Epoetin beta

“那些治疗成功的病例会逐渐淡出关注，而难治、复发的病例却总让人记挂 —— 单一形态上皮亲肠道 T 细胞淋巴瘤（MEITL）带来的困境，正是如此。” 作为原发胃肠道 T 细胞淋巴瘤里的罕见侵袭性亚型，MEITL 不仅早期诊断时容易 “隐匿踪迹”，对常规化疗的反应率也极低，患者预后往往不尽如人意。 韩国首尔圣玛丽医院团队针对 MEITL 开展的回顾性研究，为这类难治疾病的治疗打开了新窗口 —— 研究明确，异基因造血干细胞移植（allo-HSCT）在改善 MEITL 患者预后方面发挥着关键作用，为临床应对这一难题提供了重要的治疗方向。 📖 发表期刊： Front Oncol 01 MEITL 易被忽视的凶险肠道淋巴瘤 MEITL 曾被归为肠病相关 T 细胞淋巴瘤（EATL）2 型，2016 年世界卫生组织（WHO）分类将其重新定义为独立的外周 T 细胞淋巴瘤亚型。与多见于西方人群、常伴乳糜泻的 EATL 不同，MEITL 在亚洲人群中更为常见，且与乳糜泻无关联，病理上也缺乏典型 EATL 那样的炎症背景和明显坏死，这些特点使其在诊断时容易与其他肠道疾病混淆。 从临床表现来看，MEITL 几乎没有特异性症状，患者常以腹痛、体重下降、食欲不振、腹胀、腹泻等常见胃肠道不适就诊，部分患者还会出现消化道出血，少数人甚至没有明显症状，仅在体检时偶然发现。这种 “普通” 的症状表现，导致很多患者在确诊时已处于疾病晚期，错过最佳治疗时机。 在该研究纳入的 35 例患者中，65.7% 因急性腹痛就医，其中 60% 与肠穿孔相关，17.1% 合并肠梗阻；85.7% 的患者需要通过手术才能明确诊断，仅有 14.3% 能通过内镜检查确诊，足见其诊断难度。 在疾病分期与风险评估上，MEITL 进展迅速的特点也十分突出。按照 Lugano 淋巴瘤分期标准，57.1% 的患者确诊时已达 IV 期，肿瘤累及横膈上淋巴结或肺、骨髓等结外器官；加上 II₂ 期和 II₂E 期患者，82.9% 的患者属于晚期疾病。 从预后评分来看，37.1% 的患者国际预后指数（IPI）为低风险，22.9% 为高风险；T 细胞淋巴瘤预后指数（PIT）中，11.4% 的患者为高风险，这些数据都预示着患者整体治疗难度较大。 02 常规化疗疗效有限，预后惨淡 由于 MEITL 发病率低，目前尚无统一的标准治疗方案，临床常用的化疗方案主要围绕蒽环类、异环磷酰胺类和铂类药物展开，但整体治疗效果并不理想。 蒽环类药物方案是血液肿瘤治疗中的经典方案，包括 CHOP（环磷酰胺、阿霉素、长春新碱、泼尼松）、CHOEP（CHOP 联合依托泊苷）、EPOCH（依托泊苷、阿霉素、长春新碱持续输注联合环磷酰胺、泼尼松）、ProMACE/CytaBOM 等。 在该研究中，18 例患者采用这类方案作为一线治疗，仅 3 例（16.7%）达到完全缓解（CR），且接受 CHOP 或 CHOEP 方案的患者中，无 1 例实现 CR，显示出蒽环类方案对 MEITL 的疗效局限性。 异环磷酰胺类方案包括 SMILE（地塞米松、甲氨蝶呤、异环磷酰胺、左旋门冬酰胺酶、依托泊苷）、DL-ICE（地塞米松、左旋门冬酰胺酶联合 ICE 方案）等，在 MEITL 治疗中表现相对更优。 研究中 13 例患者采用该类方案，在所有达到 CR 的 10 例患者中，有 7 例接受的是异环磷酰胺类方案，成为目前一线治疗中较有潜力的选择。 铂类药物方案以 DHAP（地塞米松、大剂量阿糖胞苷、顺铂）为代表，研究中仅 1 例患者使用该方案，且在治疗 17 天后因腹腔脓肿引发的感染性休克死亡，暂无法判断其在 MEITL 常规治疗中的价值。 在一线治疗失败后的挽救治疗中，效果同样不佳，仅有 6/18 例患者（33.3%）达到 CR。在这 6 例患者中，3 例接受了 DL-ICE，而另外 3 例接受了 ESHAP 作为挽救治疗。 从整体预后数据来看，MEITL 患者的生存状况令人担忧。该研究中，患者的中位总生存期（OS）仅 12.1 个月，1 年 OS 率为 50.9%，5 年 OS 率更是低至 13.3%；1 年无进展生存期（PFS）率为 36.3%，5 年 PFS 率仅 13.8%。 在接受一线治疗的 32 例患者中，4 例（12.5%）未完成疗效评估即死亡，18 例（56.2%）出现疾病进展（PD），仅 10 例（31.3%）达到 CR；而在达到 CR 的患者中，后续又有 6 例（60%）出现复发，进一步凸显了常规化疗的局限性。 03 造血干细胞移植 异基因移植成关键突破口 面对常规化疗的困境，造血干细胞移植成为探索 MEITL 治疗新路径的重要方向。研究对比了自体造血干细胞移植（auto-HSCT）和异基因造血干细胞移植（allo-HSCT）的疗效，发现两者在改善患者预后上存在显著差异。 自体造血干细胞移植在血液肿瘤巩固治疗中应用广泛，但在 MEITL 治疗中效果有限。研究中，10 例达到 CR 的患者里，4 例选择一线巩固自体移植，但这 4 例患者后续全部复发，并最终因疾病进展死亡；在复发或进展的患者中，1 例接受挽救性自体造血干细胞移植联合细胞因子诱导杀伤细胞输注，虽实现无进展生存，但属于个例。整体来看，自体造血干细胞移植患者的复发率高达 80%，对 MEITL 患者长期生存的改善作用并不明显。 与自体造血干细胞移植形成鲜明对比的是，异基因造血干细胞移植展现出显著的治疗优势。在一线巩固异基因移植方面，3 例达到 CR 后接受该治疗的患者，在最后随访时均维持 CR 状态，其中 1 例随访时间长达 61.3 个月，1 例随访 33.2 个月，长期生存效果显著。 在挽救性异基因造血干细胞移植方面，6 例复发或进展的患者接受该治疗，2 例达到 CR 并长期生存，其中 1 例随访时间达 139.1 个月，即使部分患者因感染性休克死亡，仍在死亡时维持 CR 状态，显示出异基因造血干细胞移植对肿瘤的强大控制能力。 从整体数据对比来看，接受异基因造血干细胞移植的患者 5 年 OS 率为 46.9%，5 年 PFS 率为 50.8%；未接受移植的患者 5 年 OS 和 PFS 率均为 0；自体造血干细胞移植患者 5 年 OS 和 PFS 率仅为 20%。 