1. 概述

血液肿瘤是指来源于造血细胞的恶性疾病，可累及骨髓、血液及全身各个脏器和组织。临床常见的血液肿瘤主要包括各种类型的白血病、多发性骨髓瘤、淋巴瘤、骨髓增生异常综合征、骨髓增殖性肿瘤等，其发病率和死亡率均居前列，是严重危害人类健康的重大疾病。近年来，血液肿瘤在精准诊断、预后分层、免疫治疗和靶向治疗等方面取得了长足进展，尤其是嵌合抗原受体T细胞免疫疗法，在国内飞速发展，展现出了令人鼓舞的疗效和安全性，有助于改善患者的生存并提高生活质量。本文针对2024年度血液肿瘤领域中优秀的临床与基础研究进行概述，对学科十大前沿进展进行了总结，并展望了血液肿瘤的未来学科发展方向。

2024年中国血液学科

十大前沿进展

（1）CD7 CAR-T序贯异基因造血干细胞移植一体化体系^[12]

浙江大学医学院附属第一医院/良渚实验室黄河/胡永仙/王东睿/张鸿声等团队首次提出CD7 CAR-T与异基因造血干细胞移植序贯治疗的一体化策略。该策略针对复发或难治性CD7阳性白血病或淋巴瘤患者，利用患者接受供者来源的CD7 CAR-T细胞治疗后的状态，不进行清髓性预处理化疗，直接回输同一供者异基因造血干细胞，且无需免疫抑制剂预防移植物抗宿主病。该方案具有受性良好及毒副反应低的优势，尤其对无法耐受常规预处理方案的患者及老年患者。此方案被国际专家誉为“一石四鸟”的“杭州方案”：CAR-T细胞清除肿瘤细胞；免清髓化疗；无需免疫抑制剂预防移植物抗宿主病；CAR-T长期存续与移植物抗白血病作用共同预防复发。

（2）微小残留病与遗传特征结合的急性髓系白血病动态预后系统^[13]

急性髓系白血病（AML）是一种异质性的造血系统恶性肿瘤，预后因细胞遗传学和分子遗传学特征而异。早期进行预后分层对临床治疗至关重要，而现有的基于治疗前遗传异常的风险分层无法精准预测特定风险组内患者预后。中国医学科学院血液病医院王建祥/魏辉教授团队开展的研究将微小残留病（MRD）与遗传风险分类相结合，并评估其在不同风险队列中对移植决策的影响。研究结果表明，在不同ELN风险组，早期清除MRD预后价值显著，尤其对低危和中危组患者。两个强化化疗疗程后MRD阳性，复发率高、总生存率差，需进行异基因造血干细胞移植。该动态预后系统为AML患者缓解后治疗策略的选择提供了关键依据，同时也为构建基于MRD水平的综合动态预后系统提供了重要依据。

（3）首个异体CD5 CAR-T治疗T系白血病的临床研究成果^[78]

本研究评估CD5 CAR-T细胞疗法治疗R/R T-ALL的一期临床试验。共纳入19例患者，其中多数患者此前接受过CD7 CAR-T治疗但失败。患者被分为两组：A组（11例）使用既往移植供者来源的CAR-T细胞，B组（5例）使用新配型供者来源的CAR-T细胞。主要终点是评估21天内剂量限制性毒性和30天内不良事件。次要终点包括治疗反应、药代动力学和30天后的严重不良事件。16例患者接受了输注，其中10例患者接受目标剂量1×10⁶/kg。所有患者在30天内都出现了3～4级血细胞减少，1例3级感染。到30天时，所有患者（100%）都达到CR或血细胞计数不完全恢复的完全缓解。在中位随访14.3个月时，4例患者接受了移植，3例处于缓解状态，1例死于感染。12例未移植患者中，2例维持缓解，3例复发，5例死于感染，2例死于血栓性微血管病。CAR-T细胞持续存在并清除了CD5+T细胞。该研究首次报道了供者来源的敲除CD5基因的CD5 CAR-T治疗R/R T-ALL的安全性及有效性，为R/R T-ALL患者提供了治疗的新希望。

