Investigational New Drugs最新文献

Understanding the differentiation syndrome in acute promyelocytic leukemia: a comprehensive updated review. 了解急性早幼粒细胞白血病的辨证：一项全面的最新综述。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-25 DOI: 10.1007/s10637-025-01556-1

Nahed Damaj, Nadim Elias, Toufic Zeidan, Joseph Kattan

{"title":"Understanding the differentiation syndrome in acute promyelocytic leukemia: a comprehensive updated review.","authors":"Nahed Damaj, Nadim Elias, Toufic Zeidan, Joseph Kattan","doi":"10.1007/s10637-025-01556-1","DOIUrl":"https://doi.org/10.1007/s10637-025-01556-1","url":null,"abstract":"The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Differentiation syndrome (DS) is a common and potentially life-threatening condition that was initially described with the induction therapy of targeted agents in acute promyelocytic leukemia (APL). DS is typically marked by symptoms such as fever, difficulty breathing, low blood pressure, weight gain, fluid buildup in the pleural or pericardial cavities, and acute kidney failure. The incidence of DS in APL patients varies from 2 to 27% reflecting the discrepancies in diagnostic criteria, in various treatment protocols, and sometimes the use of preventive treatments. Corticosteroids, with or without cytoreductive therapy, should be initiated immediately upon suspicion of DS to mitigate related morbidity and mortality. In cases of severe DS, targeted anti-leukemic therapy should be halted. This review will cover the pathogenesis of DS, its clinical presentations, diagnostic criteria, management approaches, and the importance of implementing prospective tracking in clinical trials.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Research progress on cancer-related epigenetic switches. 癌症相关表观遗传开关的研究进展。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-13 DOI: 10.1007/s10637-025-01555-2

Chunyu Yu, Jie Sun, Jinlong Tong, Ziqing Xu, Qijia Zhang

引用次数: 0

Clinical characterizations, management, and prognosis in immune checkpoint inhibitor-induced myelitis. 免疫检查点抑制剂诱导的脊髓炎的临床特征、管理和预后。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-09 DOI: 10.1007/s10637-025-01553-4

Yi-Xiao Li, Rui-Yun Wang, Zhi-Hang Lu, Wei-Cong Zhang, Yong-Jian Wang, Ming Meng, Yan-Lei Hao

{"title":"Clinical characterizations, management, and prognosis in immune checkpoint inhibitor-induced myelitis.","authors":"Yi-Xiao Li, Rui-Yun Wang, Zhi-Hang Lu, Wei-Cong Zhang, Yong-Jian Wang, Ming Meng, Yan-Lei Hao","doi":"10.1007/s10637-025-01553-4","DOIUrl":"https://doi.org/10.1007/s10637-025-01553-4","url":null,"abstract":"The expanding clinical application of immune checkpoint inhibitors (ICIs) has led to increasing recognition of neurological immune-related adverse events, among which myelitis represents a rare but clinically significant complication. Currently, most available data come from case reports or small case series, highlighting the need for comprehensive characterization. Our study systematically analyzed the clinical features of ICI-induced myelitis to improve diagnostic and therapeutic approaches. Through a comprehensive literature review up to February 28, 2025, we identified and analyzed 36 cases of ICI-associated myelitis from 27 publications. The study cohort had a median age of 58 years (range 16-81) with male predominance (58.3%). Clinical presentations included isolated myelitis (63.9%) and multifocal neurological involvement (36.1%), most commonly manifesting meningoencephalomyelitis/encephalomyelitis. The median time to symptom onset was 2 months (range 0.3-8) after treatment initiation, with a median of 4 treatment cycles (range 1-51). The most frequently associated malignancies were melanoma and lung cancer, with programmed cell death protein-1 inhibitor being the most commonly used regimen (69.4%). Diagnostic evaluation revealed longitudinally extensive spinal cord lesions (≥ 3 vertebral segments) in 75.0% of patients, along with frequent inflammatory cerebrospinal fluid abnormalities. Neural autoantibodies were detected in 33.3% of cases. Treatment strategies predominantly involved corticosteroids (97.2%) and ICI discontinuation (91.7%). While most patients (72.2%) showed improvement, relapses occurred in 30.6% of cases. These findings emphasize the importance of early recognition and prompt immunosuppressive therapy for ICI-induced myelitis.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical features, treatment, and outcomes of anti-PD-L1 induced psoriasis. 抗pd - l1诱导的银屑病的临床特征、治疗和结局。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-06 DOI: 10.1007/s10637-025-01554-3

