Blood Neoplasia最新文献_第2页

Predicting secondary myeloid neoplasms in acquired aplastic anemia using machine learning models 使用机器学习模型预测获得性再生障碍性贫血的继发性髓系肿瘤

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100163

Ahmet Celal Toprak ∗ , Mutlu Mete ∗ , Julia J. Shi , Daria V. Babushok , Carmelo Gurnari , Jaroslaw P. Maciejewski , Zoe Bass , Zehra Tombul , Carlos. I. A. Santos , Munevver N. Duran , Hussein Awada , Ibrahim Ibrahim , Alper Olcal , Yusuf Ozcan , Leslie Guerrero , Julio Alvarenga Thiebaud , Taha Bat

Abstract

Patients with acquired aplastic anemia (AA) treated with immunosuppressive therapy (IST) face up to a 20% long-term risk of developing secondary myeloid neoplasms (sMNs), including acute myeloid leukemia and myelodysplastic syndromes. Although hematopoietic stem cell transplantation (HSCT) is curative and prevents sMNs, older patients and those lacking suitable donors have historically received IST as first-line therapy. Recent improvements in HSCT outcomes have expanded transplant eligibility, highlighting the need for tools to better identify patients at high risk for sMN. Validated predictive models could help guide early HSCT consideration or tailor surveillance strategies. We developed 2 binary machine learning models to predict sMN development in patients with acquired AA at clinically relevant time points: diagnosis (model 1) and 6 months after IST response (model 2). We analyzed data from 275 adult patients with AA treated at University of Texas Southwestern, Cleveland Clinic, and the Hospital of the University of Pennsylvania between 1975 and 2023. Seventy-nine clinical variables were collected, including demographics, somatic mutations, and treatment response. Neural networks were trained with leave-1-out crossvalidation. Both models achieved strong performance (area under the curve, 0.82; sensitivity, 0.82, specificity, 0.73). Shared key predictors included DNMT3A mutation, CUX1 mutation, total mutation count, and age. TET2 mutation was specific to model 1; paroxysmal nocturnal hemoglobinuria clone presence was unique to model 2. High-risk classification was significantly associated with worse overall survival (P < .0001). These findings support the feasibility of machine learning–based sMN risk prediction in AA. With training on larger data sets and external validation, these models may support individualized decision-making around HSCT and post-IST surveillance.

摘要接受免疫抑制治疗（IST）的获得性再生障碍性贫血（AA）患者面临高达20%的长期发展为继发性髓系肿瘤（sMNs）的风险，包括急性髓系白血病和骨髓增生异常综合征。虽然造血干细胞移植（HSCT）可以治愈并预防sMNs，但老年患者和缺乏合适供体的患者历来将IST作为一线治疗。最近HSCT结果的改善扩大了移植资格，强调需要更好地识别sMN高风险患者的工具。经过验证的预测模型可以帮助指导早期的HSCT考虑或定制监测策略。我们开发了2个二元机器学习模型来预测获得性AA患者在临床相关时间点的sMN发展：诊断（模型1）和IST反应后6个月（模型2）。我们分析了1975年至2023年间在德克萨斯大学西南分校、克利夫兰诊所和宾夕法尼亚大学医院接受治疗的275名AA成年患者的数据。收集了79个临床变量，包括人口统计学、体细胞突变和治疗反应。神经网络采用留1交叉验证法进行训练。两种模型均取得了较好的效果（曲线下面积0.82，灵敏度0.82，特异性0.73）。共享的关键预测因子包括DNMT3A突变、CUX1突变、总突变数和年龄。TET2突变是模型1特有的；阵发性夜间血红蛋白尿的克隆存在是模型2所特有的。高危分类与较差的总生存率显著相关（P < .0001）。这些发现支持了在AA中基于机器学习的sMN风险预测的可行性。通过对更大数据集的训练和外部验证，这些模型可以支持围绕HSCT和ist后监测的个性化决策。

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引用次数: 0

Hoff FW, Yocum AO, Borate UM, et al. Beat AML genetic risk stratification model in a cohort of older VEN/HMA-treated patients with AML. Blood Neoplasia. 2025;2(3):100125. Hoff FW, Yocum AO, Borate UM，等。在老年VEN/ hma治疗的AML患者队列中击败AML遗传风险分层模型。血液肿瘤。2025;2(3):100125。