（4）阿思尼布用于CML患者，全线治疗获益^[79]

ASC4FIRST研究是一项对比口服阿思尼布与研究者所选的标准治疗TKIs（IS-TKIs：伊马替尼、尼洛替尼、达沙替尼或博舒替尼）的III期、头对头、全球多中心随机开放研究，中国共同参与且中国医学科学院血液病医院王建祥教授团队全球site中贡献第一。该研究达到双48周主要终点，结果均具有显著临床统计学差异，完整研究数据已发表在《新英格兰医学杂志》。48周MMR率阿思尼布对比IS-TKIs提升约19%（67.7% vs. 49.0% P＜0.001）；较伊马替尼提升约30%（69.3% vs.49.0% ，P＜0.001）。同时阿思尼布相关不良事件(AE)、导致治疗中断和停止的患者比例更低，安全性和耐受性更优。基于该研究结果，FDA获批其用于新诊断CML-CP期成人患者，同时NCCN 2025最新版指南将阿思尼布推荐为新诊断CML-CP期患者的治疗药物；CACA最新指南-CML部分也指出阿思尼布可作为新诊断CML-CP期的潜在治疗选择。

（5）CML的TKI治疗失败预测模型^[19]

早期识别和预测一线TKI治疗失败的高危患者，并进行干预和强化管理，对进一步提高患者生存结局具有重要意义。北京大学血液病研究所江倩教授与黄晓军院士团队基于1955例接受一线TKI（伊马替尼或二代TKI）治疗的CML-CP患者数据，开发了CML一线TKI治疗失败的临床预测模型，并通过76家中心的3454例患者数据进行了外部验证。该模型能够精准预测伊马替尼和二代TKI治疗患者的累计治疗失败率，适用于各年龄层患者。其在时间依赖性ROC曲线下的面积著优于Sokal和ELTS评分系统，并可进一步细化Sokal和ELTS各危险度人群的TKI治疗失败风险。此外，该模型还能预测分子学反应（MMR、MR4和MR4.5）的累积获得率、无疾病转化生存及CML相关生存率。倾向评分匹配（PSM）分析显示，模型识别出的中、高危患者接受二代TKI治疗的失败率显著低于伊马替尼。该研究成果近期发表于《Blood》，为CML-CP患者的个体化治疗和预后评估提供了重要工具。

（6）ZAP-70通过BCR/CCR7双通路协同促进IGHV无突变型CLL进展的机制与治疗启示^[22]

ZAP-70是一种T细胞受体信号通路激酶，在CLL B细胞中异常表达，与IGHV无突变状态及不良预后密切相关，但ZAP-70阳性患者预后不良的分子机制尚未完全阐明。华西陈镜宇教授团队近期研究成果揭示了ZAP-70在IGHV无突变的CLL患者中通过双重机制驱动CLL进展：一方面IGHV无突变的CLL中，ZAP-70增强自主性BCR信号，激活AKT/GSK-3β轴并抑制凋亡蛋白MCL1降解，从而促进细胞存活；同时，ZAP-70可增强CCR7信号通路，促进细胞骨架蛋白LCP1的丝氨酸5位点磷酸化和激活，调控肌动蛋白重塑，进而提高细胞迁移能力，并直接增强CCR7下游的PI3K/AKT信号通路，而敲低ZAP-70可显著抑制UM-CLL的迁移及生存。该研究阐明了ZAP - 70在CLL中的关键作用及具体机制，明确其对自主性BCR信号和CCR7信号的增强作用，为理解CLL的发病机制提供了新的视角，并为疾病精准分层及靶向治疗提供理论依据，对ZAP-70阳性患者的临床管理具有重要指导意义。

(7) 泽布替尼对比伊布替尼治疗中国复发/难治性CLL/SLL的疗效与安全性：ALPINE III期全球试验中国亚组分析^[63]

