On January 1, 2026, the new version of the National Reimbursement Drug List officially came into effect. Orelabrutinib (Yinokai®), a novel BTK inhibitor independently developed by Innovent Biologics, has rapidly achieved medical insurance coverage for first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, commonly known as "CLL"), benefiting more patients. On January 17, during the working meeting of the Chinese Society of Clinical Oncology (CSCO) Expert Committee on Leukemia, Lymphoma and Myeloma and the 2026 CSCO Hematologic Oncology Academic Conference held in Haikou, the "Press Conference on the Implementation of Orelabrutinib 1L CLL/SLL Indication Under Medical Insurance Coverage" was successfully held. Several leading experts in the field of lymphoma gathered at the event, including Professor Ma Jun from the Harbin Institute of Hematology and Oncology, Professor Li Jianyong from Jiangsu Provincial People's Hospital, Professor Qiu Lugui from the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences, Professor Mi Jianqing from Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Professor Zhang Wei from Peking Union Medical College Hospital, and Professor Zhu Huayuan from Jiangsu Provincial People's Hospital. They engaged in in-depth discussions on the current status of chronic lymphocytic leukemia (CLL) diagnosis and treatment, the clinical significance of orelabrutinib's inclusion in medical insurance coverage, and shared the latest research findings in the field.

It is worth noting that orelabrutinib already has three lymphoma-related indications covered by medical insurance: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has received at least one prior therapy, mantle cell lymphoma (MCL) that has received at least one prior therapy, and marginal zone lymphoma (MZL) that has received at least one prior therapy, broadly covering multiple clinical scenarios for lymphoma treatment.

In addition, a nationwide, multicenter, large-sample prospective real-world study (OBaC study) is actively advancing its large-scale patient enrollment. Led by Professors Li Jianyong, Qiu Lugui, and Mi Jianqing, this study aims to systematically evaluate the efficacy and safety of orelabrutinib in treating treatment-naïve chronic lymphocytic leukemia (CLL) patients in the real world, and further compare the impact of continuous and limited-term treatment strategies on patient outcomes. The study was successfully launched in November 2025 and plans to enroll 400 treatment-naïve CLL patients at 27 centers nationwide, with enrollment expected to be completed by the end of 2027.

The inclusion of a new BTK inhibitor in medical insurance coverage will help accelerate the transition of chronic lymphocytic leukemia (CLL) treatment into a "chemotherapy-free era."

Chronic lymphocytic leukemia (CLL) is a B-cell hematologic malignancy that is prevalent in the elderly. The "Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Tumor (2022)" show that the median age of onset for CLL in China is 65 years, with a significantly lower incidence rate than in Europe and the United States. Furthermore, the incidence rate is increasing with population aging and improved diagnostic capabilities, posing a serious threat to the health and lives of the middle-aged and elderly population.

The rise of targeted therapy has completely changed the treatment paradigm for chronic lymphocytic leukemia (CLL), with novel BTK inhibitors, represented by orelabrutinib, leading CLL treatment into a faster "chemotherapy-free era." A phase III study of orelabrutinib as first-line treatment for CLL showed that after 12 months of treatment, the progression-free survival (PFS) rate reached 93.1%, and after 18 months of treatment, the overall survival (OS) rate was as high as 96.7%.

The first-line indication for orelabrutinib for chronic lymphocytic leukemia was included in medical insurance at the end of 2025 and implemented on January 1, 2026, which means that this innovative therapy has achieved a key leap from "available" to "accessible" for the majority of patients.

Professor Ma Jun of the Harbin Institute of Hematology and Oncology stated: "Chronic lymphocytic leukemia (CLL) is an incurable subtype of B-cell non-Hodgkin's lymphoma, with a 5-year relative survival rate of approximately 65.1%-88.5%, and a high relapse rate. First-generation BTK inhibitors face challenges such as limited deep remission rates with single-agent therapy, low complete remission (CR) rates, and a relatively high risk of adverse events (AEs). The novel BTK inhibitor orelabrutinib has shown promising data in treating treatment-naïve CLL/SLL patients, achieving a CR rate as high as 12.1%, while also exhibiting better safety. Based on this, orelabrutinib was approved for marketing as a first-line treatment for CLL in 2025 and listed as a first-line treatment for CLL in the 2025 edition of the CSCO Lymphoma Diagnosis and Treatment Guidelines." Level I recommendation. Meanwhile, the industry is exploring chemotherapy-free combination regimens based on BTK inhibitors, such as orelabrutinib combined with the novel BCL2 inhibitor Mesutoclax, which could potentially lead to deeper remissions or even limited-cycle treatment, thus contributing to the development of more personalized and precise CNL treatment. The renewal of orelabrutinib's previous indications under medical insurance and its inclusion in first-line CNL treatment under medical insurance can reduce the financial burden on patients, enabling more patients to benefit from this highly effective and precise treatment option. It is also expected to accelerate the shift of first-line CNL treatment from 'chemotherapy/immunotherapy' to a 'chemotherapy-free' model.

