrutinib (BGB-3111), 160 mg twice daily

Efficacy

• In total, 84 patients were assessed for treatment efficacy including objective response rate (ORR), complete response (CR) and partial response (PR)
  • ORR in indolent lymphoma patients (n = 26): 14 (54%)
    • ORR in FL patients (n = 17): 7 (41%)
    • ORR in MZL patients (n = 9): 7 (78%)
  • ORR in aggressive lymphoma patients (n = 58): 36 (62%)
    • ORR in DLBCL patients: 8 (31%)
    • ORR in MCL patients: 28 (88%)

Safety

• Grade ≥3 adverse events (AEs) 38% from the IL arm, 60% from the AL arm had more than one
• Serious AE: 32% of the IL patients and 40% of the AL patients had more than one serious AE
• One fatal AE occurred in the IL cohort and six patients died due to AEs in the AL group

The authors concluded that BGB-3111 had an acceptable safety profile and was shown to have good clinical activity in both indolent and aggressive NHL subtypes, which is being further evaluated in phase II trials. AEs led to discontinuation in 10% of patients overall.

Watch the full interview with Constantine Tam discussing the BGB-3111 trial here.