ALPINE是一项全球III期临床试验，旨在比较布鲁顿酪氨酸激酶抑制剂泽布替尼（zanubrutinib）与伊布替尼（ibrutinib）治疗复发/难治性（R/R）CLL/SLL的疗效和安全性。周可树教授团队报告了中国患者亚组的结果，国内入组患者共90例（泽布替尼组47例，伊布替尼组43例）。两组间基线特征平衡，除泽布替尼组男性患者比例低于伊布替尼组（55.3% vs. 69.8%）。中国亚组中11%的患者存在del(17p)，32%携带TP53突变。中位随访25.3个月时，泽布替尼组的ORR为80.9%，高于伊布替尼组的72.1%。泽布替尼组PFS显著优于伊布替尼组（HR=0.34 [95% CI, 0.15, 0.77]），OS的HR为0.45（95% CI, 0.14, 1.50）。安全性方面，泽布替尼组的≥3级治疗相关不良事件（TEAEs；64.4% vs. 72.1%）、导致停药的不良事件（6.4% vs. 14.0%）及严重TEAEs（35.6% vs. 51.2%）发生率均低于伊布替尼组。该研究首次证实，在中国R/R CLL/SLL患者中，泽布替尼较伊布替尼具有更优的疗效与安全性，尤其对高危亚组（如del(17p)/TP53突变患者）意义重大，且结果与全球数据一致，为临床选择高效低毒的BTKi提供了重要依据，推动个体化治疗策略的优化。

（8）伊基奥仑赛注射液治疗复发/难治性多发性骨髓瘤的Ⅰb/Ⅱ期临床研究^[41]

为评估伊基奥仑赛注射液是否能使RRMM患者受益，并确定输注后的总缓解率、安全性等信息，邱录贵牵头一项多中心、非随机Ⅰb/Ⅱ期FUMANBA-1研究，该研究是全人源BCMA CAR-T治疗RRMM的首个也是最大规模Ⅰb/Ⅱ期研究。纳入国内14家中心既往≥3线治疗的重度经治的103例RRMM患者，包括Ⅰb期17例和2期86例，34例（38.6%）存在高危细胞遗传学异常，既往中位治疗4线。中位随访13.8个月，总缓解率（ORR）为96.0%(97/101)，其中74.3%（75/103）达到≥完全缓解（CR）。在12例曾接受过CAR-T细胞治疗的患者中，75%（9/12）获得缓解。中位总生存期和无进展生存期（PFS）未达到，12个月PFS率为78.8%，12个月总生存率为92.2%。不良事件特征良好：103例患者中96例（93.2%）出现细胞因子释放综合征（95例[92.3%]为1~2级，1例为4级），2例（1.9%）出现免疫效应细胞相关神经毒性综合征（1~2级）。该研究是CAR-T细胞疗法注册试验中最大的亚洲人群数据，证实伊基奥仑赛注射液有助于满足RRMM人群的未满足医疗需求。

（9）首次探究MM治疗后骨髓正常浆细胞/免疫重建的临床价值^[80]

由安刚/邱录贵团队开展的该项研究共纳入了来自中国医学科学院血液病医院（中国医学科学院血液学研究所）前瞻纵向血液病队列-多发性骨髓瘤（NICHE-MM）子队列中的1363例MM患者和近5000份序贯骨髓流式数据，首次探究骨髓残存正常浆细胞（NPC）在MM不同疾病阶段的临床价值。研究结果显示，初诊或复发时骨髓中较高的正常浆细胞比例（≥5%），常与相对惰性的临床特征相关，并提示良好预后；在MRD阴性节点，骨髓中较高的正常浆细胞比例（≥0.22%）常反映免疫重建并提示更优的临床结局；而在MRD阳性节点，相较于残留肿瘤浆细胞水平，根据NPC占比（<50%、50-90%、≥90%）评估缓解深度更为精准有效。同时，基于NPC占比变化所构建的动态MRD分层体系，可实现更加精准的预后分层并指导治疗。综上，该研究证实了骨髓残存正常浆细胞不仅是MM危险分层的重要生物标志物，同样可在骨髓瘤MRD再分层和动态评估中发挥重要作用。