同时，异基因造血干细胞移植患者的治疗相关死亡率（TRM）为 12.5%，低于未移植组的 90.5%，这些数据充分证明了异基因造血干细胞移植在 MEITL 治疗中的核心价值。 在（A）总生存率（OS）和（B）无进展生存率（PFS）方面，接受异基因造血干细胞移植患者的结局显著优于接受其他治疗的患者。 接受自体造血干细胞移植的患者，其（C）累积复发率（CIR）最高；而未接受造血干细胞移植组患者，其（D）治疗相关死亡率（TRM）最高。 当然，异基因造血干细胞移植也存在一定风险，最主要的是移植物抗宿主病（GVHD）和感染。研究中，44.4% 的患者出现急性 GVHD，中位发病时间为 32.5 天，部分患者表现为皮肤、肠道受累，需激素冲击治疗；67.3% 的患者出现慢性 GVHD，中位发病时间为 5.9 个月，主要累及口腔、眼睛，少数累及肝脏、肺部。 不过，通过规范的预处理方案（如氟达拉滨 30mg/m² 连续 6 天 + 马法兰 70mg/m² 1 天 + 分次全身放疗 800cGy）和 GVHD 预防措施（如抗胸腺细胞球蛋白），多数并发症可得到控制，研究中无 1 例患者因 GVHD 死亡。 04 MEITL  治疗的预后影响因素与临床建议 通过对研究数据的深入分析，可明确影响 MEITL 患者预后的关键因素，为临床治疗决策提供参考。其中，诊断时的体力状态（ECOG 评分）是重要影响因素，ECOG 评分 2-4 分的患者 OS 和 PFS 显著更差，风险比（HR）分别为 3.727 和 2.862，提示体力状态差的患者治疗耐受性更低，预后更差。中期治疗反应也至关重要，中期 FDG-PET/CT Deauville 评分为 5 分（提示混合反应、稳定或进展）的患者，TRM 显著升高（HR=4.388），说明及时评估治疗反应并调整方案，对降低死亡风险十分重要。此外，IPI 高风险组患者在单变量分析中 OS 和 TRM 更差，但在多变量分析中无统计学意义；年龄、PIT 评分等对生存无显著影响，这些结果为临床风险分层提供了依据。 基于以上研究结果，结合 MEITL 的疾病特点，可提出以下临床治疗建议。 在诊断与评估环节，临床医生需对不明原因腹痛、腹泻、体重下降的患者保持高度警惕，尤其是症状持续不缓解或伴随消化道急症（如穿孔、梗阻）时，需及时通过影像学、内镜及病理检查明确诊断，同时完善分期检查和体力状态评估，尽早识别 MEITL 患者。 在一线治疗选择上，应优先考虑异环磷酰胺类方案（如 DL-ICE、SMILE），以提高 CR 率，为后续移植创造条件，避免将 CHOP 或 CHOEP 作为首选方案。 在移植时机与类型选择上，患者达到 CR 后，应优先推荐一线巩固异基因移植；对于复发或进展的患者，需积极开展挽救治疗，争取达到 PR 或 CR 后尽早进行挽救性异基因造血干细胞移植，不建议优先选择 自体造血干细胞移植。在长期管理上，移植后需密切监测 GVHD 和感染等并发症，定期通过 FDG-PET/CT 评估疾病状态，及时处理复发或进展情况，尽可能延长患者生存时间。 自体移植还是异基移植？ 鉴于单形性亲上皮性肠道 T 细胞淋巴瘤（以下简称肠道 T）的侵袭性，仅靠化疗很难无限期维持完全缓解（CR）状态，自体造血干细胞移植（Auto-HSCT）应与强化化疗一并作为巩固治疗加以考虑。 实际上，研究团队最初的治疗策略也是如此：对于达到完全缓解、病情高危但身体能耐受的患者，先选择观察或自体造血干细胞移植，等疾病复发后再考虑异基因造血干细胞移植（allo-HSCT）。 但肠道 T 的恶性度实在太高，病情进展又快，之前的策略行不通 —— 很多患者根本没机会等到复发再做异基因移植，疾病就已经快速进展了。所以调整了思路，现在只要患者达到首次完全缓解，就会尽快安排异基因造血干细胞移植。这也意味着，一线治疗不能再依赖环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）方案，像以异环磷酰胺或铂类为基础的化疗方案可能更合适。这类方案能尽量控制肿瘤，为符合条件的患者争取后续异基因移植的机会，这对肠道 T 治疗或许有更大价值。 在文献提到的病例中，已有 7 位肠道 T 患者接受了异基因造血干细胞移植，截至最后一次随访，其中 5 位仍保持着完全缓解状态。 总结 尽管异基因造血干细胞移植为 MEITL 治疗带来了希望，但该疾病的治疗仍面临诸多挑战，未来还需从多方面开展深入研究。在诊断优化方面，MEITL 目前缺乏特异性分子标志物，未来可进一步探索其基因组特征，如 SETD2 突变、SYK 表达异常等，寻找更精准的诊断指标，实现早期诊断，避免误诊、漏诊。 在新药研发方面，针对 MEITL 相关的信号通路异常（如 JAK/STAT 通路），研发 JAK 抑制剂、WEE1 激酶抑制剂等新型靶向药物，与化疗或移植联合使用，进一步提高治疗效果，降低复发率。 在移植方案改进方面，探索更安全、有效的预处理方案和 GVHD 预防策略，降低异基因造血干细胞移植的并发症发生率，扩大移植适应证，让更多体力状态较差或老年患者能从该治疗中获益。 在临床研究设计方面，由于 MEITL 罕见，单中心研究样本量有限，未来需开展多中心、大样本临床研究，验证现有治疗方案的有效性，同时探索新的治疗模式，如靶向药物联合免疫治疗、细胞治疗等，为 MEITL 患者提供更多治疗选择。 参考文献 Min GJ, Oh YE, Jeon Y, et al. Front Oncol. 2024 Nov 21;14:1388623. ●扫码可直接下载文献原文● 撰稿作者    洪 飞 淋巴瘤之家  创始人 我是霍奇金淋巴瘤患者，目前康复15年——“全世界这么多人，这么多种病，为什么偏偏是我得了淋巴瘤，后来我觉得，或许，是淋巴瘤特意选择了我，让我能带着亲身经历，站在病友的最前线，给大家多一份支撑。” 我在日常和治疗不顺利的病友交流中，总会有人问有没有人用过这个方案，效果怎么样，我总是一时语塞不知道怎么回答，因为病友们总是想看到更鲜活的例子，才有信心再走下去，而不仅仅是数据报道。 因此我萌发了一个想法：收集那些在我们日常工作中遇到的病情较重病友的康复案例和最新文献，给予相似的病友一定信心上的鼓励，CR086就此诞生了。 END 供稿：洪飞  | 排版：蒲蝶   声明：本文中涉及的信息仅供淋巴瘤病友及家属交流参考，不作为用药推荐，具体诊疗方案请遵从专业医生的意见或指导。 关注一下  抗瘤少走弯路