Jian Xiao, Zhi Xia, Zhu Wu, Min Fang

{"title":"Clinical features, treatment, and outcomes of anti-PD-L1 induced psoriasis.","authors":"Jian Xiao, Zhi Xia, Zhu Wu, Min Fang","doi":"10.1007/s10637-025-01554-3","DOIUrl":"https://doi.org/10.1007/s10637-025-01554-3","url":null,"abstract":"Background: This study focuses on rare immune-mediated psoriasis induced by anti-PD-L1 drugs. Given that its clinical features have not been fully defined, the aim is to clarify the clinical manifestations, treatment, and outcomes of anti-PD-L1-induced psoriasis.Methods: We performed a retrospective analysis of psoriasis cases induced by anti-PD-L1 agents. The study involved systematically retrieving case reports from relevant databases up to April 23, 2025, for comprehensive evaluation.Results: This study included 31 patients, with 90.2% being male and a median age of 65 years (40-81 years). The anti-PD-L1 agents administered to patients included atezolizumab, durvalumab, and avelumab. Notably, 16 patients (51.6%) developed de novo psoriasis. The median time to psoriasis onset after drug initiation was 54.5 days (7-690 days), with plaque psoriasis being the most common clinical type (54.8%). In terms of treatment strategies, 19 patients (61.3%) discontinued anti-PD-L1 therapy, while 8 patients (25.8%) continued treatment. Following clinical interventions, including primarily the administration of topical steroids, symptomatic improvement or complete remission was reported in 25 patients (80.6%).Conclusion: When administering anti-PD-L1 agents, close monitoring for the onset of psoriatic symptoms in patients is essential to ensure timely detection and diagnosis. For patients who have been diagnosed with psoriasis, appropriate measures should be taken based on their specific clinical conditions, such as discontinuing anti-PD-L1 therapy or administering psoriasis treatment medications.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated triple-negative breast Cancer. 一种新的CDK4抑制剂用于化疗治疗的三阴性乳腺癌的髓细胞保护。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-06 DOI: 10.1007/s10637-025-01550-7

Ava Safaroghli-Azar, Laychiluh B Mekonnen, Ramin Hassankhani, Jimma Lenjisa, Sunita Kc Basnet, Hajer Batayneh, Muhammed H Rahaman, Shudong Wang

{"title":"A novel CDK4 inhibitor for myeloid protection in chemotherapy-treated triple-negative breast Cancer.","authors":"Ava Safaroghli-Azar, Laychiluh B Mekonnen, Ramin Hassankhani, Jimma Lenjisa, Sunita Kc Basnet, Hajer Batayneh, Muhammed H Rahaman, Shudong Wang","doi":"10.1007/s10637-025-01550-7","DOIUrl":"https://doi.org/10.1007/s10637-025-01550-7","url":null,"abstract":"Background: Despite advances in cancer treatment, chemotherapy remains a cornerstone of clinical practice. However, its efficacy is often compromised by dose-limiting haematologic toxicities. Recent strategies aim to enhance chemotherapy tolerability while preserving its effectiveness. One emerging approach involves selective CDK4 inhibitors to serve as myeloid-protective agents in retinoblastoma (RB)-negative tumours, such as triple-negative breast cancer (TNBC). Because bone marrow (BM) cells rely on RB for proliferation, CDK4 inhibitors may protect these cells while sparing RB-deficient tumour cells. The present study investigated the potential of AU2-94, a first-in-class CDK4 inhibitor, to protect BM cells during myelosuppressive chemotherapy in TNBC, beyond its established application in RB-positive cancers.Methods: This study employed in vitro, ex vivo, and in vivo experiments to evaluate the myeloid-protective effects of AU2-94 against chemotherapy-induced damage.Results: AU2-94 induced a transient G1 arrest that protects BM cells from chemotherapy-induced apoptosis by preventing DNA double-strand breaks. Pre-treatment with AU2-94 prior to 5-fluorouracil (5-FU) administration reduced BM cells apoptosis, preserved Ki67-positive cells, and mitigated declines in red blood cells and neutrophils. Similarly, AU2-94 pre-treatment before cisplatin administration reduced cisplatin-induced haematologic toxicity in RB-deficient TNBC bearing mice without compromising the efficacy of chemotherapy.Conclusion: These findings support the repurposing of AU2-94 as a myeloprotective agent, highlighting its therapeutic potential in RB-deficient tumours. With AU2-94 advancing to clinical trials, these results underscore its broader therapeutic promise, extending to both RB-positive and RB-negative cancer treatment.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Approval of high-benefit oncology drugs in Japan: utilization of expedited regulatory pathways for the accelerated approved anticancer drugs. 日本高效益肿瘤药物的批准：加速批准抗癌药物的加速监管途径的利用。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-04 DOI: 10.1007/s10637-025-01549-0