（10）Cilta-cel具有治愈多发性骨髓瘤的潜能^[81]

Cilta-cel已在全球多个国家被批准用于治疗复发和难治性多发性骨髓瘤，上海交通大学医学院附属瑞金医院陈赛娟院士团队开展的LEGEND-2研究是Cilta-cel的首个人体试验，该研究的5年随访报告了Cilta-cel细胞治疗后复发或难治性多发性骨髓瘤患者的长期缓解和生存结果。74名参与者入组，平均随访65.4个月，5年无进展生存率(PFS)和总生存率(OS)分别为21.0%和49.1%，随着时间的推移，生存曲线逐渐趋于平缓。完全缓解(CR)患者的PFS和OS较长，5年生存率分别为28.4%和65.7%。12例患者(16.2%)没有复发，与基线高危细胞遗传学异常无关，所有患者均恢复了正常的体液免疫。16.2%的研究人群在>5年后仍无复发，MM患者预后改善方面的这一进展有可能重塑抗骨髓瘤治疗领域，并提高部分患者治愈的可能性。

【主编】

王建祥中国医学科学院血液病医院

李建勇南京医科大学第一附属医院、江苏省人民医院

邱录贵中国医学科学院血液病医院

纪春岩山东大学齐鲁医院

【副主编】

魏辉中国医学科学院血液病医院

王迎中国医学科学院血液病医院

徐卫南京医科大学第一附属医院、江苏省人民医院

朱华渊南京医科大学第一附属医院、江苏省人民医院

安刚中国医学科学院血液病医院

易树华中国医学科学院血液病医院

叶静静山东大学齐鲁医院

章静茹山东大学齐鲁医院

【编委】（按姓氏拼音排序）

纪敏山东大学齐鲁医院

李艳中国医学科学院血液病医院

卢菲山东大学齐鲁医院

缪祎南京医科大学第一附属医院、江苏省人民医院

邱少伟中国医学科学院血液病医院

王婷玉中国医学科学院血液病医院

夏奕南京医科大学第一附属医院、江苏省人民医院

徐燕中国医学科学院血液病医院

★

参考文献（向上滑动阅览）

[1]SUN J, ZHANG S, DU R, et al. The TFG-ROS1 Fusion Is an Oncogenic Driver of Human Myeloid Leukemia [J]. Blood, 2024, 144(Supplement 1): 38-.

[2]WU Y, YUAN X, LAI X, et al. The Mutated of KRASgene Determine the Fate of KMT2A-Rearranged AML Patients [J]. Blood, 2024, 144(Supplement 1): 843-.

[3]LIU X, LIU Y, RAO Q, et al. Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells [J]. Cancer Res, 2024, 84(24): 4233-45.

[4]LIU T, WANG T, QI L, et al. CPSF6-RARgamma interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia [J]. Nat Commun, 2025, 16(1): 616.

[5]HAN G, CUI M, LU P, et al. Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance [J]. Cell Stem Cell, 2024, 31(12): 1777-93 e9.

[6]WANG H, MAO L, YANG M, et al. Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial [J]. Lancet Haematol, 2022, 9(6): e415-e24.

[7]LU J, XUE S, WANG Y, et al. Comparing the Efficacy and Safety of Venetoclax Combined with Decitabine Versus Conventional Chemotherapy As Induction Therapy for Young Adults with Newly Diagnosed Acute Myeloid Leukemia - Interim Analysis of a Multicenter, Randomized, Phase 2b Trial [J]. Blood, 2023, 142(Supplement 1): 970-.

[8]DOU X, CHEN S, WU D. Prospective Study of Avapritinib in Patients with Relapsed/Refractory or MRD-Positive Core-Binding Factor Acute Myeloid Leukemia with KIT Mutations [J]. Blood, 2024, 144: 222.

[9]WANG J, JIANG B, LI J, et al. Phase 3 study of gilteritinib versus salvage chemotherapy in predominantly Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukemia [J]. Leukemia, 2024, 38(11): 2410-8.