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100169

引用次数: 0

Luspatercept treatment affects immune-regulatory subsets in patients with MDS with ring sideroblasts Luspatercept治疗影响环形铁母细胞MDS患者的免疫调节亚群

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100170

Stefania Leone , Francesco Grimaldi , Mara Memoli , Giulia Scalia , Annamaria Vincenzi , Maria Di Perna , Giuseppe Cerciello , Antonio Vassallo , Fabrizio Pane , Alessandra Picardi , Giuseppe Terrazzano , Giuseppina Ruggiero , Flavia Carriero , Valentina Rubino

引用次数: 0

T-cell immune profile changes predict durable response to nivolumab-rituximab in treatment-naïve FL t细胞免疫谱改变预测treatment-naïve FL患者对尼武单抗-利妥昔单抗的持久反应

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100168

Rachel M. Koldej , Allison Barraclough , Huw Morgan , Sze Ting Lee , Nicholas Holzwart , Minu Koshy , Charmaine Smith , Geoffrey Chong , Michael Gilbertson , Colm Keane , Denise Lee , Leonid Churilov , David S. Ritchie ∗ , Eliza A. Hawkes ∗

引用次数: 0

Real-world analysis of polycythemia vera treatment reveals nonadherence to NCCN guidelines in a large proportion of patients 真性红细胞增多症治疗的实际分析显示，很大一部分患者不遵守NCCN指南

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100167

Ghaith Abu-Zeinah , Anthony M. Hunter , Joseph J. Shatzel , Abdulraheem Yacoub , Albert Qin , Hung-Lun Chien , Ruben A. Mesa

引用次数: 0

Second malignancies among older patients with classical myeloproliferative neoplasms treated with ruxolitinib 鲁索利替尼治疗的老年经典骨髓增殖性肿瘤患者中的第二恶性肿瘤

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100159

Rong Wang ∗ , Jessica M. Stempel ∗ , Rory M. Shallis , Scott F. Huntington , Amer M. Zeidan , Natalia Neparidze , Mengyang Di , Jan Philipp Bewersdorf , Lourdes Mendez , Xiaomei Ma † , Nikolai A. Podoltsev †

Abstract

Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are classical Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) associated with an increased risk of development of second primary malignancies (SMs). The reasons for solid and lymphoid SMs are unclear, but a therapy-related effect has been invoked. Although an increased risk of nonmelanoma skin cancers is associated with the use of ruxolitinib (RUX), its influence on the development of other forms of SMs remains controversial. We conducted a retrospective cohort analysis to assess associations between RUX and SMs among older patients diagnosed with MPN from 2012 to 2019 in the Surveillance, Epidemiology, and End Results–Medicare–linked database. We identified 6043 patients (2396 with PV, 2944 with ET, 703 with MF) with a median age of 76 years (interquartile range [IQR], 71-82). After a median follow-up of 3.66 (IQR, 2.25-5.17) and 3.02 years (IQR, 1.84-4.75) for 513 RUX users and 5530 nonusers, respectively, 469 patients developed an SM: 383 solid and 86 lymphoid. In the multivariable proportional subdistribution hazard regression model with death as a competing risk, the risk of developing any SM did not differ by RUX use status (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.65-1.42; P = .84) or by proportion of days covered by RUX (every 10% increase; HR, 1.00; 95% CI, 0.96-1.05; P = .95). RUX exposure did not affect the risk of solid SM (HR, 0.77; 95% CI, 0.48-1.23; P = .27) or lymphoid SM (HR, 1.73; 95% CI, 0.79-3.80; P = .17). Our results suggest that RUX use does not increase the risk of SM in older patients with MPN.