Ayumi Taguchi, Naoki Matsumaru, Katsura Tsukamoto

{"title":"Approval of high-benefit oncology drugs in Japan: utilization of expedited regulatory pathways for the accelerated approved anticancer drugs.","authors":"Ayumi Taguchi, Naoki Matsumaru, Katsura Tsukamoto","doi":"10.1007/s10637-025-01549-0","DOIUrl":"https://doi.org/10.1007/s10637-025-01549-0","url":null,"abstract":"Early access to promising new drugs with superior efficacy compared to existing treatments is globally sought after. To facilitate such access, regulatory authorities in each country have implemented special regulatory measures that expedite drug approval. This study examined the approval lag of anticancer drugs granted accelerated approval (AA) by the U.S. Food and Drug Administration (FDA) and their corresponding approval timelines in Japan. Additionally, we assessed the use of expedited regulatory pathways in Japan. Our analysis included 55 anticancer drugs that received AA from the FDA between 2012 and 2021 and evaluated their approval in Japan through 2022. The median approval lag was 649 days, primarily attributable to submission delays. Drugs for which Japan participated in the pivotal FDA study and the use of expedited regulatory pathways in Japan had significantly shorter approval lags (P < 0.001 and P = 0.0172, respectively). However, the utilization of the recently implemented conditional early approval system was limited. Although AA anticancer drugs are often approved based on early clinical trial data, our findings highlight that participation in pivotal studies is crucial for minimizing approval delays in Japan. Despite improvements in drug approval timelines, substantial delays persist, underscoring the need for more effective utilization of expedited regulatory pathways. Enhancing collaboration in early-stage clinical trials and optimizing regulatory processes may facilitate faster access to high-benefit anticancer therapies in Japan.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A phase I study of liposomal Irinotecan (ONIVYDE®) in combination with TAS-102 (LONSURF®) in refractory solid tumors. 伊立替康脂质体（ONIVYDE®）联合TAS-102 （LONSURF®）治疗难治性实体瘤的I期研究

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-06-04 DOI: 10.1007/s10637-025-01547-2

Nai-Jung Chiang, Li-Yuan Bai, I-Wei Ho, Chih-Hung Hsu, Yi-Hsin Liang, Chang-Fang Chiu, Ching-Chan Lin, Kwang-Yu Chang, Shang-Hung Chen, Hui-Jen Tsai, Yu-Ping Lin, Li-Tzong Chen, Chia-Chi Lin

