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靶向与免疫治疗在 TP53 突变成人急性淋巴细胞白血病中的疗效

英文原题:The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia.

查看英文原题

The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia.

PubMed 2025/09/01(内容时间) Br J Haematol Q2 · IF 3.6(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Pourhassan H、Tinajero J、Ma H、Jackson R、Pillai R、Ngo D、Agrawal V、Koller P
单位
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, USA.United States
期刊
British journal of haematology2025 Oct
原文标识
PubMed 40890465 · DOI 10.1111/bjh.20260