Zanubrutinib Demonstrates Favorable Long-term Efficacy and Safety in Relapsed/Refractory MCL

Zanubrutinib demonstrated deep and durable responses and a favorable safety profile in treating relapsed/refractory mantle cell lymphoma (MCL) at a median of 35.3 months follow-up, according to a phase 2 study published in Blood.

“In November 2019, zanubrutinib received accelerated approval in the United States as a treatment for MCL in adults with ≥1 prior therapy. This was based on a phase 2 study (BGB-3111-206) with 18.4 months follow-up,” explained Yuqin Song, MD, Peking University Cancer Hospital & Institute, Beijing, China, and colleagues.

This study reports on longer-term safety and efficacy of zanubrutinib in patients with MCL with a median follow-up of 35.3 months. The primary end point of the study was overall response rate (ORR).

A total of 86 patients were enrolled in the study from 13 sites in China. Zanubrutinib was administered orally at a dose of 160 mg twice daily until progressive disease (PD), unacceptable toxicity, death, or withdrawal of consent.

At a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response; the median duration of response was not reached. Median progression-free survival (PFS) was 33 months (95% confidence interval [CI], 19.4 to not estimable). The 36-month PFS and overall survival rates were 47.6% (95% CI, 36.2 to 58.1) and 74.8% (95% CI, 63.7 to 83), respectively.

The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported.

In conclusion, Dr Song and colleagues noted, “this phase 2 study in patients with R/R MCL with extended 35.3-month follow-up data continued to demonstrate a favorable benefit–risk profile of zanubrutinib monotherapy in [relapsed/refractory] MCL patients. Approximately 50% of patients remain progression-free at 36 months.”

Source: 

Song Y, Zhou K, Zou D, et al. Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. 2022;139 (21):3148–3158. doi:10.1182/blood.2021014162