Pentostatin

点击蓝字，关注我们 编者按：近年来，随着消化道肿瘤治疗手段不断演进，化疗、免疫治疗及抗体偶联药物（ADC）等新模式广泛应用，化疗相关中性粒细胞减少（CIN）及发热性中性粒细胞减少（FN）的管理重要性进一步凸显。与此同时，2026年长效粒细胞集落刺激因子（G-CSF）医保限定范围进一步拓宽至“既往化疗曾发生重度中性粒细胞减少的患者”，为临床更早识别高危人群、实施规范预防提供了更有力的政策支撑。围绕消化道肿瘤领域CIN/FN管理现状、新版医保政策要点及临床用药选择，《肿瘤瞭望》特别邀请河北医科大学第四医院殷飞教授进行深入解读。 01 《肿瘤瞭望》：殷教授您好，在消化道肿瘤领域，当前我国CIN/FN的管理现状如何？您认为临床最需要关注和提升的地方是什么？ 殷飞教授 河北医科大学第四医院 从整体疾病谱来看，我国是消化道肿瘤大国，胃癌、食管癌、结直肠癌、胰腺癌等都具有较高的发病和死亡负担。在这样的背景下，化疗仍然是消化道肿瘤治疗中的基础性手段之一，而CIN和FN则是临床中最常见、也最容易影响治疗连续性的并发症之一。 既往针对实体瘤患者的大样本研究提示，3~4级CIN在胃癌、食管癌和结直肠癌中的发生率并不低，这也说明在消化道肿瘤领域，CIN/FN管理绝不是一个边缘问题，而是直接关系到治疗质量和患者获益的重要问题。更值得重视的是，CIN/FN带来的影响并不只是实验室指标异常。很多患者一旦出现明显粒细胞下降，就可能被迫延迟治疗、下调剂量，甚至中断既定方案。临床上常见的情况是，患者因此延迟7~10天接受下一周期治疗，或者被迫降低剂量强度。表面上看似只是治疗节奏稍有改变，但如果累计导致相对剂量强度（RDI）下降，最终可能影响肿瘤控制效果，甚至影响总生存期（OS）。 此外，随着治疗模式升级，CIN/FN防治压力也在加大。比如在食管癌、胃癌等疾病中，免疫联合化疗已经越来越常见；再比如抗体偶联药物（ADC）也可能叠加血液学毒性。因此，我认为当前最需要提升的，一是对CIN/FN危害的整体认识，不能把它简单理解为“白细胞低一点”；二是要强化基于风险评估的预防思维，把管理关口适当前移；三是要让指南和共识真正落实到临床路径中。 02 《肿瘤瞭望》：面对这样的临床现状，您如何看待此次新版医保将长效G-CSF限定范围拓宽至“限既往化疗曾发生重度中性粒细胞减少的患者”？这一调整会给消化道肿瘤临床实践带来哪些改变？ 殷飞教授 河北医科大学第四医院 我认为，这次医保政策更新非常重要，核心价值在于它和当前临床共识、真实世界管理需求之间实现了更好的衔接。过去医保限定强调“前次化疗曾发生重度中性粒细胞减少”，在实际执行中会遇到一个非常现实的问题：中性粒细胞减少往往出现在化疗后7~10天，而这个时间段很多患者已经离院，在院外完成血常规监测。这样一来，即便患者确实发生过严重粒缺，临床在下一周期用药时也未必总能以最便捷、最规范的方式完成认定与衔接。现在把范围拓宽为“既往化疗曾发生重度中性粒细胞减少”，就明显更符合临床实际。这里的“既往”并不局限于前一个周期，而是指患者在整个化疗过程中，只要曾经发生过符合标准的重度中性粒细胞减少，都可以纳入后续管理考量。从指南和共识角度看，这样的更新也是顺理成章的。 《肿瘤化疗导致的中性粒细胞减少诊治专家共识（2026）》已经更加明确地提出，要坚持风险评估、预防为先、分层管理的理念。对消化道肿瘤患者来说，这种政策联动的意义很直接。一方面，它提高了长效G-CSF的可及性，让更多本应获益的患者更容易在早期就得到保护；另一方面，也让医生在执行指南推荐时少了顾虑，有助于把“预防为先”的理念真正落实到日常诊疗中。 03 《肿瘤瞭望》：在长效G-CSF新医保政策落地后的临床实践中，您认为有哪些关键细节需要特别注意？医保条件放宽后，哪些消化道肿瘤患者会明显获益？哪些方案更容易发生3–4度中性粒细胞减少，需要临床更早识别并保护？ 殷飞教授 河北医科大学第四医院 我觉得这次政策放宽后，临床最重要的不是简单理解成“能报销了”，而是要真正把它转化为更精准的风险识别和更及时的预防策略。 首先，医生需要准确把握政策中的核心判断标准，也就是重度中性粒细胞减少主要看中性粒细胞绝对计数（ANC），而不是笼统看白细胞总数。一般来说，ANC低于1.0×10^9/L即可界定为重度中性粒细胞减少。这个概念必须讲清楚，否则无论是病历记录、医患沟通还是院内执行，都容易出现偏差。 第二，医保条件放宽后，真正明显获益的，其实是那些既往在治疗过程中已经证明自己“容易掉白细胞”、但过去未必总能及时纳入预防路径的患者。对消化道肿瘤来说，重点包括几类人群： 既往某个化疗周期已经发生过3–4度中性粒细胞减少、但并不一定恰好发生在“前一个周期”的患者； 需要接受多周期强化治疗、又高度依赖剂量强度和治疗节奏的患者； 年龄偏大、营养状态差、术后恢复慢、合并感染风险高或器官功能储备不足的患者； 在中高强度方案基础上，还叠加免疫治疗、ADC或其他联合治疗的患者。 这些患者过去往往最容易出现一种情况：临床知道他风险高，但因为支付条件、识别节点或执行衔接的问题，没有办法尽早、持续地把预防真正做起来。现在医保条件放宽后，这部分患者可以更早被纳入长效G-CSF保护路径，受益是非常直接的。 第三，从方案风险角度讲，消化道肿瘤中确实有一些化疗方案更容易出现3–4度中性粒细胞减少，临床必须高度警惕。比如食管癌和胃癌中的DCF、DOS、TPF或DOC等高强度方案，结直肠癌中的FOLFOXIRI方案，胰腺癌中的FOLFIRINOX方案，都是临床需要重点关注的高风险场景。对于这类方案，如果患者既往已经发生过3–4度中性粒细胞减少，或者本身合并高龄、营养不良、既往放化疗史等风险因素，那么更应前移保护，而不是等到下一次再出问题。 再往前一步说，医保条件放宽后，消化道肿瘤患者的获益并不只是“可以用上药”这么简单。真正的获益体现在几个层面： 能减少3–4度中性粒细胞减少及FN的再次发生，降低严重感染风险； 能减少因为粒缺导致的延期、减量或中断，尽量维持既定方案的RDI； 能减少额外住院、抗感染治疗和检测带来的负担； 更重要的是，能让患者更大概率按计划完成治疗，把原本设计好的治疗目标真正落地。 所以我认为，这次医保政策放宽对消化道肿瘤患者最大的价值，是让那些既往已经证明自己“高风险”的患者，不再被动等待下一次粒缺发生，而是能更早进入规范、持续的保护路径。 04 《肿瘤瞭望》：在药物选择上，您通常会如何考量？ 殷飞教授 河北医科大学第四医院 要在药物选择上兼顾机制、疗效、安全性和可及性。当前不同代际的长效G-CSF各有技术路线。较早期的产品多采用聚乙二醇（PEG）修饰策略，临床上会关注其潜在蓄积、致敏性以及免疫原性等问题；还有产品采用Fc融合蛋白路线，或使用中国仓鼠卵巢（CHO）细胞表达体系，临床也会从免疫反应和工艺安全角度进行综合考量。 从技术迭代来看，第四代长效G-CSF之所以受到关注，在于它提供了新的长效化思路。以阿格司亭α为代表的相关产品，采用人血清白蛋白（HSA）融合技术，并基于改构分子设计和毕赤酵母发酵工艺，希望在长效化、安全性和分子活性之间取得更好的平衡。 阿格司亭α的关键III期研究数据来看，在第1化疗周期，阿格司亭α组4级中性粒细胞减少持续时间达到对照组非劣效；而在第2到第4化疗周期中，4级中性粒细胞减少的持续时间和发生率进一步下降。 在所有化疗周期中，3/4级中性粒细胞减少发生率较对照组最高可降低42.4%，第2周期FN发生率更快降至0%，第2到第4周期整体FN发生率也低于对照组，同时抗生素使用率呈现更优趋势。结合现有证据来看，这类第四代长效G-CSF在4级CIN持续时间控制、后续周期FN发生率降低等方面都显示出积极结果，也更符合我们在临床上“首战即决战”的管理理念。因为很多患者一旦在早期周期出现明显骨髓抑制，后续整个治疗节奏都会受到影响。所以在具备医保可及性的基础上，优先考虑机制更先进、循证证据更充分、疗效和安全性更均衡的产品，通常更有利于为患者提供稳定保护。 