FOSTER CITY, Calif.--(BUSINESS WIRE)--Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced presentations on RYTELO® (imetelstat) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2025 Congress. Together, the presentations reinforce the potential benefits of the first-in-class oligonucleotide telomerase inhibitor RYTELO for a range of patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia and showcase the progress Geron is making with the ongoing IMpactMF and IMproveMF trials of imetelstat in myelofibrosis (MF). “Transfusion independence is an important goal for LR-MDS patients, but one that historically has not been achievable for many,” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center. “While imetelstat is already playing a vital role in LR-MDS, these new analyses being presented at ASCO and EHA reinforce its potential to give a broad range of patients more time without transfusions and should also give clinicians confidence to add it to their toolkit as a second-line option for eligible patients.” Presentations at ASCO and EHA include: New pooled, post-hoc analyses expand on the pivotal IMerge results across challenging LR-MDS subpopulations Analysis of patients with ring sideroblast negative (RS-) disease, showing that these difficult-to-treat patients appeared to experience clinical benefit with RYTELO, including ≥8-week, ≥24-week and ≥1-year red blood cell transfusion independence (RBC-TI), duration of RBC-TI, and hemoglobin rise in patients who achieved RBC-TI, consistent with prior findings from the overall Phase 3 IMerge population. Analysis showing clinical benefit with RYTELO regardless of baseline serum erythropoietin (sEPO) level, supporting the use of RYTELO in the frontline setting for LR-MDS patients ineligible for erythropoiesis-stimulating agents (ESAs), and in the second-line setting after ESAs regardless of sEPO. Analysis showing clinical benefit with RYTELO in ESA-ineligible or relapsed/refractory patients regardless of prior treatment with luspatercept or lenalidomide. Patients who had prior treatment with a hypomethylating agent (HMA) showed modest clinical activity with RYTELO. Patient-centric outcome measures offering deeper insight on RYTELO impact in new post-hoc analyses from Phase 3 IMerge trial Analysis showing that certain RYTELO-treated patients experienced sustained improvements in health-related quality-of-life (QOL) compared with placebo, as measured by certain categories in the patient-reported QOL in Myelodysplasia Scale (QUALMS) instrument. Exploratory analysis suggesting that certain patients treated with RYTELO experienced a longer