Level I recommendation in guidelines sets a new benchmark for first-line treatment.

The core advantage of orelabrutinib lies not only in its significant survival benefits but also in its ability to help patients achieve a deeper treatment goal: "deep remission"—the key to long-term disease control and reducing the risk of relapse. In the registration study of orelabrutinib as first-line treatment for chronic lymphocytic leukemia (CLL), approximately 12.1% of patients achieved "complete remission ," and the proportion of patients achieving deep remission continued to increase with prolonged treatment , laying a crucial foundation for long-term stable survival. The 2025 edition of the CSCO Lymphoma Diagnosis and Treatment Guidelines lists orelabrutinib as a Grade I recommendation for first-line CLL treatment.

Professor Li Jianyong of Jiangsu Provincial People's Hospital stated: "The inclusion of orelabrutinib in the medical insurance coverage for first-line treatment of chronic lymphocytic leukemia (CLL) will bring new hope to CLL patients. Data from a Phase III registration study of orelabrutinib led by our center, which included 192 treatment-naïve CLL patients, showed a complete response (CR) rate of 12.1% at a median follow-up of 21.4 months, with low incidences of cardiovascular events, bleeding, infection, diarrhea, and rash. Furthermore, orelabrutinib allows for once-daily oral administration, improving treatment convenience and patient compliance, and facilitating continued treatment. Orelabrutinib has also demonstrated good efficacy and safety in the treatment of relapsed/refractory CLL patients. A registration study of orelabrutinib monotherapy for relapsed/refractory CLL patients showed that with continued treatment, patient remission deepened, reaching a CR rate of 26.3% at a median follow-up of 33.1 months , with a discontinuation rate of only 7.5% and an incidence of grade 3 or higher atrial fibrillation/flutter of 0%. This positive performance lays a solid evidence-based foundation for expanding orelabrutinib into first-line treatment."

Combination therapy shows potential; China's largest real-world study with the largest sample size embarks.

Orelabrutinib is continuously reshaping the treatment landscape of chronic lymphocytic leukemia (CLL). In addition to its excellent performance as a first-line monotherapy, its combination therapy regimens also demonstrate significant potential. Data presented at the 2025 American Society of Hematology (ASH) Annual Meeting showed that orelabrutinib, combined with Mesutoclax, a BCL2 inhibitor independently developed by Innovent Biologics, demonstrated excellent safety and efficacy in both treatment-naïve and relapsed/refractory CLL patients (including those who failed previous BTK inhibitor therapy). Its significant efficacy and deep remission promise to bring hope of clinical cure to first-line CLL/SLL patients.

Professor Qiu Lugui of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, stated: "In recent years, Chinese scholars have conducted numerous exploratory studies on orelabrutinib combination therapy, accumulating rich evidence-based data for its expanded clinical application. For example, a study on orelabrutinib combined with the novel BCL2 inhibitor Mesutoclax for the treatment of treatment-naïve chronic lymphocytic leukemia was reported at the 2025 ASH Annual Meeting. The results showed that the overall response rate (ORR) in the orelabrutinib combined with Mesutoclax 125 mg dose group reached 100%." At week 36 of combined therapy, the negative rate of minimal residual disease (MRD) in peripheral blood was 65%; the 12-month progression-free survival (PFS) rate was 100%. Another phase II clinical trial conducted by Chinese researchers, using orelabrutinib + bendamustine + oxutuzumab (OBG regimen) as first-line treatment for unfit chronic lymphocytic leukemia without 17p-/TP53 mutations, showed that at the end of 7 cycles, 72.7% of patients achieved complete remission (CR), with an objective response rate (ORR) of 100% and a 100% negative rate of MRD in peripheral blood. These two studies demonstrate that orelabrutinib, whether combined with novel targeted therapies or immunochemotherapy, can achieve a high rate of CR in patients. Furthermore, no BTK inhibitor-related cardiovascular events or bleeding risks were observed in the studies, confirming the favorable safety profile of orelabrutinib.