结语： 对消化道肿瘤患者而言，CIN/FN管理早已不是单纯的对症处理问题，而是贯穿全程治疗质量的重要一环。随着医保政策持续优化、共识推荐不断更新，以及更高代际长效G-CSF逐步进入临床，支持治疗也正在从“被动补救”走向“主动预防”。如何把政策、证据和临床路径更好衔接，值得在后续实践中持续推进。 殷飞 教授 河北医科大学第四医院东院消化科主任 博士生导师 中国临床肿瘤学会神经内分泌肿瘤专家委员会常委 中国抗癌协会间质瘤专业委员会委员 中国抗癌协会神经内分泌肿瘤专业委员会委员 中国抗癌协会整合肾脏病专业委员会常委 中国医促会神经内分泌肿瘤专业委员会委员 中国医促会神经内分泌肿瘤专业委员会胃肠胰神经内分泌肿瘤学组组长 中国研究型医院学会肿瘤学专业委员会常委 中国医师协会大肠癌专业委员会委员 中国医师协会胰腺病专业委员会委员 北京癌症基金会结直肠癌防治专委会副主委 河北省抗癌协会整合肿瘤学分会主委 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Agreement will help state ADAP programs provide access to IDVYNSO™ (doravirine/islatravir) for eligible individuals RAHWAY, N.J.--(BUSINESS WIRE)-- $MRK #MRK --Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced an agreement with the ADAP Crisis Task Force (ACTF) to help state AIDS Drug Assistance Programs (ADAPs) provide access to the company’s new once-daily HIV treatment, IDVYNSO™ (doravirine/islatravir). In 2024, state ADAPs supported more than 250,000 people with HIV in the United States. IDVYNSO was approved by the U.S. Food and Drug Administration (FDA) in April 2026 as a new, two-drug single-tablet regimen of 100 mg doravirine and 0.25 mg islatravir, for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. “ADAP programs play a critical role in supporting access to treatment for people living with HIV who are uninsured or underserved,” said Tim Horn, Director, Medication Access, National Alliance of State and Territorial AIDS Directors (NASTAD). “We appreciate Merck’s continued engagement and its willingness to work collaboratively to help address the critical access challenges facing state ADAP programs.” “Merck is pleased to have reached this agreement with the ADAP Crisis Task Force to expand access to IDVYNSO for eligible people with HIV,” said Conrod Kelly, U.S. HIV business unit head, Merck. “This agreement reflects our long-standing commitment to working with the ACTF, state ADAPs and the HIV community to strengthen access and help address persistent gaps in care.” For individuals with questions about coverage and affordability, the Merck Access Program may be able to provide information about insurance benefits, estimated out-of-pocket costs and co-pay assistance options for eligible patients. The Merck Access Program for IDVYNSO Merck offers support to individuals who are prescribed IDVYNSO, including information about patient insurance coverage and out-of-pocket costs, co-pay assistance for eligible, commercially insured individuals, and how individuals may access IDVYNSO through The Merck Access Program. For additional information, healthcare providers and individuals can call 1-877-709-4455 or visit . About IDVYNSO IDVYNSO is a fixed-dose combination of two medicines, doravirine and islatravir. Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase. Islatravir is a potent, next-generation nucleoside analog reverse transcriptase inhibitor (NRTI) that blocks HIV-1 replication by multiple mechanisms including: inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and induction of structural changes in the viral DNA (delayed chain termination). Selected Safety Information for IDVYNSO Contraindications IDVYNSO is contraindicated when co-administered with: drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of IDVYNSO. lamivudine (3TC) or emtricitabine (FTC) as significant decreases in islatravir-triphosphate (ISL-TP) concentrations may occur, which