{"title":"A phase I study of liposomal Irinotecan (ONIVYDE®) in combination with TAS-102 (LONSURF®) in refractory solid tumors.","authors":"Nai-Jung Chiang, Li-Yuan Bai, I-Wei Ho, Chih-Hung Hsu, Yi-Hsin Liang, Chang-Fang Chiu, Ching-Chan Lin, Kwang-Yu Chang, Shang-Hung Chen, Hui-Jen Tsai, Yu-Ping Lin, Li-Tzong Chen, Chia-Chi Lin","doi":"10.1007/s10637-025-01547-2","DOIUrl":"https://doi.org/10.1007/s10637-025-01547-2","url":null,"abstract":"Onivyde, a liposome-encapsulated irinotecan, is used for advanced pancreatic, while TAS-102 (trifluridine/tipiracil) is indicated for metastatic colorectal and gastric cancers. This study aims to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), and safety profiles of liposomal irinotecan combined with TAS-102. This multicenter, phase I study utilized a 3 + 3 dose-escalation design. Patients with treatment-refractory solid malignancies received free base liposomal irinotecan at 50-70 mg/m2 on Day 1 and TAS-102 at 25-35 mg/m2 twice daily on Days 1-5 of a 14-day cycle. Patients homozygous for UGT1A1*28 (TA7/TA7), UGT1A1*6 (A/A), or double heterozygous (TA6/TA7 and G/A) alleles were excluded. Prophylactic G-CSF was allowed. Twenty-six evaluable patients were enrolled across seven dose levels of liposomal irinotecan (free-base)/TAS-102 combination: 3 patients each at level 1 (50/25 mg/m2), level 2A (60/25 mg/m2), level 2B (50/30 mg/m2), and level 3 (60/30 mg/m2); 6 at level 4A (70/30 mg/m2); 3 at level 4B (60/35 mg/m2); and 5 at level 5 (70/35 mg/m2). An additional 15 patients were enrolled in the expansion cohort at the MTD of 70/30 mg/m2 (level 4A), designated as the RP2D. Overall grade 3-4 treatment-related adverse events occurred in 44.2% of 43 all treated patients, with neutropenia (16.3%), diarrhea (14%), and fatigue (11.6%). Partial responses were observed in 18.4% of patients, predominantly in neuroendocrine tumor, gastric and esophageal carcinomas. The combination of liposomal irinotecan and TAS-102 at the RP2D of 70/30 mg/m2 demonstrated acceptable safety and promising efficacy in refractory solid tumors, warranting further investigation.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of orelabrutinib combined with rituximab and high dose methotrexate in primary or secondary central nervous system diffuse large B-cell lymphoma: a retrospective analysis. orelabrutinib联合rituximab和高剂量甲氨蝶呤治疗原发性或继发性中枢神经系统弥漫性大b细胞淋巴瘤的疗效和安全性：回顾性分析。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-05-31 DOI: 10.1007/s10637-025-01542-7

Jiahao Zhou, Lingxiao Xing, Yi Miao, Shuchao Qin, Run Zhang, Hanning Tang, Wei Xu, Yi Xia, Huayuan Zhu, Jianyong Li

{"title":"Efficacy and safety of orelabrutinib combined with rituximab and high dose methotrexate in primary or secondary central nervous system diffuse large B-cell lymphoma: a retrospective analysis.","authors":"Jiahao Zhou, Lingxiao Xing, Yi Miao, Shuchao Qin, Run Zhang, Hanning Tang, Wei Xu, Yi Xia, Huayuan Zhu, Jianyong Li","doi":"10.1007/s10637-025-01542-7","DOIUrl":"https://doi.org/10.1007/s10637-025-01542-7","url":null,"abstract":"Central nervous system lymphoma (CNSL) are mainly diffuse large B-cell lymphomas (DLBCLs). Orelabrutinib is a second-generation Bruton's tyrosine kinase (BTK) inhibitor and has shown single-agent activity in CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib combined with rituximab and high dose methotrexate (ORM) regimen in the treatment of patients with CNSL. We retrospectively analyzed data from CNSL patients treated with ORM regimen at Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University from April 2021 to October 2023. Patients receiving rituximab plus high-dose methotrexate (RM regimen) from June 2017 to January 2024 were identified as the control group. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A total of 32 patients were identified: 14 patients in the ORM group and 18 in the RM group. CR rates were 84.6% in the ORM group and 44.4% in the RM group (P = 0.032). Median PFS was 18.6 months in the RM group and 26.3 months in the ORM group (P = 0.133). Median OS was 34.1 months in the RM group and has not yet been reached in the ORM group (P = 0.041). Patients in the ORM group showed a higher 2-year OS rate than those in the RM group (82.1% vs. 57.5%). No grade 5 AE was reported in both groups. The incidence of grade 3-4 AE was comparable between the two treatment groups. ORM regimen was effective and well-tolerated in patients with CNSL. This combination therapy provides a new potential therapeutic strategy for patients with CNSL.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The recombinant anti-MET/EpCAM bispecific antibody fragment: a promising novel therapeutic approach for breast cancer treatment. 重组抗met /EpCAM双特异性抗体片段：一种有前景的乳腺癌治疗新方法。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-05-30 DOI: 10.1007/s10637-025-01546-3

Roya Mirzaei, Mohammadreza Azimi, Soroush Karimi, Mahshid Seyed Karimi, Seyed Ali Mir Aghel, Malihe Salehi, Neda Jalili, Fatemeh Yadegari, Leila Farahmand

