FDA Approves Zanubrutinib for the Treatment Waldenströms Macroglobulinemia


Zanubrutinib has been approved by the FDA for the treatment of patients with Waldenströms macroglobulinemia based on the results of the phase 3 ASPEN trial.

Zanubrutinib (Brukinsa) has been approved by the FDA for the treatment of patients withWaldenströms macroglobulinemia, according to a press release from the FDA.1

The approval was based on the results of the phase 3 ASPEN trial (NCT03053440), which compared the efficacy of zanubrutinib vs ibrutinib (Imbruvica) within a population of patients with Waldenströms macroglobulinemia.2 Findings from the trial indicated that while not statistically significant, zanubrutinib yielded a higher rate of very good partial response (VGPR) of 28% vs 19% with ibrutinib (P = .09). By International Workshop for Waldenströms Macroglobulinemia (IWWM) criteria, the VGPR rate was 16% vs 7% in the 2 arms, respectively.

“We are delighted by today’s FDA approval for Brukinsa in its second indication, offering a new treatment option with demonstrated efficacy and safety benefits for patients with Waldenström’s macroglobulinemia. As shown in the ASPEN trial, Brukinsa can improve treatment outcomes for these patients and potentially make a positive impact on their lives,” Jane Huang, MD, chief medical officer of hematology at BeiGene, said in a press release.

The multicenter, open-label trial enrolled and randomized a total of 201 patients with MYD88-mutant disease to cohort 1. The trial’s primary efficacy end point was VGPR in the overall intent-to-treat population.

The major efficacy outcome of response rate was defined as patients achieving a PR or better by independent review committee. Based on IWMM-6 criteria, zanubrutinib yielded a response rate of 78% (95% CI, 68%-85%) vs 78% with ibrutinib (95% CI, 68%-86%). Moreover, the 12-month event-free duration of response was 94% (95% CI, 86%-98%) with the experimental agent compared with 88% (95% CI, 77%-94%) in the ibrutinib arm.

“The ASPEN trial provided compelling evidence that Brukinsa is a highly active BTK inhibitor in Waldenström’s macroglobulinemia, and compared to the first-generation BTK inhibitor, showed improved tolerability across a number of clinically important side effects. The approval of BRUKINSA provides an important new option for targeted therapy in Waldenström’s macroglobulinemia,” Steven Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia Research at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School, said in a statement.

Common adverse effects included decrease neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.

“The approval of Brukinsa in Waldenström’s macroglobulinemia, which is the second therapy approved specifically for the treatment of this rare type of lymphoma, is positive news for patients. Expanded treatment options offer new hope for those living with this disease and can potentially improve patient experience, especially oral therapies that can be given as a single agent,” Pete DeNardis, chair of the board at the International Waldenström’s Macroglobulinemia Foundation, said in a statement.


  1. U.S. FDA grants BRUKINSA® (Zanubrutinib) approval in Waldenström’s macroglobulinemia. News release. BeiGene, Ltd. September 1, 2021. Accessed September 1, 2021. https://bwnews.pr/3gUe6kZ
  2. Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136(18):2038–2050. doi:10.1182/blood.2020006844
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