Rapid health technology assessment of zanubrutinib in the treatment of B cell lymphomas / 中国药房

OBJECTIVE To rapidly assess the efficacy， safety and cost-effectiveness of novel highly selective Bruton’s tyrosine kinase （BTK） inhibitor zanubrutinib in the treatment of chronic lymphocytic leukemia （CLL）， small lymphocytic lymphoma （SLL） and mantle cell lymphoma （MCL）. METHODS Retrieved from PubMed， Cochrane Library， CNKI， Wanfang database， VIP， and health technology assessment （HTA） websites， systematic reviews/meta-analyses， randomized controlled trials （RCTs）， pharmacoeconomic studies and HTA reports related to zanubrutinib were collected from the database/website establishment to July 2023. The literature was screened according to inclusion and exclusion criteria， and its quality was assessed by using relevant evaluation tools. Data extraction was presented by qualitative description. RESULTS A total of 5 literature were included， comprising of 3 RCTs and 2 cost-effectiveness analyses. In terms of efficacy， compared with the control group， zanubrutinib treatment resulted in significantly longer progression-free survival （P＜0.05） and a higher overall response rate （P＜0.05）. However， there was no statistical significance in overall survival between 2 groups （P＞0.05）. In terms of safety， zanubrutinib had lower incidence of cardiac adverse events， incidence of major bleeding events， and drug discontinuation rate due to adverse drug events， compared to first-generation BTK inhibitors ibrutinib； but the risk of bleeding events caused by zanubrutinib was still higher， compared to traditional chemoimmunotherapy （bendamotine+rituximab）. In terms of cost-effectiveness， zanubrutinib was found to be cost-effective in the treatment of recurrent or refractory MCL， compared to ibrutinib. CONCLUSIONS Zanubrutinib demonstrates sound efficacy and safety in patients with CLL/SLL and MCL patients. Furthermore， it exhibits economic advantages for patients with relapsed or refractory MCL.

Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

Zanubrutinib combined regimens for treatment of elderly patients with central nervous system lymphoma: report of 3 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of zanubrutinib combined regimens for treatment of elderly patients with central nervous system lymphoma (CNSL).Methods:The clinical data of 3 elderly patients with CNSL who received zanubrutinib combined regimens from July 2020 to March 2022 in the Affiliated Suzhou Hospital of Nanjing Medical University were retrospectively analyzed. Two of them were primary central nervous system lymphoma (PCNSL) and one was secondary central nervous system lymphoma (SCNSL). Relevant literature was reviewed at the same time.Results:The two patients with PCNSL were treated with zanubrutinib in combination with rituximab and lenalidomide (Z-R 2) regimen. One of them achieved complete remission (CR) after 6 cycles, and the other patient achieved partial remission (PR) after 1 cycle of Z-R 2 regimen. The patient with SCNSL was diagnosed with diffuse large B-cell lymphoma (DLBCL) previously and suffered from central nervous system relapse after achieving CR. The patient achieved PR after 2 cycles of Z-R 2 regimen, and then achieved CR followed by 4 cycles of zanubrutinib in combination with rituximab and high-dose methotrexate (Z-R-HD-MTX) regimen. Two of the three patients were still in CR until April 2022, and the longest disease-free survival time was 15 months. There were no severe adverse reactions during the treatment. Conclusions:Zanubrutinib combined regimens for 3 elderly patients with CNSL have shown promising effect and well tolerance, which may be considered as novel treatment for CNSL patients who are unable to tolerate severe chemotherapies or autologous hematopoietic stem cell transplantations.

Clinical Application of Zanubrutinib in B-Cell Lymphoma --Review / 中国实验血液学杂志

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.

Impact of China-US drug regulatory incentives on local innovative drug simultaneous development in multiple countries: An empirical study based on zanubrutinib / 中国临床药理学与治疗学

This article teases out the main regulatory incentives for innovative drugs in China and US, including optimizing the processes, setting time limits for registration, expedited programs, R&D and evaluation communication and receiving clinical data from overseas. Meanwhile, case study method is used to analyze the impact of these regulatory incentives on BeiGene's zanubrutinib, which is the first drug from Chinese Innovation Company simultaneously developed in US and China. The results show that regulatory incentives are key factors to realize simultaneous development of zanubrutinib by shortening the time of registration in both countries and reducing the costs and risks of drug development. Other domestic companies can learn from the experience of zanubrutinib, to target unmet clinical needs, to rationally use domestic and foreign regulatory policies, and to enhance communication with regulators. Domestic regulator also can provide more suggestion to companies who have the intention to develop products abroad, so that more innovative drugs developed by local companies can be on the world stage.

Bruton tyrosine kinase inhibitors and refractory mantle cell lymphoma / 中国临床药理学与治疗学

Bruton tyrosine kinase (BTK) is a key mediator of B-cell receptor signalling cascade and an effective target for treating mantle cell lymphoma (MCL). BTK inhibitors play a critical role in the treatment of MCL. Here we introduced the mechanism of action of BTKI in the treatment of MCL. Though generally well prescribed, Ibrutinib, as the first BTKI, still has limitations of toxicity and resistance. New BTK inhibitors, such as zanubrutinib, acalabrutinib and orelabrutinib, are designed to improve on the safety and efficacy as first-generation BTK inhibitors. Comparing the similarities and differences of the two generations of BTKI in structure and function provides a basis for better clinical application of BTKI. On November 15, 2019, FDA approved zanubrutinib for marketing for patients with adult mantle cell lymphoma. Compared with Ibrutinib, zanubrutinib was found with higher target selectivity, longer-lasting inhibition, fewer adverse reactions, and better patient benefit. Zanubrutinib provides a viable treatment option for patients with r/r MCL. At the same time, it is also actively carrying out clinical researches on the treatment of other B-cell lymphomas. It is a very promising targeted drug.