[10]DONG X, GUO Y, ZHANG J, et al. Potent in Vitro and In Vivo Efficacy of Hdz-C123A, a GSPT1 Degrader-Antibody Conjugate Targeting CD123 in Acute Myeloid Leukemia [J]. Blood, 2024, 144: 156.

[11]ZHANG R, ZHAO Y, CHAI X, et al. Modified CD15/CD16-CLL1 inhibitory CAR-T cells for mitigating granulocytopenia toxicities in the treatment of acute myeloid leukemia [J]. Transl Oncol, 2025, 52: 102225.

[12]HU Y, ZHANG M, YANG T, et al. Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis [J]. N Engl J Med, 2024, 390(16): 1467-80.

[13]ZHANG C, GU R, WANG H, et al. Risk stratification in the clinical application of minimal residual disease assessment in acute myeloid leukemia [J]. Cancer, 2025, 131(1): e35641.

[14]WANG Q Y, HAN Y F, LI Y H, et al. A novel prognostic scoring system for AML patients undergoing allogeneic hematopoietic stem cell transplantation with real world validation [J]. J Adv Res, 2024.

[15]JIANG Q, WEIMING L, ZHANG Y, et al. Safety and Efficacy of Tgrx-678, a Potent BCR::ABL1 allosteric Inhibitor, in Patients with Tyrosine Kinase Inhibitor Resistant and/or Intolerant Chronic Myeloid Leukemia: Updated Results of Phase 1 Study Tgrx-678 -1001 [J]. Blood, 2024, 144: 477.

[16]SAKAGUCHI H, UMEDA K, KATO I, et al. Safety and efficacy of post-haematopoietic cell transplantation maintenance therapy with blinatumomab for relapsed/refractory CD19-positive B-cell acute lymphoblastic leukaemia: protocol for a phase I-II, multicentre, non-blinded, non-controlled trial (JPLSG SCT-ALL-BLIN21) [J]. BMJ Open, 2023, 13(4): e070051.

[17]HOGAN L E, BROWN P A, JI L, et al. Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse [J]. J Clin Oncol, 2023, 41(25): 4118-29.

[18]JABBOUR E, OEHLER V G, KOLLER P B, et al. Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib: A Phase 1b Randomized Clinical Trial [J]. JAMA Oncol, 2025, 11(1): 28-35.

[19]ZHANG X, LIU B, HUANG J, et al. A predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy [J]. Blood, 2024, 144(18): 1951-61.

[20]CHENG F, WANG Y, DU X, et al. Predictive Models for Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia [J]. Blood, 2024, 144(Supplement 1): 4540-.

[21]LIU P, WANG K, LI J, et al. Global miRNA profiling reveals key molecules that contribute to different chronic lymphocytic leukemia incidences in Asian and Western populations [J]. Haematologica, 2024, 109(2): 479-92.

[22]CHEN J, SATHIASEELAN V, REDDY CHILAMAKURI C S, et al. ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia [J]. Blood Adv, 2024, 8(5): 1167-78.

[23]LU L, HU X, HAN Y, et al. ENPP2 promotes progression and lipid accumulation via AMPK/SREBP1/FAS pathway in chronic lymphocytic leukemia [J]. Cell Mol Biol Lett, 2024, 29(1): 159.

[24]PAN B, XU Z, DU K, et al. Investigation of fatty acid metabolism in chronic lymphocytic leukemia to guide clinical outcome and therapy [J]. Ann Hematol, 2024, 103(4): 1241-54.

[25]CUI Y, SHAO X, YANG H, et al. MDM2 inhibitor APG-115 synergizes with ABT-199 to induce cell apoptosis in chronic lymphocytic leukemia [J]. Front Pharmacol, 2024, 15: 1441383.

[26]LU X, SHA Y, SONG X, et al. Exploration of the Specific Mechanism of EGR2 Hotspot Mutation Mediating the Upregulation of Galectin-1 Expression in the Progression of CLL Following Treatment with BTK Inhibitor [J]. Blood, 2024, 144: 4612.

