On September 14, 2021, the FDA accelerated the approval of zanubrutinib (Brukinsa; BeiGene) for adults with relapsed or refractory marginal-zone lymphoma (MZL) who have received ≥1 anti-CD20–based regimens. Two weeks earlier, on August 31, 2021, the FDA accelerated the approval of zanubrutinib for adults with Waldenström’s macroglobulinemia (WM). Zanubrutinib received an orphan designation for these indications.
Zanubrutinib was previously approved for mantle-cell lymphoma.
The approval of zanubrutinib for MZL was based on 2 open-label, multicenter, single-arm clinical trials that together included 86 patients with previously treated MZL. Zanubrutinib was administered orally at 160 mg twice daily or 320 mg once daily.
The efficacy measures were overall response rate (ORR) and duration of response (DOR). The ORR was 56% (95% confidence interval [CI], 43%-68%) in the first study, including 20% complete responses, and 80% (95% CI, 56%-94%) in the second study, including 20% complete responses. The median DOR was not estimable.
Continued approval for this indication may be contingent on confirmatory data from a clinical trial.
The approval of zanubrutinib for WM was based on a noncomparative assessment of response and DOR from the zanubrutinib arms in 2 cohorts of the ASPEN study of patients with WM. Cohort 1 included 201 patients with WM and MYD88 L265P mutation, and cohort 2 included 26 patients with WM and wild-type MYD88 L265P. The major efficacy outcome was ORR. The secondary efficacy measure was DOR.
The ORR to zanubrutinib in cohort 1 was 77.5%, with a 12-month event-free DOR of 94.4%. In cohort 2, among the 26 enrolled patients, the ORR to zanubrutinib was 50%, which included complete and partial responses.
The most common (≥20%) adverse events reported with zanubrutinib are decreased neutrophils, upper-respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.