真性红细胞增多症（PV）、原发性血小板增多症（ET）和骨髓纤维化（MF）是典型的费城染色体阴性骨髓增生性肿瘤（mpn），与发展为第二原发性恶性肿瘤（SMs）的风险增加有关。实性和淋巴样sm的原因尚不清楚，但与治疗相关的效应已被引用。虽然非黑色素瘤皮肤癌的风险增加与ruxolitinib （RUX）的使用有关，但其对其他形式的SMs发展的影响仍存在争议。我们在监测、流行病学和最终结果-医疗保险相关数据库中进行了回顾性队列分析，以评估2012年至2019年诊断为MPN的老年患者中RUX和SMs之间的关系。我们确定了6043例患者（2396例PV， 2944例ET， 703例MF），中位年龄为76岁（四分位数范围[IQR]， 71-82）。513名RUX使用者和5530名非使用者的中位随访时间分别为3.66年（IQR, 2.25-5.17）和3.02年（IQR, 1.84-4.75）， 469名患者发生SM: 383名实性SM和86名淋巴性SM。在以死亡为竞争风险的多变量比例亚分布风险回归模型中，发生任何SM的风险与RUX使用状况（风险比[HR]， 0.96； 95%置信区间[CI]， 0.65-1.42; P = 0.84）或RUX覆盖天数的比例（每增加10%；HR, 1.00; 95% CI, 0.96-1.05; P = 0.95）没有差异。暴露于RUX并不影响固体性SM（风险比，0.77;95% CI, 0.48-1.23; P = 0.27）或淋巴性SM（风险比，1.73;95% CI, 0.79-3.80; P = 0.17）的风险。我们的研究结果表明，RUX的使用不会增加老年MPN患者SM的风险。

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引用次数: 0

Application of the International Working Group MDS molecular taxonomy classes to a single institution cohort 国际工作组MDS分子分类类在单一机构队列中的应用

Blood Neoplasia

Pub Date : 2025-11-01 DOI: 10.1016/j.bneo.2025.100162

Rohiverth Guarecuco , Lisa Yuen , Maxwell Roth , Brandon J. Aubrey , Andrew M. Brunner , Robert P. Hasserjian

Abstract

Hematopathology classification increasingly relies on genetics, but most myelodysplastic syndromes/neoplasms (MDS) remain classified based on morphologic criteria such as blasts and dysplasia. Recently, the MDS International Working Group (IWG) developed an MDS molecular taxonomy using a large international cohort. Here, we applied this taxonomy to a single-institution cohort of 392 patients with MDS and oligomonocytic chronic myelomonocytic leukemia (oCMML) receiving modern standard of care. Cases were also classified per International Consensus Classification (ICC) and World Health Organization (WHO) 5th edition (WHO5). All patients were assigned to a molecular class; TP53-complex karyotype (TP53-CK; 29%), IDH-STAG2 (14%), SF3B1 (9%), and No-event (6%) were the most frequent. Clinical presentation varied across classes, with oCMML being most frequent in biallelic-TET2 (bi-TET2) (42%), EZH2-ASXL1 (50%), and clonal cytopenia of undetermined significance (CCUS)-like classes (33%). Molecular classifications were stable; only 18% changed upon follow-up. Molecular classes showed significant differences in overall survival (OS). On multivariable analyses (MVAs) that included stem cell transplant, longer OS was seen with SF3B1, del5q, and bi-TET2; shorter OS was seen with TP53-CK and −7/SETBP1. In MVAs for WHO5 and ICC entities, oCMML2 was the only morphologically defined entity that affected OS. For predicting OS, IWG molecular classification had a Harrell's C-index of 0.75, compared with WHO5 and ICC Harrell's C-indices of 0.74 and 0.73, respectively. Altogether, these results show that the IWG molecular taxonomy can be applied in routine practice, with several classes exhibiting distinct clinical features and outcomes.