may decrease the effectiveness of IDVYNSO. (See Drug Interactions) Warnings and Precautions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during postmarketing experience with doravirine-containing regimens. In addition, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) was reported with IDVYNSO in a clinical trial. Discontinue IDVYNSO, and other medications associated with these reactions, immediately if a painful rash with mucosal involvement, a progressive severe rash, or a rash with constitutional symptoms, eosinophilia, lymphadenopathy, or other organ involvement develops. Close clinical monitoring, and appropriate therapy should be initiated. The concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance or possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO. Consider the potential for drug interactions prior to and during IDVYNSO therapy, review concomitant medications during IDVYNSO therapy, and monitor for adverse reactions. (See Drug Interactions) Adverse Reactions The most common adverse reactions (incidence ≥ 2%, all grades in any treatment group) reported in virologically suppressed participants in the IDVYNSO treatment groups in Trials 051 and 052, respectively, were: diarrhea (3% and 1%), dizziness (2% and 1%), fatigue (2% and 1%), abdominal distension (2% and 1%), headache (2% and 1%) and weight increased (2% and <1%). A single case of severe immune thrombocytopenia (platelet count nadir of 2 x10 9 /L) characterized by abrupt onset of subcutaneous hematoma, petechiae, and hematuria was reported in a participant 32 days after initiating IDVYNSO. The case resolved with discontinuation of IDVYNSO, in conjunction with treatments including corticosteroids and intravenous immunoglobulin (IVIG). Among all participants in Trials 052 and 051, there were no patterns of platelet decreases over time with IDVYNSO and no differences between treatment arms in mean change from baseline in platelet count. Drug Interactions IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Co-administration of IDVYNSO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce the efficacy of IDVYNSO. If IDVYNSO is co-administered with rifabutin, one tablet of doravirine should be taken approximately 12 hours after the dose of IDVYNSO. Co-administration of IDVYNSO with other moderate CYP3A inducers is not recommended. Co-administration of IDVYNSO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. Co-administration of IDVYNSO is not recommended with deoxycytidine kinase (dCK) substrates (e.g., nucleoside antimetabolites) as they may reduce the exposure of islatravir-triphosphate or with adenosine deaminase (ADA) inhibitors (e.g., pentostatin) as they may increase the exposure of islatravir. (see Contraindications) Use in Specific Populations There are insufficient human data on the use of IDVYNSO during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Healthcare providers are encouraged to call the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263 to report pregnancy outcomes in individuals exposed to IDVYNSO. It is unknown whether IDVYNSO or any of its components are present in human milk, affects human milk production, or has effects on the breastfed infant. Inform patients that the potential risks of breastfeeding include: (1) HIV-1 transmission (in infants without HIV-1), (2) developing