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:The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia.
The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia.
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我们回顾性评估了47例TP53突变型急性淋巴细胞白血病(ALL)成人患者的治疗结局,这些患者接受过blinatumomab、inotuzumab和/或CD19 CAR-T 细胞疗法。接受blinatumomab(n=46)、inotuzumab(n=26)及CD19 CAR-T 细胞(n=6)治疗后的完全缓解(伴或不伴血细胞计数恢复,CR/CRi)率及微小残留病(MRD)阴性率分别为58.7%(96.3%)、61.5%(60%)和66.7%(75%)。全体患者中位总生存期(OS)为13.6个月(95% CI:9.6–17.2),不同新型挽救治疗间无显著差异(p=0.40)。对blinatumomab、InO和CAR-T 细胞有应答者的12个月无白血病生存率(LFS)分别为20%、11%和0%(p=0.743)。应答后接受异基因造血干细胞移植(HSCT)的患者,其12个月LFS优于未接受移植者(35% vs. 9%,p=0.014)。在blinatumomab治疗后复发的患者中,11例(61%)出现CD19阴性疾病。
因此,靶向和免疫治疗可使携带TP53突变的B细胞ALL成人患者获得较高的MRD阴性缓解率。然而,若不进行异基因HSCT巩固治疗,缓解持续时间较短;blinatumomab治疗后复发常表现为CD19阴性疾病。
We retrospectively evaluated the treatment outcomes of 47 adult patients with TP53-mutated acute lymphoblastic leukaemia (ALL) treated with either blinatumomab, inotuzumab or/and CD19 CAR T-cell therapy. The complete remission with or without count recovery (CR/CRi) (negative minimal residual disease (MRD-) rate) following treatment with blinatumomab (n = 46), inotuzumab (n = 26) and CD19 CAR T cells (n = 6) was 58. 7% (96. 3%), 61. 5% (60%) and 66. 7% (75%) respectively. The median OS was 13. 6 months (95% CI: 9. 6-17. 2) for all patients, and it was not significantly different based on the individual novel salvage therapy (p = 0. 40).
The 12-month leukaemia-free survival (LFS) for responders to blinatumomab, InO and CAR T cells was 20%, 11% and 0% (p = 0. 743) respectively. Patients who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) post-response had improved 12-month LFS compared to those who did not (35% vs. 9%, p = 0. 014). Among relapsed patients following blinatumomab, 11 (61%) presented with CD19-negative disease.
Hence, targeted and immune-based therapies are effective in inducing high MRD-negative remission rates in adults with B-cell ALL harbouring TP53 mutations. Nonetheless, the durability of remission is short in the absence of allogeneic HCT consolidation and relapse frequently manifested as CD19-negative disease following blinatumomab.
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