[27]SHANG C Y, BEI L Y, WU J Z, et al. NOTCH pathway mutation contributes to inferior prognosis in HBV-infected chronic lymphocytic leukemia [J]. Ann Hematol, 2024, 103(3): 833-41.

[28]CHEN X, CHEN X, ZHAO S, et al. Performance of a novel eight-color flow cytometry panel for measurable residual disease assessment of chronic lymphocytic leukemia [J]. Cytometry B Clin Cytom, 2024, 106(3): 181-91.

[29]ZHU H, MIAO Y, QIN S, et al. Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (OFCG) for First-Line Treatment of Chronic Lymphocytic Leukemia: A Multicenter, Investigator-Initiated Study (cwCLL-001 Study) [J]. Blood, 2024, 144: 3244.

[30]QIN S, JIANG R, DAI L, et al. Venetoclax plus dose-adjusted R-EPOCH (VR-DA-EPOCH) or G-EPOCH bridging to subsequent cellular therapy for the patients with transformed lymphoma a single center clinical experience [J]. Ann Hematol, 2024, 103(5): 1635-42.

[31]中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)恶性血液病诊疗指南 [M]. 人民卫生出版社.

[32]中国医师协会血液科医师分会, 中华医学会血液学分会. 中国多发性骨髓瘤诊治指南（2024年修订） [J]. 中华内科杂志, 2024, 63(12): 1186-95.

[33]中国抗癌协会血液肿瘤专业委员会骨髓瘤与浆细胞疾病学组, 中国临床肿瘤学会多发性骨髓瘤专家委员会. 高危多发性骨髓瘤诊断与治疗中国专家共识（2024年版） [J]. 中华血液学杂志, 2024, 45(5): 430-5.

[34]中国临床肿瘤学会（CSCO）骨髓瘤专家委员会, 中国抗癌协会（CACA）血液肿瘤专业委员会骨髓瘤与浆细胞疾病学组. 多发性骨髓瘤疗效评估与微小残留病监测中国指南（2024年版） [J]. 中华血液学杂志, 2024, 45(12): 1065-70.

[35]中华医学会血液学分会浆细胞疾病学组, 中国医师协会多发性骨髓瘤专业委员会. 中国髓外浆细胞瘤诊断与治疗专家共识（2024年版） [J]. 中华血液学杂志, 2024, 45(1): 8-17.

[36]中国临床肿瘤学会（CSCO）多发性骨髓瘤专家委员会. 卡非佐米治疗多发性骨髓瘤临床应用指导原则（2024年版） [J]. 白血病·淋巴瘤, 2024, 33(10): 577-86.

[37]CUI J, LIU Y, LV R, et al. Fluorescence in situ hybridization reveals the evolutionary biology of minor clone of gain/amp(1q) in multiple myeloma [J]. Leukemia, 2024, 38(6): 1299-306.

[38]CUI J, LI X, DENG S, et al. Identification of Therapy-Induced Clonal Evolution and Resistance Pathways in Minimal Residual Clones in Multiple Myeloma through Single-Cell Sequencing [J]. Clin Cancer Res, 2024, 30(17): 3919-36.

[39]MAO X, YAN W, MERY D, et al. Development and validation of an individualized and weighted Myeloma Prognostic Score System (MPSS) in patients with newly diagnosed multiple myeloma [J]. Am J Hematol, 2024, 99(4): 523-33.

[40]YAO Y, DENG S, NG J F, et al. Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth [J]. Haematologica, 2025, 110(1): 153-62.

[41]LI C, ZHOU K, HU Y, et al. Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma: The FUMANBA-1 Nonrandomized Clinical Trial [J]. JAMA Oncol, 2024, 10(12): 1681-8.

[42]QIANG W, LU J, JIA Y, et al. B-Cell Maturation Antigen/CD19 Dual-Targeting Immunotherapy in Newly Diagnosed Multiple Myeloma [J]. JAMA Oncol, 2024, 10(9): 1259-63.

[43]ZHOU D, SUN Q, XIA J, et al. Anti-BCMA/GPRC5D bispecific CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, single-centre, phase 1 trial [J]. Lancet Haematol, 2024, 11(10): e751-e60.

[44]SEARLE E, RECHER C, ABDUL-HAY M, et al. Bleximenib Dose Optimization and Determination of RP2D from a Phase 1 Study in Relapsed/Refractory Acute Leukemia Patients with KMT2A and NPM1 Alterations [J]. Blood, 2024, 144: 212.

[45]ZEIDNER J F, YUDA J, WATTS J M, et al. Phase 1 Results: First-in-Human Phase 1/2 Study of the Menin-MLL Inhibitor Enzomenib (DSP-5336) in Patients with Relapsed or Refractory Acute Leukemia [J]. Blood, 2024, 144(Supplement 1): 213-.

[46]RECHER C, O'NIONS J, ALDOSS I, et al. Phase 1b Study of Menin-KMT2A Inhibitor Bleximenib in Combination with Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with KMT2Ar or NPM1 Alterations [J]. Blood, 2024, 144(Supplement 1): 215-.

[47]ZEIDAN A M, WANG E S, ISSA G C, et al. Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007 [J]. Blood, 2024, 144(Supplement 1): 214-.

[48]ISSA G C, CUGLIEVAN B, DAVER N, et al. Phase I/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R/R AML [J]. Blood, 2024, 144(Supplement 1): 216-.

[49]BOURGEOIS W, CUTLER J, RICE H E, et al. Discerning the Landscape of Menin Inhibitor Resistance [J]. Blood, 2024, 144(Supplement 1): 724-.

[50]FREIRE P R, REGALADO B, ENER E, et al. Identification of a Novel Chromatin Structure Associated with the Transcriptional Response to Menin Inhibitors in AML [J]. Blood, 2024, 144: 952.

[51]FUJINO T, LEWIS J, CHEN B-Y, et al. Development of CAR T Cells Targeting U5 snRNP200 for the Treatment of Acute Myeloid and B-Lymphoid Leukemias [J]. Blood, 2024, 144: 371.

[52]JANG J, STANOJEVIC M, PICCINELLI S, et al. Mesothelin Targeting IL12-Engineered CAR Memory-like NK Cells Demonstrate Promising Efficacy in Acute Myeloid Leukemia [J]. Blood, 2024, 144: 917.

[53]LIU F, TARANNUM M, ZHAO Y, et al. One-Step Construction of Allogeneic CAR-NK Cells Preventing Rejection and Mediating Enhanced Anti-Tumor Responses [J]. Blood, 2024, 144: 915.

[54]LEEDOM T, MUZ B, MAGEE K, et al. W-NK1 Choreographs Innate and Adaptive Immune Responses to Provide a Robust and Durable Anti-AML Response [J]. Blood, 2024, 144: 916.

[55]TILLSON H, DRULEY T, NOUSHEEN L, et al. 3103 – A NOVEL SINGLE-CELL MEASURABLE RESIDUAL DISEASE (SCMRD) ASSAY FOR SIMULTANEOUS DNA MUTATION AND SURFACE IMMUNOPHENOTYPE PROFILING [J]. Experimental Hematology, 2024, 137: 104425.

[56]REA D, MAURO M J, BOQUIMPANI C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs [J]. Blood, 2021, 138(21): 2031-41.

[57]TESILEANU C M S, MICHALEAS S, GONZALO RUIZ R, et al. The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors [J]. Oncologist, 2023, 28(7): 628-32.

[58]HOCHHAUS A, REA D, BOQUIMPANI C, et al. Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL [J]. Leukemia, 2023, 37(3): 617-26.

[59]MAURO M J, HUGHES T P, KIM D W, et al. Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results [J]. Leukemia, 2023, 37(5): 1048-59.

[60]CORTES J E, HOCHHAUS A, HUGHES T P, et al. Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study [J]. Blood, 2024, 144(Supplement 1): 475-.