{"title":"The recombinant anti-MET/EpCAM bispecific antibody fragment: a promising novel therapeutic approach for breast cancer treatment.","authors":"Roya Mirzaei, Mohammadreza Azimi, Soroush Karimi, Mahshid Seyed Karimi, Seyed Ali Mir Aghel, Malihe Salehi, Neda Jalili, Fatemeh Yadegari, Leila Farahmand","doi":"10.1007/s10637-025-01546-3","DOIUrl":"https://doi.org/10.1007/s10637-025-01546-3","url":null,"abstract":"Our study aims to target Met and EpCAM to inhibit angiogenesis in breast cancer, particularly triple-negative breast cancer (TNBC). We have developed a new bispecific antibody that targets both MET and EpCAM, which are commonly overexpressed in tumor cells. This antibody aims to reduce tumor cell proliferation and spread. After cloning and expressing the anti-Met/EPCAM sequence in Escherichia coli, we confirmed its accuracy through Western blot analysis. Flow cytometry indicated its binding activities to MET and EPCAM on MDA-MB-231 and MCF-7 cell lines. Our antibody showed anti-proliferative potential as indicated by apoptosis and MTT assay, leading to the inhibition of migration and invasion in breast cancer cell lines. After conducting a thorough analysis of cytokine production, we discovered that our bispecific antibody effectively influenced the levels of IL-8 and IL-6. These cytokines play crucial roles in angiogenesis and the progression of breast cancer. These findings indicate that our bispecific antibody holds promise as a potential therapy for triple-negative breast cancer. It has the potential to impede the formation of new blood vessels in tumors, thus restraining their growth and spread.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Orelabrutinib combined with rituximab and high-dose methotrexate as induction therapy in newly diagnosed primary central nervous system lymphoma. 奥瑞布替尼联合利妥昔单抗和大剂量甲氨蝶呤诱导治疗新诊断的原发性中枢神经系统淋巴瘤。

IF 3 3区医学

Investigational New Drugs Pub Date : 2025-05-27 DOI: 10.1007/s10637-025-01548-1

Xi-Bin Xiao, Yi-Qin Weng, Hua-Wei Jiang, Xian Li, Jing Xie, Chang-Qian Bao, Wen-Bin Qian

{"title":"Orelabrutinib combined with rituximab and high-dose methotrexate as induction therapy in newly diagnosed primary central nervous system lymphoma.","authors":"Xi-Bin Xiao, Yi-Qin Weng, Hua-Wei Jiang, Xian Li, Jing Xie, Chang-Qian Bao, Wen-Bin Qian","doi":"10.1007/s10637-025-01548-1","DOIUrl":"https://doi.org/10.1007/s10637-025-01548-1","url":null,"abstract":"Objective: Limited treatment options for primary central nervous system lymphoma (PCNSL) highlight the need for alternative therapies. This study evaluated orelabrutinib (O) and rituximab (R), plus high-dose methotrexate (M) (ORM), as a potential induction therapy for newly diagnosed PCNSL.Methods: Patients received six cycles of 150 mg/day orelabrutinib, 375 mg/m2 rituximab, plus 3.5 g/m2 methotrexate every 3 weeks, followed by autologous hematopoietic stem cell transplantation and orelabrutinib maintenance. The primary endpoint was the overall response rate (ORR) at the end of induction therapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.Results: From October 21, 2020, to October 22, 2024, 28 patients were treated and evaluated for efficacy and safety analyses. At the end of induction therapy, the ORR was 71.4% (95% CI, 51.3-86.8), including 16 (57.1%) complete and 4 (14.3%) partial responses. At a median follow-up of 21.6 months, the median PFS was 35.3 months (95% CI, 8.4-not evaluable), and the median OS was not reached, with PFS and OS rates of 64.3% and 96.3% at 1 year, 64.3% and 90.9% at 2 years, and 45.9% and 82.7% at 3 years, respectively. All 28 (100%) patients experienced treatment-related adverse events (TRAEs) of any grade. Grade 3 TRAEs occurred in seven (25.0%) patients, including five (17.9%) leukopenia, one (3.6%) thrombocytopenia, and one (3.6%) diarrhea. No other Bruton's tyrosine kinase inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) or TRAE-related deaths were observed.Conclusion: The ORM induction regimen showed anti-tumor activity with a favorable safety profile, offering a potential therapeutic strategy for newly diagnosed PCNSL.Clinical trial registration: ClinicalTrials.gov: NCT05600660.","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0