病理分类越来越依赖于遗传学，但大多数骨髓增生异常综合征/肿瘤（MDS）仍然基于形态学标准分类，如母细胞和发育不良。最近，MDS国际工作组（IWG）利用大量的国际队列开发了MDS分子分类。在这里，我们将这种分类法应用于392名接受现代标准治疗的MDS和少单细胞慢性髓单细胞白血病（oCMML）患者的单机构队列。病例也按照国际共识分类（ICC）和世界卫生组织（WHO）第5版（WHO5）进行分类。所有患者被分配到一个分子类；TP53-complex核型（TP53-CK; 29%）、IDH-STAG2（14%）、SF3B1（9%）和No-event（6%）最为常见。不同类别的临床表现各不相同，oCMML最常见于双等位基因- tet2 (bi-TET2)（42%）、EZH2-ASXL1（50%）和克隆性细胞减少症（CCUS）样类别（33%）。分子分类稳定；在随访中只有18%发生了变化。分子分类显示总生存期（OS）有显著差异。在包括干细胞移植在内的多变量分析（MVAs）中，SF3B1、del5q和bi-TET2患者的生存期更长；TP53-CK和−7/SETBP1的OS较短。在WHO5和ICC实体的MVAs中，oCMML2是影响OS的唯一形态学定义的实体。在预测OS方面，IWG分子分类的Harrell’s c指数为0.75，而WHO5和ICC的Harrell’s c指数分别为0.74和0.73。总之，这些结果表明，IWG分子分类可以应用于日常实践，有几个类别表现出不同的临床特征和结果。

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引用次数: 0

Extended long-term follow-up and the survival of Stop Imatinib study 延长长期随访和停止伊马替尼的生存研究

Blood Neoplasia

Pub Date : 2025-10-27 DOI: 10.1016/j.bneo.2025.100177

François-Xavier Mahon , Stéphanie Dulucq , Delphine Réa , Franck-Emmanuel Nicolini , Françoise Rigal-Huguet , Katerina Machova Polakova , Viviane Dubruille , Marie-Pierre Noel , Jean-Christophe Ianotto , Bruno Villemagne , Émilie Cayssials , Sophie Park , Philippe Rousselot , Gabriel Etienne

Abstract

The French Stop Imatinib study (STIM1) was one of the first trials to explore the possibility of discontinuing imatinib in patients with chronic myeloid leukemia (CML) who had achieved a sustained molecular response (at least a 4.5-log reduction). The stringent criteria for molecular recurrence (MRec) were defined as BCR::ABL1 transcript positivity confirmed by a second test showing either a 1-log increase or loss of major molecular response across consecutive assessments. This comprehensive update presents long-term follow-up data from the STIM1 study, with a median molecular follow-up of 12.8 years (range, 0.8-15). Results showed a molecular recurrence-free survival rate of 37% (95% confidence interval [CI], 28-48) at 120 months, and 35% (95% CI, 26-46) at 156 months after imatinib discontinuation. Importantly, no patients experienced CML progression during the follow-up. Overall survival rates were 97% (95% CI, 94-100) at 10 years and 88% (95% CI, 81-96) at 20 years. A case of late MRec, confirmed through DNA BCR::ABL1 breakpoint analysis and comparison at diagnosis and recurrence, indicated the persistence of the original disease rather than the onset of new CML. This study offers valuable insights into the safety and feasibility of imatinib discontinuation for patients with CML, supporting long-term remission while maintaining survival. This study was registered at ClinicalTrials.gov as #NCT00478985.

法国停止伊马替尼研究（STIM1）是首批探索慢性髓性白血病（CML）患者停止伊马替尼的可能性的试验之一，这些患者已经实现了持续的分子反应（至少减少4.5 log）。严格的分子复发标准（MRec）被定义为BCR::ABL1转录阳性，通过第二次测试证实，在连续评估中显示主要分子反应增加或减少1个对数。这一全面的更新提供了STIM1研究的长期随访数据，中位分子随访时间为12.8年（范围0.8-15年）。结果显示，伊马替尼停药后120个月无分子复发生存率为37%(95%置信区间[CI]， 28-48)， 156个月无分子复发生存率为35% （95% CI, 26-46）。重要的是，随访期间没有患者出现CML进展。10年总生存率为97% (95% CI, 94-100)， 20年总生存率为88% （95% CI, 81-96）。1例晚期MRec，通过DNA BCR::ABL1断点分析和诊断与复发时的比较证实，表明原疾病持续存在，而不是新CML的发生。这项研究为CML患者停用伊马替尼的安全性和可行性提供了有价值的见解，支持长期缓解，同时维持生存。该研究已在ClinicalTrials.gov注册为#NCT00478985。

