Zanubrutinib Approved in Uruguay for MCL, MZL, and Waldenström Macroglobulinemia

The BTK inhibitor zanubrutinib (Brukinsa) has been approved in Uruguay for the treatment of adult patients with previously treated mantle cell lymphoma (MCL), relapsed or refractory marginal zone lymphoma (MZL), and Waldenström macroglobulinemia (WM).1

“Tolerability of treatments for B-cell malignancies is an important consideration with BTK inhibition, and [zanubrutinib] was designed with that in mind to maximize BTK occupancy and minimize off-target binding. [Now] we have a new treatment option for patients with MCL, MZL and WM in Uruguay, providing hope for improved treatment outcomes,” Dr Karina Cicinelli, corporate medical director at Adium in Montevideo, Uruguay, stated in a press release.

Previously, the FDA approved zanubrutinib in all 3 disease indications. In November 2019, the agent was approved for the treatment of adult patients with MCL who had received at least 1 prior therapy.² In September 2021, zanubrutinib was approved for the treatment of adult patients with Waldenström macroglobulinemia.³ Later in September 2021, the FDA approved zanubrutinib for the treatment of adult patients with relapsed or refractory MZL who have received at least 1 prior anti–CD20-based regimen.⁴

Zanubrutinib has received more than 20 approvals in more than 40 countries and regions, including the United States, China, the European Union, Great Britain, Canada, Australia, and other international locations.

“We are proud of the progress BeiGene has made in Latin America over the past year, with this approval in three indications in Uruguay following recent launches in Brazil, Chile and Ecuador. With Adium’s established commercial presence in Latin America, we hope patients with MCL, MZL, and WM will soon have access to this important treatment option,” Eduardo Molinari, senior director of New Market Development in Latin America at BeiGene, stated in a press release.

In the phase 2 Chinese BGB-3111-206 trial (NCT03206970) in MCL, zanubrutinib elicited an overall response rate (ORR) of 84% (95% CI, 74%-91%), including a 59% complete response (CR) rate and a 25% partial response (PR) rate, at a median follow-up of 36 weeks (range, 1-56).⁵ The median duration of response (DOR) was 19.5 months (95% CI, 16.6-not estimable).²

The Chinese BGB-3111-206 trial evaluated zanubrutinib 86 adult patients with MCL who had received between 1 and 4 prior treatment regimens. Patients were treated with zanubrutinib at a dose of 160 mg twice daily until disease progression or unacceptable toxicity, and the trial’s primary end point was ORR assessed by an independent review committee (IRC).

In the phase 3 ASPEN trial (NCT03053440) in Waldenström macroglobulinemia, at the August 2019 cutoff, zanubrutinib elicited a CR or very good partial response rate of 28.4% compared with 19.2% in patients who received ibrutinib (Imbruvica; P = .0921).⁶ At the January 2020 data cutoff, the best ORRs for zanubrutinib and ibrutinib were 30.4% vs 18.2%, respectively (P = .0302).

Cohort 1 of ASPEN enrolled 201 patients with Waldenström macroglobulinemia and an MYD88 mutation. These patients were randomized 1:1 to receive either 160 mg of zanubrutinib twice daily (n = 102) or 420 mg of ibrutinib once daily (n = 99). Another cohort of 28 patients who did not harbor MYD88 mutations were given 160 mg of zanubrutinib twice daily. The primary objective of the trial was to evaluate the efficacy of zanubrutinib vs ibrutinib.

Regarding MZL, results from the phase 2 MAGNOLIA trial (NCT03846427) showed zanubrutinib elicited an ORR of 56% (95% CI, 43%-68%) with a complete response (CR) rate of 20% in 66 patients with relapsed/refractory MZL.⁴

The single-arm trial enrolled patients with MZL who must have received at least 1 anti–CD20-based regimen. Zanubrutinib was administered at a dose of 160 mg twice daily until patients experienced progressive disease or intolerable toxicity, and the trial’s primary end point was ORR per IRC and Lugano classification.⁷

Regarding the safety of zanubrutinib, the most common adverse effects (AEs) of any grade in patients who received the treatment as a single agent (n = 847) were decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%), and musculoskeletal pain (30%).

Fatal and serious hemorrhagic AEs have occurred with the use of single-agent zanubrutinib. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with zanubrutinib monotherapy. Hemorrhage AEs of any grade occurred in 35% of patients.

Fatal and serious infections, including bacterial, viral, or fungal, and opportunistic infections have occurred in patients with hematologic malignancies treated with zanubrutinib monotherapy. Notably, 27% of patients experienced a grade 3 or higher infection, most commonly pneumonia. Infections due to hepatitis B virus reactivation have occurred.

Grade 3 and 4 cytopenias have been reported with the use of zanubrutinib monotherapy, including neutropenia (26%), thrombocytopenia (11%), and anemia (8%). Grade 4 neutropenia occurred in 13% of patients, and grade 4 thrombocytopenia occurred in 3.6% of patients.

References

1. BeiGene announces BRUKINSA (zanubrutinib) approval in Uruguay in mantle cell lymphoma, marginal zone lymphoma, and waldenström’s macroglobulinemia. News release. BeiGene. April 28, 2022. Accessed May 25, 2022. https://bwnews.pr/3wSx4Q9
2. FDA grants accelerated approval to zanubrutinib for mantle cell lymphoma. News release. FDA. November 14, 2019. Accessed May 25, 2022. https://bit.ly/39UwVDZ
3. U.S. FDA grants BRUKINSA (zanubrutinib) approval in waldenström’s macroglobulinemia. News release. BeiGene. September 1, 2021. Accessed May 25, 2022. https://bwnews.pr/38vGDZx
4. US FDA grants BRUKINSA (zanubrutinib) accelerated approval in relapsed or refractory marginal zone lymphoma. News release. BeiGene. September 15, 2021. Accessed May 25, 2022. https://bit.ly/3zbzB6X
5. Song Y, Zhou K, Zou D, et al. Safety and activity of the investigational Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) in patients with mantle cell lymphoma from a phase 2 trial. Blood. 2018;132(suppl 1):148. doi:10.1182/blood-2018-99-117956
6. Tam CSL, Opat S, D’Sa S, et al. ASPEN: results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenström macroglobulinemia (WM). J Clin Oncol. 2020;38(suppl 15):8007. doi:10.1200/JCO.2020.38.15_suppl.8007
7. BeiGene announces data on BRUKINSA (zanubrutinib) from phase 2 trial in marginal zone lymphoma and phase 3 trial in chronic lymphocytic leukemia or small lymphocytic lymphoma at the 62nd ASH Annual Meeting. News release. BeiGene. December 6, 2020. Accessed May 25, 2022. https://bwnews.pr/3hCRyp1