[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-458152-105":59,"doc-detail-458152-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","optimizing-lower-intensity-triplet-therapy-in-acute-myeloid-leukemia-a-practical-guide","Optimizing lower intensity triplet therapy in acute myeloid leukemia: a practical guide","","Venetoclax-based doublets with azacitidine or low-dose cytarabine represent standard care for older adults with acute myeloid leukemia (AML) or those unfit for intensive chemotherapy, yet responses are often not durable and relapse is common. Frontline triplet therapy that adds targeted agents (FLT3, IDH, or menin inhibitors) is an emerging approach under investigation. This review summarizes evidence for triplets and provides practical guidance on prescribing, emphasizing dosing schedule adjustments across induction and continuation cycles, adverse effects, and interaction considerations to support tolerability and quality of life.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/optimizing-lower-intensity-triplet-therapy-in-acute-myeloid-leukemia-a-practical-guide/458152/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/optimizing-lower-intensity-triplet-therapy-in-acute-myeloid-leukemia-a-practical-guide/458152.png","ImageObject",300,407,{"name":92,"@type":93},"Rowan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are venetoclax-based doublets considered standard care in older or unfit AML patients?","Question",{"text":113,"@type":114},"Venetoclax-based combinations with azacitidine or low-dose cytarabine are standard because they improve outcomes compared with historical non-intensive options. They also provide improved tolerability relative to intensive chemotherapy.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What factors contribute to resistance and relapse after venetoclax therapy?",{"text":118,"@type":114},"Resistance can involve changes at multiple steps in the BCL2/BH3 signaling pathway, including activation of RAS/MAPK signaling, altered expression of apoptotic proteins, reduced apoptotic effector activity, and mitochondrial alterations that limit cytochrome c release.",{"name":120,"@type":111,"acceptedAnswer":121},"What practical adjustments does the review emphasize for using triplet therapy?",{"text":122,"@type":114},"The review focuses on agent selection and modifications to minimize myelosuppression while preserving efficacy, particularly by adjusting dose schedules and therapy duration across induction and continuation cycles and considering emerging interaction-related safety data.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},458152,1791073523,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj)  \nCURRENT TREATMENT ALGORITHM OPEN   \nOptimizing lower intensity triplet therapy in acute myeloid leukemia: a practical guide  \nWei-Ying Jen 1,7, Curtis A. Lachowiez2,7, Jennifer Marvin-Peek 1, Jessica K. Altman3, Musa Yilmaz 1, Jacqueline S. Garcia 4  \n,  \nYasmin Abaza 3, Nicholas J. Short 1, Joshua F. Zeidner 5, Naval G. Daver 1, Andrew H. Wei6, Ghayas C. Issa 1 and Courtney D. DiNardo 1 ✉  \n© The Author(s) 2025  \n\n|  | Venetoclax-based doublets with azacitidine or low dose cytarabine are the standard of care for the treatment of acute myeloid leukemia (AML) in older patients or those unfit for intensive chemotherapy. However, some patients do not attain complete remission, and over time, most patients relapse. Frontline triplet therapy incorporating a targeted therapy (FLT3, IDH or menin inhibitor) is an emerging treatment concept under investigation for this population. Initial triplet regimens have yielded encouraging composite complete remission and measurable residual disease negativity rates, enabling the transition to allogeneic stem cell transplantation for eligible patients. While effective, triplets are associated with myelosuppression and cytopenia-related toxicities, which can affect treatment tolerability and quality of life. In this review, we summarize the available evidence for triplet therapy in AML and offer our recommendations on the practical application of triplets in clinical practice, with particular focus on adjustments to dosing schedules in induction and continuation cycles. We also outline drug-specific adverse effects and |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| interactions based on emerging clinical data to help guide the clinician, given the increasing use of novel combination therapies. |  |  |\n|  | Blood Cancer Journal (2026)16:6; [https://doi.org/10.1038/s41408-025-01429-z](https://doi.org/10.1038/s41408-025-01429-z) |  |\n|  |  |  |\n\nINTRODUCTION  \nAcute myeloid leukemia (AML) is a hematological malignancy characterized by clonal diversity and evolution [1–3] . Prior to the approval of venetoclax (VEN), the treatment options for patientsunfit for intensive chemotherapy (IC) included monotherapy with hypomethylating agents (HMA, azacitidine [AZA] or decitabine [DAC]), or low-dose cytarabine (LDAC) [4] . The incorporation of VEN into frontline regimens with AZA or LDAC has revolutionized the treatment of older adults with AML, increasing composite complete remission (CRc) rates to two-thirds of patients and median overall survival (OS) to 14.7 months [5, 6] . However, longer follow-up has also established that responses with VEN doublets are generally not durable, with a 2-year OS of 20–40%[7, 8] . Realworld studies have subsequently reported less impressive outcomes, with median OS ranging from only 9 to 12 months [9] . Despite improved tolerability compared to standard IC regimens, protracted myelosuppression and cytopenia-related infections are common with VEN combinations. Increased cycle length (often 5–6 weeks) with reduced VEN durations (typically 7–21 days per cycle) along with growth factor support are now frequently recommended in continuation cycles to improve tolerability of VEN doublets [9, 10] .  \nRelapse and resistance to VEN therapy are multifactorial. VEN is a BH3 mimetic which binds to the anti-apoptotic protein BCL2,  \ndisrupting the interaction between BCL2 and BH3-only proteins such as BIM, leaving them free to bind apoptotic effectors BAX and BAK. Oligomerization of BAX/BAK effectors permeates the outer mitochondrial membrane, resulting in cytochrome c release and activation of caspase-dependent cell death [11, 12] . Mechanisms of resistance to VEN may target any step in this pathway, including: (i) activation of RAS/MAPK pathway and enhanced expression of pro-apoptotic proteins (e.g., BCL2, B","cbCainsU6hzNee3C","https://ap.wps.com/l/cbCainsU6hzNee3C","pdf",1439521,"English","# Introduction\n## Venetoclax-based standards and limitations\n## Rationale for triplet regimens\n## Purpose and scope of the review","[{\"question\":\"Why are venetoclax-based doublets considered standard care in older or unfit AML patients?\",\"answer\":\"Venetoclax-based combinations with azacitidine or low-dose cytarabine are standard because they improve outcomes compared with historical non-intensive options. They also provide improved tolerability relative to intensive chemotherapy.\"},{\"question\":\"What factors contribute to resistance and relapse after venetoclax therapy?\",\"answer\":\"Resistance can involve changes at multiple steps in the BCL2/BH3 signaling pathway, including activation of RAS/MAPK signaling, altered expression of apoptotic proteins, reduced apoptotic effector activity, and mitochondrial alterations that limit cytochrome c release.\"},{\"question\":\"What practical adjustments does the review emphasize for using triplet therapy?\",\"answer\":\"The review focuses on agent selection and modifications to minimize myelosuppression while preserving efficacy, particularly by adjusting dose schedules and therapy duration across induction and continuation cycles and considering emerging interaction-related safety data.\"}]","Optimizing lower intensity triplet therapy in acute myeloid leukemia: a practical guide | PDF",1790751824,28]