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引用次数: 0

Tisagenlecleucel in combination with ibrutinib in adults with relapsed and/or refractory large B-cell lymphomas Tisagenlecleucel联合依鲁替尼治疗成人复发和/或难治性大b细胞淋巴瘤

Blood Neoplasia

Pub Date : 2025-10-24 DOI: 10.1016/j.bneo.2025.100176

Julio C. Chavez , Ellen Napier , Attilio Bondanza , Andrew Lewandowski , Jennifer Mataraza , David Quinn , Paul Kwon , Frederick L. Locke , Boris Engels , Rakesh Awasthi , Petrina Georgala , Malgorzata Leyk , David Hynds , Michele Moschetta , Stephen J. Schuster

Abstract

The mechanisms underlying chimeric antigen receptor (CAR) T-cell failure are not fully understood; however, T-cell differentiation and presence of an immunosuppressive tumor microenvironment are thought to contribute. Ibrutinib, a Bruton tyrosine kinase inhibitor, has been shown to modify both T-cell phenotype and tumor microenvironment. Preliminary data suggest that combining ibrutinib with tisagenlecleucel may improve efficacy of CAR T-cell therapy; however, it is unknown whether the timing of ibrutinib treatment affects clinical outcomes. This phase 1b exploratory study assessed tisagenlecleucel in combination with ibrutinib for safety, efficacy, and feasibility in adult patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Ibrutinib (560 mg/d) was started ≥21 days before apheresis (preapheresis arm, n = 4) or after apheresis for ≥21 days before tisagenlecleucel infusion (postapheresis arm, n = 6). Both arms received ibrutinib continuously thereafter for up to 24 months after infusion. As of study termination (1 November 2021), 10 patients were treated and underwent posttisagenlecleucel response assessment. Final product manufactured from patients in the preapheresis arm had higher interferon gamma and interleukin-2 release and a reduction in senescent T cells. Fewer patients in the preapheresis arm vs the postapheresis arm experienced cytokine release syndrome (1/4 vs 5/6) or death (1/4 vs 4/6). Although increased tisagenlecleucel expansion was observed in the postapheresis arm, a higher response rate was observed in the preapheresis arm (4/4 vs 3/6). Altogether, these findings suggest administering ibrutinib before leukapheresis may modify T-cell characteristics in the collected material, thereby improving final CAR T-cell product quality and clinical outcomes for patients with R/R LBLC treated with tisagenlecleucel. This trial was registered at www.clinicaltrials.gov as #NCT03876028.

嵌合抗原受体（CAR） t细胞衰竭的机制尚不完全清楚；然而，t细胞分化和免疫抑制肿瘤微环境的存在被认为是原因之一。Ibrutinib是一种布鲁顿酪氨酸激酶抑制剂，已被证明可以改变t细胞表型和肿瘤微环境。初步数据表明，依鲁替尼联合tisagenlecleucel可提高CAR - t细胞治疗的疗效；然而，目前尚不清楚伊鲁替尼治疗的时机是否会影响临床结果。这项1b期探索性研究评估了tisagenlecleucel联合依鲁替尼治疗复发/难治性（R/R）大b细胞淋巴瘤（LBCL）成人患者的安全性、有效性和可行性。伊鲁替尼（560mg /d）在采前≥21天（采前组，n = 4）或采后≥21天（采后组，n = 6）开始使用。此后，两组患者在输注后连续接受伊鲁替尼治疗长达24个月。截至研究终止（2021年11月1日），10名患者接受了治疗并进行了tisagenagenle后反应评估。采前组患者生产的最终产品具有更高的干扰素γ和白细胞介素-2释放，衰老T细胞减少。与采后组相比，采前组较少患者出现细胞因子释放综合征（1/4 vs 5/6）或死亡（1/4 vs 4/6）。虽然在采后组观察到增加的组织白细胞扩张，但采前组观察到更高的反应率（4/4 vs 3/6）。总之，这些研究结果表明，在白细胞分离前给予依鲁替尼可能会改变收集材料中的t细胞特征，从而改善最终的CAR - t细胞产品质量，并改善经tisagenlecucel治疗的R/R LBLC患者的临床结果。该试验在www.clinicaltrials.gov注册为#NCT03876028。

