新诊断或复发/难治性TP53突变套细胞淋巴瘤患者的治疗结局：一项系统评价和荟萃分析。
Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysis.
作者信息
Zhang Na, Xu Jiegang, Luo Chengxin, Xu Rushuang, Zeng Yan, Zeng Dongfeng, Xu Shuangnian, Li Xi
机构信息
Department of Hematology, Chongqing Key Laboratory of Hematology and Microenvironment, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, China.
Department of Hematology, Southwest Hospital, Army Medical University of PLA, Chongqing, China.
出版信息
EClinicalMedicine. 2025 Jul 8;85:103336. doi: 10.1016/j.eclinm.2025.103336. eCollection 2025 Jul.
BACKGROUND
TP53 mutation is a critical predictor of early disease progression and poor prognosis in mantle cell lymphoma (MCL). Optimal treatment for these patients remains unclear. This systematic review and meta-analysis evaluated various strategies for achieving remission in TP53-mutated (TP53m) MCL.
METHODS
We searched EMBASE, MEDLINE and conference proceedings from inception to May 7, 2025, without language restrictions. Randomised controlled trials, single-arm trials, and prospective or retrospective observational studies assessing remission strategies in newly diagnosed or relapsed/refractory TP53m MCL were included. Case reports, case series, and non-human studies were excluded. Two authors independently selected studies, extracted summary data from published reports, and assessed bias risk. Outcomes of interest were complete remission (CR) rate, overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). Random-effects meta-analyses were used for summary estimation. The study is registered with PROSPERO, CRD42024594152.
FINDINGS
A total of 9833 studies were identified, of which 39 studies involving 734 patients with TP53m MCL were eligible. For newly diagnosed TP53m MCL, targeted therapy (TT) had a CR rate of 89% (95% confidence interval (CI) 80-99; n = 52; I = 0%), an ORR of 96% (95% CI 89-100; n = 48; I = 0%), a median OS of 38.5 months (95% CI 37.74-39.26; n = 6), a 2-year OS rate of 76% (19/25) (95% CI 55-91; n = 25), a median PFS of 38.5 months (95% CI 37.74-39.26; n = 6) and a 2-year PFS rate of 62% (95% CI 33-87; n = 30; I = 44%). For relapsed/refractory TP53m MCL, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) had a CR rate of 100% (95% CI 65-100; n = 4; I = 0%) and an ORR of 100% (95% CI 65-100; n = 4; I = 0%); Chimeric antigen receptor-T (CAR-T) cell therapy had a CR rate of 85% (95% CI 69-100; n = 75; I = 66%), an ORR of 90% (95% CI 83-98; n = 67; I = 0%), a 2-year OS rate of 44% (37/61) (95% CI 32-58; n = 61), and 2-year PFS rates of 31% (19/61) (95% CI 20-44; n = 61); TT had a CR rate of 53% (95% CI 39-73; n = 95; I = 60%), an ORR of 64% (95% CI 53-77; n = 139; I = 50%), a median OS of 10.87 months (95% CI 6.41-15.33; n = 57; I = 0%), a 2-year OS rate of 53% (95% CI 45-62; n = 141; I = 0%), a median PFS of 7.83 months (95% CI -0.89-16.55; n = 31; I = 80%) and a 2-year PFS rate of 28% (95% CI 14-44; n = 141; I = 72%).
INTERPRETATION
Our findings indicate that TT may benefit patients with newly diagnosed TP53m MCL, and Allo-HSCT, CAR-T cell therapy, or TT could be considered for relapsed/refractory cases. However, -suboptimal long-term survival highlights the urgent need for innovative therapies. Key limitations, including small sample sizes and few randomised controlled trials (RCTs), emphasize the need for well-designed RCTs with adequate sample size in this field.
FUNDING
The Chongqing Natural Science Foundation and Talent Innovation Capability Cultivation Program of the Army Medical Center.
背景
TP53突变是套细胞淋巴瘤（MCL）早期疾病进展和不良预后的关键预测指标。这些患者的最佳治疗方案仍不明确。本系统评价和荟萃分析评估了TP53突变（TP53m）MCL实现缓解的各种策略。
方法
我们检索了从创刊至2025年5月7日的EMBASE、MEDLINE和会议论文集，无语言限制。纳入评估新诊断或复发/难治性TP53m MCL缓解策略的随机对照试验、单臂试验以及前瞻性或回顾性观察性研究。排除病例报告、病例系列和非人体研究。两位作者独立选择研究，从已发表报告中提取汇总数据，并评估偏倚风险。感兴趣的结局包括完全缓解（CR）率、总缓解率（ORR）、总生存期（OS）和无进展生存期（PFS）。采用随机效应荟萃分析进行汇总估计。该研究已在PROSPERO注册，注册号为CRD42024594152。
结果
共识别出9833项研究，其中39项研究涉及734例TP53m MCL患者符合纳入标准。对于新诊断的TP53m MCL，靶向治疗（TT）的CR率为８９％（95％置信区间（CI）80-99；n = 52；I = 0％），ORR为96％（95％CI 89-100；n = 48；I = 0％），中位OS为38.5个月（95％CI 37.74-39.26；n = 6），2年OS率为76％（19/25）（95％CI 55-91；n = 25），中位PFS为38.5个月（95％CI 37.74-39.26；n = 6），2年PFS率为62％（95％CI 33-87；n = 30；I = 44％）。对于复发/难治性TP53m MCL，异基因造血干细胞移植（Allo-HSCT）的CR率为100％（95％CI 65-100；n = 4；I = 0％），ORR为100％（95％CI 65-100；n = 4；I = 0％）；嵌合抗原受体T（CAR-T）细胞疗法的CR率为85％（95％CI 69-100；n = 75；I = 66％），ORR为90％（95％CI 83-98；n = 67；I = 0％），2年OS率为44％（37/61）（95％CI 32-58；n = 6１），2年PFS率为31％（19/61）（95％CI 20-44；n = 61）；TT的CR率为53％（95％CI 39-73；n = 95；I = 60％），ORR为64％（95％CI 53-77；n = 139；I = 50％），中位OS为10.87个月（95％CI 6.41-15.33；n = 57；I = 0％），2年OS率为53％（95％CI ４５-62；n = 141；I = 0％），中位PFS为7.83个月（95％CI -0.89-16.55；n = 31；I = 80％），2年PFS率为28％（95％CI 14-44；n = 141；I = 72％）。
解读
我们的研究结果表明，TT可能使新诊断的TP53m MCL患者受益，对于复发/难治性病例可考虑Allo-HSCT、CAR-T细胞疗法或TT。然而，长期生存欠佳凸显了对创新疗法的迫切需求。包括样本量小和随机对照试验（RCT）少在内的关键局限性，强调了该领域需要设计良好且样本量充足的RCT。
资助
重庆自然科学基金和陆军军医大学人才创新能力培养计划。
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