NCCN Guidelines Add Zanubrutinib as Preferred Therapy for Waldenström Macroglobulinemia

The updated guidelines from the National Comprehensive Cancer Network (NCCN) for Waldenström macroglobulinemia has added zanubrutinib (Brukinsa) as a preferred regimen.

The NCCN Guidelines Version 1.2022 Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma (WM/LPL) were updated to include zanubrutinib as a preferred regimen for the primary therapy of WM/LPL along with bendamustine/rituximab, bortezomib/dexamethasone/rituximab, ibrutinib ± rituximab, and rituximab/cyclophosphamide/dexamethasone. Preferred interventions are based on superior efficacy, safety, and evidence.

Both zanubrutinib and ibrutinib ± rituximab are considered category 1 recommendations, which means they are based on high-level evidence and there is uniform NCCN consensus that the intervention is appropriate. The other therapies are all category 2A: based on lower-level evidence, but there is still uniform NCCN consensus that the intervention is appropriate.

Zanubrutinib was also added as a category 1 preferred regimen for previously treated WM/LPL. The other preferred regimens for previously treated WM/LPL are the same as the preferred regimens for primary treatment.

The addition of zanubrutinib to the guidelines was based on the findings from the ASPEN study published in Blood. The study compared the safety and efficacy of zanubrutinib, a novel highly selective Bruton tyrosine kinase (BTK) inhibitor, with ibrutinib, a first-generation BTK inhibitor.

In ASPEN, 28% of patients on zanubrutinib and 19% on ibrutinib achieved a very good partial response (VGPR); no patient achieved a complete response (CR). The study did not meet the primary end point, which was proportion of patients achieving CR or VGPR, but the researchers noted that “there was a trend toward better disease control for zanubrutinib vs ibrutinib.”

Major response rate was similar (77% for zanubrutinib vs 78% for ibrutinib), as was progression-free survival (85% for zanubrutinib vs 84% for ibrutinib).

Patients on zanubrutinib had fewer instances of atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events that led to treatment discontinuation.

“This study established that zanubrutinib is highly effective in the treatment of WM; zanubrutinib is associated with important safety advantages, especially with respect to cardiovascular toxicity,” the authors wrote.

The data from ASPEN was used in a supplemental new drug application (sNDA) with the FDA for zanubrutinib in the treatment of WM, which was submitted in February 2021. Health Canada approved zanubrutinib in WM in March based on the findings of ASPEN.

“We are pleased that the FDA has accepted the sNDA for Brukinsa in WM, a rare disease with significant morbidity,” Jane Huang, MD, chief medical officer, Hematology, BeiGene, said in a statement. “BTK inhibitors have transformed the treatment of WM in recent years, but discrepancies in response exist in patients with different subtypes, and toxicity can remain an issue.”

Reference

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;136:2038-2050. doi:10.1182/blood.2020006844