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引用次数: 0

Dual FLT3/PIM inhibitor dapolsertib in acute myeloid leukemia: results from the phase 1/2 DIAMOND-01 trial 双FLT3/PIM抑制剂dapolsertib治疗急性髓性白血病：1/2期DIAMOND-01试验结果

Blood Neoplasia

Pub Date : 2025-10-24 DOI: 10.1016/j.bneo.2025.100178

Giovanni Martinelli , Scott R. Solomon , Sudipto Mukherjee , Armando Santoro , Stephen A. Strickland , Susana Vives , Farhad Ravandi , Roland B. Walter , Rachel J. Cook , Ewa Lech-Maranda , Maria Calbacho , Agnieszka Wierzbowska , Giovanni Marconi , Evelyn Acuña-Cruz , Isabel Cano-Ferri , Francesco Bertolini , Tomasz Rzymski , Alessandro Paoli , Giovanni Marino Merlo , Faten Koraichi Auriol , Pau Montesinos

Abstract

Acute myeloid leukemia (AML) is an aggressive hematopoietic cancer with poor survival outcomes. Despite improvements with recent FMS-like tyrosine kinase 3 (FLT3) inhibitors, resistance is common, and responses are short. Dapolsertib (MEN1703) is a novel, first-in-class dual inhibitor of PIM (proviral integration site for Moloney murine leukemia virus) and FLT3 kinases, with activity in both FLT3-mutated and wild-type cells. A phase 1/2 open-label, multicenter, dose-escalation study (DIAMOND-01) investigated the maximum tolerated dose (MTD) of single-agent dapolsertib and assessed its safety, efficacy, pharmacokinetic (PK) profile, pharmacodynamic biomarkers, and genomics in patients with AML with no standard therapeutic options available. Seventy-three patients received oral doses of dapolsertib ranging from 25 to 150 mg per day (14 consecutive days over 21-day cycles). In the dose-escalation phase, the MTD was 125 mg and was selected for dose expansion. The most common grade ≥3 adverse events in patients receiving 125 mg were pneumonia (38%), thrombocytopenia (30%), and anemia (27%); most of these events were deemed not treatment related. For patients receiving 125 mg dapolsertib (n = 55), the overall response rate was 9%, with a median 2.07-month duration of response, and 4 of 5 responses were observed in patients with isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations. PK analysis indicated rapid absorption of oral dapolsertib, an elimination half-life suitable for once daily dosing and a PK independent of formulation and IDH mutational status. Pharmacodynamic activity was confirmed in 50% of evaluable patients. Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.

摘要：急性髓性白血病（AML）是一种侵袭性造血肿瘤，生存预后差。尽管最近的fms样酪氨酸激酶3 （FLT3）抑制剂有所改善，但耐药是常见的，而且反应时间很短。Dapolsertib （MEN1703）是一种新型的、首创的PIM （Moloney小鼠白血病病毒前整合位点）和FLT3激酶双抑制剂，在FLT3突变和野生型细胞中均有活性。一项开放标签、多中心、剂量递增的1/2期研究（diamd -01）调查了单药dapolsertib的最大耐受剂量（MTD），并评估了其在无标准治疗方案的AML患者中的安全性、有效性、药代动力学（PK）谱、药效学生物标志物和基因组学。73名患者接受口服dapolsertib剂量，范围为每天25至150mg（连续14天，21天周期）。在剂量递增阶段，MTD为125 mg，选择进行剂量扩展。在接受125 mg的患者中，最常见的≥3级不良事件是肺炎（38%）、血小板减少症（30%）和贫血（27%）；大多数这些事件被认为与治疗无关。对于接受125 mg dapolsertib治疗的患者（n = 55），总缓解率为9%，中位缓解持续时间为2.07个月，在异柠檬酸脱氢酶1 (IDH1)/IDH2突变患者中观察到5例缓解中有4例。PK分析表明口服dapolsertib吸收迅速，消除半衰期适合每日一次给药，PK与制剂和IDH突变状态无关。50%可评估患者的药效学活性得到证实。总体而言，dapolsertib在AML患者中显示出适度的单药活性。该试验在www.clinicaltrials.gov上注册为#NCT03008187。

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引用次数: 0