A version of this article was originally published on OncLive. This version has been lightly edited.
The National Medical Products Administration (NMPA) of China has approved zanubrutinib for use in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and Waldenstrom’s macroglobulinemia (Burkinsa) approved two additional new drug applications.1
In addition, the NMPA approved two additional applications for zanubrutinib for the treatment of adult patients with CLL/SLL and mantle cell lymphoma who have received at least one prior therapy and for the treatment of adult patients with Waldenstrom’s macroglobulinemia. Switched conditional approval to normal approval. Those who have received at least one prior treatment.
“[Patients with] CLL/SLL and Waldenström macroglobulinemia are primarily [older]And there is a growing need for improved efficacy and safety in the treatment of CLL/SLL and Waldenström’s macroglobulinemia,” said Director of the Harbin Institute of Hematology and Oncology and Chief Director of the Supervisory Committee of the Chinese Society of Medical Oncology. Professor Ma Jun, a researcher, said: mentioned in the news release. “[Zanubrutinib] Both national and international guidelines recommend it as the preferred regimen for multiple subtypes of lymphoma. With these important acknowledgments, [zanubrutinib] It is currently the only new-generation BTK inhibitor approved in China for first-line treatment in adults. [patients with] CLL/SLL and Waldenström macroglobulinemia bring Chinese healthcare providers a new standard of care for their patients. “
Approval of zanubrutinib in treatment-naïve patients with CLL/SLL was supported by data from the phase 3 SEQUOIA trial (NCT03336333) and approval of a BTK inhibitor in patients with Waldenström’s macroglobulinemia was supported by the phase 3 ASPEN trial (NCT03053440) based on the results of ).
The SEQUOIA findings show that treatment-naïve CLL/SLL patients without 17p deletions enrolled in a randomized cohort had a median follow-up of 25.0 months and a median progression-free survival (PFS) not achieved (95%). CI) was achieved. , unestimable [NE]-NE) zanubrutinib group vs bendamustine and rituximab group (Rituxan; BR; HR, 0.42; 95% CI, 0.28-0.63; P < .0001).2 In this group, zanubrutinib elicited an overall response rate (ORR) of 93% (95% CI, 89%-96), including a complete response (CR) rate of 7%.
Treatment-naïve patients with 17p deletion CLL/SLL (n = 110) enrolled in a separate nonrandomized cohort of SEQUOIA and treated with zanubrutinib had an ORR of 88% (95% CI, 81%–94%). I experienced. CR rate 6%. With an estimated median follow-up of 25.1 months, the median duration of response (DOR) was NE (95% CI, NE-NE). The median time to response was 2.9 months (range, 1.9–13.9 months).
To be eligible for enrollment, patients must be ineligible for treatment with fludarabine, cyclophosphamide, and rituximab, be at least 65 years of age, or 18–64 years of age, and have a total cumulative disease rating scale of 2000. is defined as greater than or equal to 6, her creatinine clearance between 30 and 69 mL/min or history of severe or recurrent infections;
Patients without 17p del received 160 mg zanubrutinib twice daily until disease progression or unacceptable toxicity (n=241) plus 6 cycles of BR consisting of bendamustine 90 mg/m2 per day initially They were randomly assigned to treatment groups (n=238). Rituximab 375 mg/m2 on Day 1 of Cycle 1 and 500 mg/m2 on Day 1 of Cycles 2-6 in addition to 2 days of each 28-day cycle. All patients with 17p del received zanubrutinib 160 mg twice daily until disease onset. Progressive or unacceptable toxicity.
Regarding safety, serious adverse reactions (AEs) occurred in 36% of patients receiving zanubrutinib. Serious AEs observed in at least 5% of patients consisted of COVID-19, pneumonia, and second primary malignancies (5% each). Fatal AEs were reported in 4.6% of his patients, and the leading cause of death was her COVID-19 (2.1%).
In ASPEN, patients with Waldenstrom’s macroglobulinemia treated with zanubrutinib (n = 102) had an ORR of 77.5% (95% CI, 68.1%–85.1%) compared to 77.8% with ibrutinib ( 95% CI, 68.3%–85.5%) (imbruvica; n = 99). No patient achieved a CR in either group. 28.4% of patients in the zanubrutinib group had a very good partial response compared to 19.2% of patients in the ibrutinib group. The estimated 12-month DOR rate was 87.9% (95% CI, 77.0%-93.8%) with ibrutinib versus 94.4% (95% CI, 85.8%-97.9%) with zanubrutinib.
Patients in Cohort 1 (n = 201) received zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity 1: 1 randomly assigned.
The primary endpoint of the trial was response rate, defined as achieving at least a partial response by an independent review committee based on the Waldenstrom’s International Workshop on Macroglobulinemia-6 Criteria. DOR served as another important efficacy endpoint.
Safety findings from ASPEN Cohort 1 showed that 44% of patients treated with zanubrutinib experienced serious adverse events. Serious AEs reported in ≥2% of patients included influenza (3%), pneumonia (4%), neutropenia and neutropenia (3%), and hemorrhage (4%). , fever (3%), and febrile neutropenia (3%). %).
In January 2023, the FDA approved zanubrutinib for the treatment of patients with CLL/SLL, a regulatory decision supported by data from SEQUOIA and the Phase 3 ALPINE trial (NCT03734016).3 The FDA approved zanubrutinib for the treatment of adult patients with Waldenström’s macroglobulinemia in September 2021 based on ASPEN data.Four
References
1. BeiGene receives new approval for BRUKINSA® (zanubrutinib) in China. news release. Bei Gene. May 6, 2023. Accessed May 8, 2023. https://ir.beigene.com/news/beigene-receives-new-approvals-for-brukinsa-zanubrutinib-in-china/7e5cd979-7835-4263-8dde-f426c721fb3e/
2. Zanubrutinib. Prescribing Information. 2023. Accessed May 8, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213217s007lbl.pdf
3. The FDA has approved zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. news release. FDA. January 19, 2023. Accessed May 8, 2023.
4. FDA approves zanubrutinib for Waldenstrom’s macroglobulinemia. news release. FDA. August 31, 2021. Accessed May 8, 2023.