viral resistance (in infants with HIV-1), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. Clinical trials in virologically suppressed participants who received IDVYNSO included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older. Overall differences in response have not been identified between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment of IDVYNSO is required in patients with eGFR ≥30 mL/min/1.73 m 2 . IDVYNSO is not recommended in patients with eGFR <30 mL/min/1.73 m 2 and has not been studied in participants undergoing dialysis. No dosage adjustment of IDVYNSO is recommended in patients with mild or moderate hepatic impairment (Child- Pugh Class A or B). IDVYNSO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and therefore is not recommended in these patients. IDVYNSO does not have activity against hepatitis B virus (HBV). Patients with HBV coinfection who switch to IDVYNSO from an antiretroviral regimen with activity against HBV, and patients on IDVYNSO who are newly diagnosed with HBV coinfection, should be closely monitored and specific anti-HBV therapy should be considered, as clinically appropriate. Merck’s Commitment to HIV For 40 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV. We are researching for real life and want to ensure people are not defined by HIV. Our work focuses on transformational innovations, collaborations with others in the global HIV community and access initiatives aimed at helping to end the HIV epidemic for everyone. About Islatravir (MK-8591) and Merck’s HIV Research Islatravir (MK-8591) is Merck’s potent, next-generation nucleoside analog reverse transcriptase inhibitor (NRTI) that blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and induction of structural changes in the viral DNA (delayed chain termination). Islatravir is approved in combination with Merck’s NNRTI, doravirine, in the United States and Japan as IDVYNSO™, a once-daily, single-tablet regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. Islatravir is also under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential once-weekly treatments for HIV-1, in Merck's proprietary two-drug regimens. Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1 [ISLEND-1 ( NCT06630286 ) and ISLEND-2 ( NCT06630299 )], and islatravir in combination with Merck’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development (MK-8591B-060, NCT06891066 and MK-8591B-062, NCT07266831 ) as an oral once-weekly treatment. MK-8527 is Merck’s investigational, novel, once-monthly, oral candidate for pre-exposure prophylaxis (PrEP) for HIV-1. In collaboration with the Gates Foundation, the Phase 3 EXPrESSIVE-10 trial (MK-8527-010, NCT07071623 ) trial is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among women and adolescent girls in sub-Saharan Africa. The Phase 3 EXPrESSIVE-11 trial (MK-8527-011, NCT07044297 ) in 16 countries is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among people likely to be exposed to HIV-1. Both trials are now enrolling. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( ). Please see Prescribing Information for IDVYNSO™ (doravirine and islatravir) at and Patient Information for IDVYNSO at . Contacts Media Contacts: Melissa Moody (215) 407-3536 Kristina Rey (917) 880-0025 Investor Contacts: Ayn Wisler (917) 691-6218 Peter Dannenbaum (732) 594-1579