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:Allogeneic stem cell transplantation after myeloablative conditioning with fludarabine, thiotepa, and cyclophosphamide in relapsed or refractory aggressive B-cell and T-cell lymphomas: results of the prospective ASTRAL study.
Allogeneic stem cell transplantation after myeloablative conditioning with fludarabine, thiotepa, and cyclophosphamide in relapsed or refractory aggressive B-cell and T-cell lymphomas: results of the prospective ASTRAL study.
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尽管异基因干细胞移植(alloSCT)仍是复发T细胞淋巴瘤患者唯一的治愈选择,但其在侵袭性B细胞淋巴瘤治疗流程中的地位正在发生变化。这项多中心、前瞻性、研究者发起的试验研究了在复发/难治性(r/r)侵袭性B细胞或T细胞淋巴瘤患者中,alloSCT前采用由氟达拉滨、塞替派和环磷酰胺(FTC)组成的清髓性预处理方案的有效性和毒性。在60例患者中,1年和2年PFS分别为40%(95% CI 28-52)和36%(95% CI 24-49),OS分别为43%(95% CI 31-56)和37%(95% CI 25-50),42例B细胞淋巴瘤患者与18例T细胞淋巴瘤患者之间无显著差异。
该研究的主要终点定义为1年PFS达到50%,但未达到。B细胞患者2年进展/复发累积发生率为34%(95% CI 19-49),T细胞患者为11%(95% CI 0-26)。NRM累积发生率在第100天为25%(95% CI 14-36),1年时为35%(95% CI 23-47)。12例CAR-T 细胞治疗(CAR-T)失败的患者结局与未接受过CAR-T 的患者相当。在T细胞淋巴瘤中,alloSCT后复发率显著较低,反映出强烈的移植物抗淋巴瘤效应。在B细胞淋巴瘤中,我们的数据提示alloSCT在CAR-T 失败后仍可有效,超过三分之一的患者在两年后处于缓解状态。这些发现支持在侵袭性淋巴瘤患者中继续使用alloSCT。FTC后观察到的显著NRM要求继续寻找耐受性更好的预处理方案。
While allogeneic stem cell transplantation (alloSCT) remains the only curative option for patients with relapsed T-cell lymphoma, its place in the treatment algorithm of aggressive B-cell lymphoma is changing. This multicentre, prospective, investigator-initiated trial investigated the efficacy and toxicity of a myeloablative conditioning regimen comprising fludarabine, thiotepa, and cyclophosphamide (FTC) prior to alloSCT in patients with relapsed/refractory (r/r) aggressive B-cell or T-cell lymphoma. Among 60 patients, PFS at one and two years was 40% (95% CI 28-52) and 36% (95% CI 24-49), OS was 43% (95% CI 31-56) and 37% (95% CI 25-50), respectively, without significant differences between 42 patients with B-cell and 18 patients with T-cell lymphoma.
The primary endpoint of the study defined as 1-year PFS of 50% was not met. The cumulative incidence of progression/relapse at two years was 34% (95% CI 19-49) for B- and 11% (95% CI 0-26) for T-cell patients. Cumulative incidence of NRM was 25% (95% CI 14-36) at day 100 and 35% (95% CI 23-47) at one year.
Twelve patients who had failed CAR T-cell therapy (CART) had outcomes comparable to patients without prior CART. In T-cell lymphoma, relapse after alloSCT was notably low, reflecting a strong graft-versus-lymphomaeffect. In B-cell lymphomas, our data suggest that alloSCT can be effective after CART failure, with more than one-third of patients being in remission after two years.
These findings support the continued use of alloSCT in patients with aggressive lymphomas. Substantial NRM observed after FTC calls for the continued search of better tolerated conditioning regimens.
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