The U.S. Food and Drug Administration (FDA) has approved zanubrutinib for the treatment of adult patients with Waldenström macroglobulinemia (WM).
This approval is based on efficacy data from the ASPEN trial comparing zanubrutinib with ibrutinib in adult patients with MYD88 L265P─mutated WM. In Cohort 1, 201 patients were randomized to receive either zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. Patients in Cohort 2 had MYD88 wildtype (n=26) or MYD88 mutation unknown WM (n=2) and were treated with zanubrutinib 160 mg twice daily.
Outcomes used to support approval were partial response or better as assessed by an independent review committee based on standard consensus response criteria from the International Workshop on Waldenström’s Macroglobulinemia-6, as well as duration of response (DOR). Across all patients receiving zanubrutinib, the response rate was 77.5%. At 12 months, the event-free DOR for patients treated with zanubrutinib was 94.4%. In Cohort 2, response as assessed by independent review committee was seen in 50% of response evaluable patients (13 out of 26).
Adverse events reported in ≥20% of patients treated with zanubrutinib were neutropenia, upper respiratory tract infection, thrombocytopenia, rash, hemorrhage, musculoskeletal pain, anemia, bruising, diarrhea, pneumonia, and cough.
The recommended oral dosage of zanubrutinib is 160 mg twice daily or 320 mg once daily.