CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Novelties on Multiple Myeloma from the Main 2024 Hematology Conferences.
Novelties on Multiple Myeloma from the Main 2024 Hematology Conferences.
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尽管近年来引入了多种疗法,多发性骨髓瘤(MM)因其极高的患者间和患者内异质性,仍是一种难以治疗的血液系统恶性肿瘤。然而,在2024年主要国际会议上,出现了非常显著的新方法数据,这些方法即使在高危或非常晚期疾病中也能改善结局。包含抗CD38单克隆抗体的前期四联方案,在可移植和不可移植患者中,均被证明在缓解深度和长期疗效方面是最佳疗法,而MRD评估可能在确定治疗持续时间、避免不必要的过度治疗方面发挥关键作用。
然而,四联方案也无法克服高危细胞遗传学或循环肿瘤细胞的负面预后价值;因此,对于具有这些特征的患者,将不得不评估替代方法。
此外,考虑到并非所有患者,尤其是老年和体弱患者,都能接受此类治疗,因此有必要提高为每位患者识别最合适疗法的能力。双特异性抗体和CAR-T 细胞代表了晚期MM治疗的新前沿。
然而,它们在早期复发和功能性高危患者中显示出更高的疗效和更低的毒性。在前线治疗中,纳入新型免疫疗法所获得的结果极具前景。在复发/难治性MM患者中,belantamab mafodotin和CELMoDs等药物与蛋白酶体抑制剂或免疫调节剂联合,可能代表另一种有效选择。
Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity.
However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment.
However, quadruplets also fail to overcome the negative prognostic value of high-risk cytogenetics or circulating tumour cells; therefore, in patients with these features, alternative approaches will have to be evaluated.
Moreover, considering that not all patients, particularly older and frail ones, will be able to undergo such therapies, it will be necessary to refine the ability to identify the most appropriate therapy for each patient. Bispecific antibodies and CAR-T cells represent the new frontier in the treatment of advanced MM.
However, they have shown even more efficacy with less toxicity in early relapses and functional high-risk patients. In the upfront setting, the results obtained with the inclusion of novel immunotherapies are extremely promising. In relapsed/refractory MM patients, agents such as belantamab mafodotin and CELMoDs, in combination with proteasome inhibitors or immunomodulatory agents, may represent another valid option.
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