[61]YEUNG D T, SHANMUGANATHAN N, YONG A S M, et al. Update of the Ascend-CML Study of Frontline Asciminib: High Rate of Optimal Response and Resistance Due to Mutations Is Rare [J]. Blood, 2024, 144: 476.

[62]ERNST T, RINKE J, LE COUTRE P, et al. The Combination of Asciminib with ATP Competing Tyrosine Kinase Inhibitors Might Overcome the Negative Impact of ASXL1 Mutations on Molecular Response in Newly Diagnosed CML Patients [J]. Blood, 2024, 144: 1774.

[63]ZHOU K, WANG T, PAN L, et al. Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE [J]. Ann Hematol, 2024, 103(10): 4183-91.

[64]LUO J, ZHANG J, LIU L, et al. Efficacy and safety of zanubrutinib monotherapy for chronic lymphocytic leukemia/small lymphocytic lymphoma: A multicenter, real-world study in China [J]. Am J Hematol, 2025, 100(1): 172-5.

[65]QIU L, LIU Z, YI S, et al. Acalabrutinib Versus Chlorambucil Plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia: A Randomized, Multicenter, Open-Label, Phase 3 Study [J]. Blood, 2024, 144: 3251.

[66]YANG S, WEI R, SHI H, et al. The impact of Bruton's tyrosine kinase inhibitor treatment on COVID-19 outcomes in Chinese patients with chronic lymphocytic leukemia [J]. Front Oncol, 2024, 14: 1396913.

[67]LU X, GAO L, QIAN S J, et al. [Single-center study of COVID-19 in patients with chronic lymphocytic leukemia] [J]. Zhonghua Xue Ye Xue Za Zhi, 2024, 45(10): 923-30.

[68]SONG Y, ZHOU K, JING H, et al. Phase 1/2 Studies of DZD8586, a Non-Covalent BBB Penetrant LYN/BTK Dual Inhibitor, in BTK Inhibitor Resistant Chronic Lymphocytic Leukemia (CLL) and Other B-Cell Non-Hodgkin Lymphoma (B-NHL) [J]. Blood, 2024, 144: 3248.

[69] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Multiple Myeloma, Version 1.2025.

[70]https://www.fda.gov/advisory-committees/advisory-committee-calendar/april-12-2024-meeting-oncologic-drugs-advisory-committee-meeting-announcement-04122024：April 12, 2024 Meeting of the Oncologic Drugs Advisory Committee- FDA Presentations .

[71]SONNEVELD P, DIMOPOULOS M A, BOCCADORO M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma [J]. N Engl J Med, 2024, 390(4): 301-13.

[72]FACON T, DIMOPOULOS M A, LELEU X P, et al. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma [J]. N Engl J Med, 2024, 391(17): 1597-609.

[73]FDA Briefing Document. Retrieved March 15, 2024 https://www.fda.gov/media/176986/download.

[74]Mateos MV, et al. 2024 IMS Abstract OA-65.

[75] Albert Oriol, et al.2024 EHA Poster 942.

[76] Leo Rasche,et al.P915 EHA2024 .

[77]HUNGRIA V, ROBAK P, HUS M, et al. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma [J]. N Engl J Med, 2024, 391(5): 393-407.

[78] Pan J, Tan Y, Shan L, Seery S,et al . Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial.[J].Nat Med. 2025 Jan;31(1):126-136.

[79] Hochhaus A, Wang J, Kim DW, Kim DDH, et al. ASC4FIRST Investigators. Asciminib in Newly Diagnosed Chronic Myeloid Leukemia[J]. N Engl J Med. 2024 Sep 12;391(10):885-898.

[80] Yan W, Shi L, Xu J, et al. Clinical implications of residual normal plasma cells within bone marrow across various disease stages in multiple myeloma[J]. Leukemia. 2024 Oct;38(10):2235-2245.

[81] Xu J, Wang BY, Yu SH, et al. Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial[J]. J Hematol Oncol. 2024 Apr 24;17(1):23.

技术支持：乐问医学