mean duration of time without transfusion reliance or relapse (TWiTR), compared with placebo. New updates on ongoing trials in MF Recently updated preliminary data from the dose escalation portion of the Phase 1/1b IMproveMF trial showing the combination of imetelstat and ruxolitinib was generally well-tolerated, with no dose-limiting toxicities observed as of the data cutoff date, and encouraging early dose-dependent efficacy data suggesting the potential of the combination for patients with intermediate-1 (INT-1), intermediate-2 (INT-2) or high-risk (HR) MF. Trial-in-progress (TiP) update on the Phase 3 IMpactMF trial investigating imetelstat in relapsed/refractory MF, reporting that the trial has met approximately 80% of its enrollment target as of February 2025. “At ASCO and EHA, we’re excited to present new analyses on how RYTELO can deliver meaningful benefit across a range of LR-MDS patients who otherwise may have had limited options, whether due to their ring sideroblast status, baseline EPO level, or their treatment history,” said Faye Feller, M.D., Executive Vice President and Chief Medical Officer of Geron. “We believe the depth and breadth of our data reinforce the potential of RYTELO to address critical unmet needs in LR-MDS and, combined with the advances we are making with our myelofibrosis program, underscore our confidence in telomerase inhibition as a potentially transformative clinical strategy and our commitment to exploring its full potential.” See below for a full schedule of presentations at ASCO and EHA. ASCO 2025 Presentations Presentation Title Author Abstract Number Presentation Details IMproveMF update: phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF) John O. Mascarenhas, M.D. #6515 Rapid Oral, Fri. May 30, 1:00-2:30 PM CDT Effect of prior treatment (tx) on the clinical activity of imetelstat (IME) in transfusion- dependent (TD) patients (pts) with erythropoiesis-stimulating agent (ESA), relapsed or refractory (R/R)/ineligible lower-risk myelodysplastic syndromes (LR-MDS) Rami S. Komrokji, M.D. #6569 Poster, Sun. June 1, 9:00 AM-12:00 PM CDT IMpactMF, randomized, open-label, phase 3 trial of imetelstat (IME) versus best available therapy (BAT) in patients (pts) with intermediate-2 (INT-2) or high-risk (HR) myelofibrosis (MF) relapsed or refractory (R/R) to Janus kinase inhibitors (JAKi) John O. Mascarenhas, M.D. #TPS6588 Poster, Sun. June 1, 9:00 AM-12:00 PM CDT EHA 2025 Presentations Presentation Title Author Abstract Number Presentation Details Increased Duration of Time Without Transfusion Reliance (TWiTR) For Patients with LR-MDS Treated with Imetelstat Versus Placebo in