Mature B-Cell Neoplasm

U.S. label update includes superior progression-free survival results from the Phase 3 ALPINE head-to-head trial of BRUKINSA versus IMBRUVICA® (ibrutinib) in Relapsed or Refractory CLL ALPINE is the only Phase 3 Bruton’s tyrosine kinase (BTK) inhibitor trial to demonstrate superiority versus IMBRUVICA BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced the U.S. Food and Drug Administration (FDA) has approved a label update for BRUKINSA® (zanubrutinib) to include superior progression-free survival (PFS) results from the Phase 3 ALPINE trial comparing BRUKINSA against IMBRUVICA® (ibrutinib) in previously treated patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). “The ALPINE trial is the first and only study to demonstrate PFS superiority in a head-to-head comparison versus ibrutinib in CLL,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “BRUKINSA was approved in the U.S. for CLL at the beginning of 2023, and we submitted additional data from the ALPINE PFS analysis supporting it as the BTK inhibitor of choice in CLL, solidifying it as an important treatment option for patients. When making treatment decisions, it is critical that physicians and patients understand the totality of data supporting BRUKINSA’s robust efficacy and differentiated safety in CLL.” The updated label is based on a prespecified analysis of the ALPINE trial, which demonstrated superior efficacy and a favorable cardiac safety pro BRUKINSA versus ibrutinib in patients with R/R CLL and was presented in a late-breaking session at the 64th Annual American Society for Hematology (ASH) Meeting and Exposition and published simultaneously in The New England Journal of Medicine. The updated label includes data at a median follow-up of 31 months, in which BRUKINSA demonstrated superior PFS compared with ibrutinib in patients with R/R CLL (HR: 0.65 [95% CI, 0.49-0.86] P=.0024, for both investigator and independent review committee). Additionally, BRUKINSA demonstrated a favorable cardiac safety pro significantly lower rates of atrial fibrillation/flutter (5.2% vs. 13.3%) and zero deaths due to cardiac disorders with BRUKINSA versus six with ibrutinib (0% vs. 1.9%). Please see Important Safety Information below. At the recent 65th Annual ASH Meeting and Exposition, BeiGene presented extended follow-up data from the ALPINE trial at a median follow-up of 39 months. The data demonstrate that BRUKINSA continues to show sustained PFS benefit versus ibrutinib (HR: 0.68 [95% CI, 0.53-0.86] P=0.0011) among R/R CLL patients receiving more than three years of treatment, with durable PFS benefits observed across subgroups, including patients with 17p deletion or TP53 mutation (HR: 0.52 [95% CI, 0.33-0.83] P=0.0047). PFS benefit is consistent across multiple sensitivity analyses, demonstrating that PFS advantage with BRUKINSA was primarily driven by efficacy and not tolerability. The overall safety and tolerability pro consistent with previous ALPINE analyses, including persistently lower rates of cardiovascular events reported with BRUKINSA. The most commonly reported treatment emergent adverse events (≥20%) with BRUKINSA were COVID-19-related, neutropenia, hypertension, and upper respiratory tract infection. BRUKINSA is approved in more than 65 countries, including the U.S., China, EU, Great Britain, Canada, Australia, South Korea, and Switzerland, in selected indications and under development for additional indications globally. In the U.S., BRUKINSA is approved for the treatment of adult patients with CLL or small lymphocytic lymphoma, Waldenström’s macroglobulinemia, mantle cell lymphoma who have received at least one prior therapy, and relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based regimen. The global BRUKINSA development program includes more than 5,000 subjects enrolled to date in 29 countries and regions. About Chronic Lymphocytic Leukemia (CLL) A life-threatening cancer of adults, CLL is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.i,ii CLL is the most common type of leukemia in adults, accounting for about one-quarter of new cases of leukemia.ii,iii Approximately 18,740 new cases of CLL will be diagnosed in the United States in 2023.iii About BRUKINSA® (zanubrutinib) BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues. U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib) INDICATIONS BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with: Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) Waldenström’s macroglobulinemia (WM) Mantle cell lymphoma (MCL) who have received at least one prior therapy Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen The MCL and MZL indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION Warnings and Precautions Hemorrhage Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage, including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.6% of patients treated with BRUKINSA monotherapy in clinical trials, with fatalities occurring in 0.3% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 30% of patients. Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage. Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. Infections Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 24% of patients, most commonly pneumonia (11%), with fatal infections occurring in 2.9% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred. Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately. Cytopenias Grade 3 or 4 cytopenias, including neutropenia (22%), thrombocytopenia (8%) and anemia (7%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 11% of patients, and Grade 4 thrombocytopenia occurred in 2.8% of patients. Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed. Second Primary Malignancies Second primary malignancies, including non-skin carcinoma, have occurred in 13% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer reported in 7% of patients. Other second primary malignancies included malignant solid tumors (5%), melanoma (1.2%), and hematologic malignancies (0.5%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies. Cardiac Arrhythmias Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 3.7% of 1550 patients treated with BRUKINSA monotherapy, including Grade 3 or higher cases in 1.7% of patients. Patients with cardiac risk factors, hypertension and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.2% of patients. Monitor for signs and symptoms of cardiac arrhythmias (e.g. palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment. Embryo-Fetal Toxicity Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Adverse Reactions In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥30% of patients who received BRUKINSA (N=1550) included decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%). Drug Interactions CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily. CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers. Specific Populations Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily. Please see full U.S. Prescribing Information and U.S. Patient Information. About BeiGene BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit and follow us on LinkedIn and X (formerly known as Twitter). Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding whether BRUKINSA is the BTK inhibitor of choice in CLL and its importance as a treatment option for patients; the efficacy and safety pro BRUKINSA for patients with CLL; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law. IMBRUVICA® is a registered trademark of Pharmacyclics LLC and Janssen Biotech, Inc. i National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)–Patient Version. Accessed November 2023. . ii American Cancer Society. What is Chronic Lymphocytic Leukemia? Updated May 10, 2018. Accessed November 2023. . iii American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Updated January 12, 2023. Accessed November 2023. .

NEW YORK--(BUSINESS WIRE)-- Schrödinger (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, today announced that new data on SGR-1505, its investigational MALT1 inhibitor, and SGR-2921, its investigational CDC7 inhibitor, will be presented during a poster session at the American Society of Hematology (ASH) 65th Annual Meeting taking place virtually and in San Diego, California, December 9-12, 2023. Presentation of SGR-1505 data will include further characterization in preclinical oncology models as well as preliminary clinical biomarker information from the Phase 1 study in healthy subjects, which is nearing completion. The data support continued development of SGR-1505 as a potential therapy for patients with advanced B-cell malignancies, and a Phase 1 dose-escalation study in this patient population is ongoing. Additionally, data will be presented for SGR-2921 demonstrating strong anti-leukemic activity in preclinical models of acute myeloid leukemia (AML) representing difficult-to-treat disease. CDC7 is a cell cycle kinase in the DNA damage-response pathway and has emerged as a promising therapeutic target in oncology, including for the treatment of AML. Schrödinger recently initiated a Phase 1 dose-escalation study of SGR-2921 designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and recommended dose of SGR-2921 in patients with AML or myelodysplastic syndrome. Details of the data presentations are as follows: Title: SGR-1505 Is a Potent MALT1 Protease Inhibitor with a Potential Best-in-Class Pro /> Abstract number: 2997 Date & time: Sunday, December 10, 6:00 p.m. - 8:00 p.m. PDT Location: San Diego Convention Center, Halls G-H Title: SGR-2921, a Potent CDC7 Inhibitor, Demonstrates Significant Anti-Leukemic Responses in Patient-Derived AML Models Representing Difficult-to-Treat Disease Abstract number: 2801 Date & time: Sunday, December 10, 6:00 p.m. - 8:00 p.m. PDT Location: San Diego Convention Center, Halls G-H Additionally, the following clinical trial-in–progress posters will be presented for both SGR-1505 and SGR-2921: Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of SGR-1505 As Monotherapy in Subjects with Mature B-Cell Malignancies Abstract number: 3102 Date & time: Sunday, December 10, 6:00 p.m. - 8:00 p.m. PDT Location: San Diego Convention Center, Halls G-H Title: A First-in-Human, Phase 1, Dose Escalation Study of SGR-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Abstract number: 1548 Date & time: Saturday, December 9, 5:30 P.M. - 7:30 P.M. PDT Location: San Diego Convention Center, Halls G-H Schrödinger will review these data as part of its Pipeline Day, taking place virtually and in person on December 14, 2023. The company’s Pipeline Day will be a hybrid event, with limited in-person attendance available to members of the investment community, and a simultaneous webcast will be available for individual investors and other interested parties who wish to join virtually. The live presentation can be accessed in the “Investors” section of Schrödinger’s website and will be archived for approximately 90 days. To participate in the live webcast, please register for the event here. It is recommended that participants register at least 15 minutes in advance of the event. About Schrödinger Schrödinger is transforming the way therapeutics and materials are discovered. Schrödinger has pioneered a physics-based computational platform that enables discovery of high-quality, novel molecules for drug development and materials applications more rapidly and at lower cost compared to traditional methods. The software platform is licensed by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Schrödinger’s multidisciplinary drug discovery team also leverages the software platform to advance a portfolio of collaborative and proprietary programs to address unmet medical needs. Founded in 1990, Schrödinger has approximately 800 employees and is engaged with customers and collaborators in more than 70 countries. To learn more, visit , follow us on LinkedIn and Instagram, or visit our blog, Extrapolations.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 including, but not limited to those statements regarding the potential advantages of Schrödinger’s computational platform, the clinical potential and favorable properties of its product candidates, including SGR-1505 and SGR-2921, the potential for SGR-1505 to be used for the treatment of advanced B-cell malignancies, the potential for SGR-2921 to be used for the treatment of AML or myelodysplastic syndrome, and the timing, progress, and results of clinical trials for its product candidates. Statements including words such as “aim,” “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and statements in the future tense are forward-looking statements. These forward-looking statements reflect Schrödinger’s current views about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to the company and on assumptions the company has made. Actual results may differ materially from those described in these forward-looking statements and are subject to a variety of assumptions, uncertainties, risks and important factors that are beyond Schrödinger’s control, including the uncertainties inherent in drug development and commercialization, such as the conduct of research activities and the timing of and its ability to initiate and complete preclinical studies and clinical trials, whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials, uncertainties associated with the regulatory review of clinical trials and applications for marketing approvals and the ability to retain and hire key personnel on its business and other risks detailed under the caption “Risk Factors” and elsewhere in the company’s Securities and Exchange Commission filings and reports, including its Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2023, filed with the Securities and Exchange Commission on November 1, 2023, as well as future filings and reports by the company. Any forward-looking statements contained in this press release speak only as of the date hereof. Except as required by law, Schrödinger undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events, changes in expectations or otherwise.

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--( BUSINESS WIRE )--BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced the China National Medical Products Administration (NMPA) approved four applications for BRUKINSA (zanubrutinib), the company’s Bruton’s tyrosine kinase inhibitor (BTKi), including two Supplemental New Drug Applications for treatment-naïve adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and Waldenström's macroglobulinemia (WM), and two Supplemental Applications for conversions from conditional approval to regular approval. “These approvals further support BRUKINSA as the BTKi of choice in China for the treatment of B-cell malignancies such as CLL and WM,” said Lai Wang, Ph.D., Global Head of R&D at BeiGene. “We look forward to bringing people living with CLL and WM a new first-line treatment option as we work to support the Healthy China initiative and reduce global health inequity.” BRUKINSA previously received conditional approvals from NMPA for the treatment of adult patients with CLL/SLL and mantle cell lymphoma (MCL) who have received at least one prior therapy (R/R CLL/SLL and R/R MCL) in June 2020, and conditional approval for the treatment of adult patients with WM who have received at least one prior therapy (R/R WM) in June 2021. NMPA converted these conditional approvals to regular approvals for R/R CLL/SLL and R/R WM in April 2023. "CLL/SLL and WM patients are predominantly populated in the elderly, and there are increasing needs for improved efficacy and safety in CLL/SLL and WM treatments," said Professor Ma Jun, Director of the Harbin Institute of Hematology & Oncology, Chief Supervisor of Supervisory Committee at the Chinese Society of Clinical Oncology. “BRUKINSA has been recommended as the preferred regimen of multiple subtypes of lymphoma in both national and international guidelines i , ii , iii , iv , v . With these important approvals, BRUKINSA now becomes the only approved new-generation BTK inhibitor in China for the first-line treatment of adult CLL/SLL and WM patients, bringing healthcare providers in China with a new standard of care for their patients." The new approvals of BRUKINSA for CLL/SLL are supported by data from SEQUOIA (NCT03336333), in patients with previously untreated CLL/SLL. The new approvals of BRUKINSA for WM are based on data from ASPEN (NCT03053440), the first and only global Phase 3 head-to-head clinical trial of BTK inhibitors in WM. About Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) A slow-growing, life-threatening and incurable cancer of adults, CLL is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues vi , vii , viii . CLL is one of the most common types of leukemia, accounting for about one-quarter of new cases of leukemia ix . CLL and SLL are considered different manifestations of the same disease. Approximately 180 of every 100,000 people in China have CLL/SLL, accounting for 1% to 3% of all non-Hodgkin lymphoma cases x . About Waldenström’s Macroglobulinemia (WM) WM is a rare, slow-growing lymphoma that occurs in less than two percent of patients with non-Hodgkin’s lymphoma (NHL) xi . The disease usually affects older adults and is primarily found in the bone marrow, although it may also impact lymph nodes and the spleen xii . In China, there are an estimated 88,200 patients diagnosed with lymphoma each year. Approximately 91% of these cases are classified as NHL, amounting to ~1,000 newly diagnosed WM patients per year in China xiii, viii . About BRUKINSA ® (zanubrutinib) BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues. About BeiGene BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 9,400 colleagues spans five continents, with administrative offices in Basel; Beijing; and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential for BRUKINSA to become the BTKi of choice in China for patients with CLL or WM, and the benefits of such treatment for those patients; BeiGene’s efforts to make BRUKINSA more broadly available to patients in China and to reduce global health inequities;the future development and regulatory filing and approval of BRUKINSA in other markets; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates and achieve and maintain profitability; and the impact of the COVID-19 pandemic on BeiGene’s clinical development, regulatory, commercial, manufacturing, and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law. References i NCCN Guidelines. Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma. V2.2023. ii NCCN Guidelines. B-Cell Lymphomas.V2.2023. iii NCCN Guidelines. Waldenström Macroglobulinemia / Lymphoplasmacytic Lymphoma.V1.2023. iv CSCO 淋巴瘤诊疗指南 2023. v CSCO 恶性血液病诊疗指南 2023 vi National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Leukemia —Chronic Lymphocytic Leukemia (CLL). Accessed October 4,2021. https://seer.cancer.gov/statfacts/html/clyl.html vii Aster JC, Freedman A. Non-Hodgkin lymphomas and chronic lymphocytic leukemias. In: Aster JC, Bunn HF (eds.). Pathophysiology of Blood Disorders. 2nd ed. McGraw-Hill Education; 2017:chap 22. viii American Cancer Society. What is chronic lymphocytic leukemia? Updated May 10, 2018. Accessed December 6, 2020. https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html ix Yao Y, Lin X, Li F, Jin J, Wang H. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. Biomed Eng Online. 2022 Jan 11;21(1):4. doi: 10.1186/s12938-021-00973-6. PMID: 35016695; PMCID: PMC8753864. x https://mp.weixin.qq.com/s?__biz=MzA4ODQxMjgzNw==&mid=2654028680&idx=1&sn=af420ac7e860be0b26463c2e71c6e3f4&chksm=8bef6442bc98ed5477c5b17bb4973baa552611206f55c8c4b11ba9e7d7f032389914c3dcb45a&scene=27 xi Tam, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. October 2020. 136(18): 2038-2050. xii Lymphoma Research Foundation. Available at https://lymphoma.org/aboutlymphoma/nhl/wm/ . Accessed December 2020. xiii Chen, et al. Cancer statistics in China, 2015 [J]. CA: A Cancer Journal for Clinicians, 2016, 66(2):115-132.