Professor Zhu Huayuan of Jiangsu Provincial People's Hospital stated: "Our center led a phase II clinical trial of orelabrutinib + fludarabine + cyclophosphamide + octotuzumab (OFCG) for the treatment of newly diagnosed chronic lymphocytic leukemia (CLL) patients. Results showed that the MRD-guided orelabrutinib combination regimen delivered deep remission and good survival rates, with remission deepening as treatment progressed: With a median follow-up of 21.4 months, the peripheral blood MRD-negative rate, bone marrow MRD-negative rate , and CR/complete remission with incomplete hematologic recovery (CRi) rate were 95%, 91%, and 77% in the 22 patients who completed 12 cycles , respectively ; the two-year progression-free survival (PFS) rate was 96%, and no cardiovascular events such as atrial fibrillation/atrial flutter occurred during the period. Based on this study, for young, chemotherapy-tolerant (fit) newly diagnosed CLL patients, regardless of whether they have IGHV or TP53 mutations, the MRD-guided OFCG limited-term treatment regimen can deliver faster and deeper remission and the possibility of discontinuing treatment."

Professor Mi Jianqing of Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, pointed out: "As a new generation BTK inhibitor, orelabrutinib has undergone structural optimization based on the first generation BTK inhibitors, giving it optimal kinase selectivity, which helps reduce off-target effects and makes orelabrutinib have better efficacy and safety. We have conducted multiple clinical trials of orelabrutinib monotherapy for B-cell malignancies. Studies have shown that with continuous orelabrutinib treatment, no ≥3 grade atrial fibrillation/atrial flutter or other arrhythmias were observed, and most adverse reactions could be resolved with corresponding supportive treatment. I am currently leading a prospective, multicenter, non-interventional real-world study with Professors Li Jianyong and Qiu Lugui, hoping to produce high-quality clinical evidence as soon as possible to make a substantial contribution to optimizing the treatment strategy for chronic lymphocytic leukemia and improving patient survival benefits."

Breaking the treatment bottleneck of BTK inhibitors and extending hope for survival for patients who are refractory or intolerant.

For patients who cannot continue to benefit from their original BTK inhibitor therapy due to intolerance or poor efficacy, finding effective and safe follow-up options is a pressing clinical challenge. Switching to the highly selective BTK inhibitor orelabrutinib is emerging as a key pathway. Studies show that orelabrutinib can reduce off-target toxicities while maintaining good efficacy and achieving deeper remission.

Professor Zhang Wei from Peking Union Medical College Hospital explained , “Our center conducted a single-center retrospective study, primarily evaluating the efficacy and safety of orelabrutinib in treating CLL/SLL in the real world. The study included 63 patients, including treatment-naïve patients and those who discontinued previous treatment due to disease progression or intolerance to adverse reactions. Among them, 31 patients previously using ibrutinib/zanubrutinib switched to orelabrutinib, achieving an ORR of 83.9% and a disease control rate (DCR) of 96.8%. More importantly, 48.4% of patients experienced improved remission , including 6 patients who previously only achieved stable disease (SD) and achieved partial remission (PR) after switching to orelabrutinib , and 8 patients who previously achieved partial remission (PR) or SD and achieved CR. Patients with resistance or intolerance all benefited. Regarding safety, 82.9% of patients experienced a resolution of adverse events (AEs), 14.6% experienced a mitigation of adverse events, and no grade ≥3 AEs occurred.”

A real-world study conducted by Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, evaluated the efficacy and safety of orelabrutinib in treating indolent non-Hodgkin lymphoma intolerant to prior BTK inhibitors. The study included 66 patients, 42 of whom were chronic lymphocytic leukemia (CLL). After switching to orelabrutinib, 11 CLL patients achieved complete remission (CR), and 25 achieved partial remission (PR) or partial remission with elevated lymphocytes (PR-L). At a median follow-up of 6.8 months, both progression-free survival (PFS) and overall survival (OS) were 100%. Adverse events were resolved or alleviated in 76.8% of patients.

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