the IMerge Trial Mikkael A. Sekeres, M.D. #PF646 Poster, Fri. June 13, 18:30-19:30 CEST IMproveMF Update: Phase 1/1B Trial of Imetelstat + Ruxolitinib in Patients with INT-1, INT-2, or High-Risk MF John O. Mascarenhas, M.D. #PF830 Poster, Fri. June 13, 18:30-19:30 CEST IMpactMF: Randomized, Open-Label, Phase 3 Trial of Imetelstat vs Best Available Therapy in Patients with INT-2 or High-Risk MF Relapsed/Refractory to JAK Inhibitors John O. Mascarenhas, M.D. #PF841 Poster, Fri. June 13, 18:30-19:30 CEST Health-related Quality of Life Outcomes in Patients with Lower-Risk Myelodysplastic Syndromes Treated with Imetelstat in the IMerge Trial María Díez-Campelo, M.D., Ph.D. #PS1639 Poster, Sat. June 14, 18:30-19:30 CEST Outcomes of Imetelstat Therapy in RS-Negative LR-MDS from the Pooled IMerge Study Populations Valeria Santini, M.D. #PS1622 Poster, Sat. June 14, 18:30-19:30 CEST Outcomes with Imetelstat by Serum Erythropoietin Levels in Patients with LR-MDS Who Were Treatment Naïve or Who Had Prior Treatment with Erythropoiesis-Stimulating Agents Rami S. Komrokji, M.D. #PS1640 Poster, Sat. June 14, 18:30-19:30 CEST Characterization and Management of Transient Cytopenias Associated with Imetelstat in LR-MDS from the IMerge Trial Amer M. Zeidan, M.D. #PB2760 Publication-only Please see the full presentations for important qualifications and limitations on these post-hoc analyses. About RYTELO® (imetelstat) RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks. In addition, RYTELO is approved in the European Union as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration and the European Commission. About Geron Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO® (imetelstat) is approved in the United States and the European Union for the treatment of certain adult patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or LinkedIn. US IMPORTANT SAFETY INFORMATION ABOUT RYTELO® WARNINGS AND PRECAUTIONS Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO. Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended. Neutropenia RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO. Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended. Infusion-Related Reactions RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion. Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended. Embryo-Fetal Toxicity Based on animal findings, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose. ADVERSE REACTIONS Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%). Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf. The Summary of Product Characteristics (SmPC) for RYTELO in the EU is available at https://pi.geron.com/products/rytelo/eu/rytelo_smpc_eu.pdf Use of Forward-Looking Statements Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) that the new analyses presented at ASCO and EHA reinforce the potential benefits of RYTELO for a range of patients with LR-MDS with transfusion-dependent anemia, including its potential to give a broad range of patients more time without transfusions and should support clinician’s confidence in RYTELO as a second-line option for eligible patients; (ii) beliefs regarding imetelstat’s vital role in LR-MDS, (iii) how RYTELO can deliver meaningful benefit across a range of LR-MDS patients who otherwise may have had limited options, whether due to ring sideroblast status, baseline EPO levels, or their treatment history; (iv) Geron’s beliefs that the depth and breadth of its data reinforce the potential of RYTELO to address critical unmet needs in LR-MDS and regarding telomerase inhibition as a potentially transformative clinical strategy; and (v) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron is successful in commercializing RYTELO (imetelstat) for the treatment of certain patients with LR-MDS with transfusion dependent anemia and achieves market acceptance across the breadth of the eligible patient segments in RYTELO’s approved indication; (b) whether the FDA and European Commission will approve imetelstat for other indications on the timelines expected, or at all; (c) Geron’s plans to commercialize RYTELO in the European Union, or EU and risks related to operating outside of the U.S.; (d) whether Geron overcomes potential delays and other adverse impacts that may be caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for and meet expected timelines and planned milestones; (e) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (f) whether any future safety or efficacy results of RYTELO treatment cause its benefit-risk profile to become unacceptable; (g) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (h) whether Geron meets its post-marketing requirements and commitments for RYTELO; (i) whether there are failures or delays in manufacturing or supplying sufficient quantities of RYTELO (imetelstat) or other clinical trial materials that impact commercialization of RYTELO or the continuation of its ongoing clinical trials, including the IMpactMF trial; (j) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; and (k) whether Geron stays in compliance with and satisfies its obligations under its debt and synthetic royalty financing agreements. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 2025, and subsequent filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances.