Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context

Summary: 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-mutat...

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Main Authors: Na Zhang, Jiegang Xu, Chengxin Luo, Rushuang Xu, Yan Zeng, Dongfeng Zeng, Shuangnian Xu, Xi Li
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:EClinicalMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589537025002688
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author Na Zhang
Jiegang Xu
Chengxin Luo
Rushuang Xu
Yan Zeng
Dongfeng Zeng
Shuangnian Xu
Xi Li
author_facet Na Zhang
Jiegang Xu
Chengxin Luo
Rushuang Xu
Yan Zeng
Dongfeng Zeng
Shuangnian Xu
Xi Li
author_sort Na Zhang
collection DOAJ
description Summary: 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; I2 = 0%), an ORR of 96% (95% CI 89–100; n = 48; I2 = 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; I2 = 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; I2 = 0%) and an ORR of 100% (95% CI 65–100; n = 4; I2 = 0%); Chimeric antigen receptor-T (CAR-T) cell therapy had a CR rate of 85% (95% CI 69–100; n = 75; I2 = 66%), an ORR of 90% (95% CI 83–98; n = 67; I2 = 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; I2 = 60%), an ORR of 64% (95% CI 53–77; n = 139; I2 = 50%), a median OS of 10.87 months (95% CI 6.41–15.33; n = 57; I2 = 0%), a 2-year OS rate of 53% (95% CI 45–62; n = 141; I2 = 0%), a median PFS of 7.83 months (95% CI -0.89–16.55; n = 31; I2 = 80%) and a 2-year PFS rate of 28% (95% CI 14–44; n = 141; I2 = 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.
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spelling doaj-art-b3d6c804a6d141dc86fa641123d104f32025-08-20T03:50:26ZengElsevierEClinicalMedicine2589-53702025-07-018510333610.1016/j.eclinm.2025.103336Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in contextNa Zhang0Jiegang Xu1Chengxin Luo2Rushuang Xu3Yan Zeng4Dongfeng Zeng5Shuangnian Xu6Xi Li7Department of Hematology, Chongqing Key Laboratory of Hematology and Microenvironment, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, ChinaDepartment of Hematology, Southwest Hospital, Army Medical University of PLA, Chongqing, ChinaDepartment of Hematology, Southwest Hospital, Army Medical University of PLA, Chongqing, ChinaDepartment of Hematology, Chongqing Key Laboratory of Hematology and Microenvironment, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, ChinaDepartment of Hematology, Chongqing Key Laboratory of Hematology and Microenvironment, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, ChinaDepartment of Hematology, Chongqing Key Laboratory of Hematology and Microenvironment, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, China; Corresponding author.Department of Hematology, Southwest Hospital, Army Medical University of PLA, Chongqing, China; Corresponding author.Department of Hematology, Chongqing Key Laboratory of Hematology and Microenvironment, Army Medical Center, Daping Hospital, Army Medical University of PLA, Chongqing, China; Corresponding author.Summary: 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; I2 = 0%), an ORR of 96% (95% CI 89–100; n = 48; I2 = 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; I2 = 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; I2 = 0%) and an ORR of 100% (95% CI 65–100; n = 4; I2 = 0%); Chimeric antigen receptor-T (CAR-T) cell therapy had a CR rate of 85% (95% CI 69–100; n = 75; I2 = 66%), an ORR of 90% (95% CI 83–98; n = 67; I2 = 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; I2 = 60%), an ORR of 64% (95% CI 53–77; n = 139; I2 = 50%), a median OS of 10.87 months (95% CI 6.41–15.33; n = 57; I2 = 0%), a 2-year OS rate of 53% (95% CI 45–62; n = 141; I2 = 0%), a median PFS of 7.83 months (95% CI -0.89–16.55; n = 31; I2 = 80%) and a 2-year PFS rate of 28% (95% CI 14–44; n = 141; I2 = 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.http://www.sciencedirect.com/science/article/pii/S2589537025002688Mantle cell lymphomaTP53 mutationsRemission strategies
spellingShingle Na Zhang
Jiegang Xu
Chengxin Luo
Rushuang Xu
Yan Zeng
Dongfeng Zeng
Shuangnian Xu
Xi Li
Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context
EClinicalMedicine
Mantle cell lymphoma
TP53 mutations
Remission strategies
title Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context
title_full Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context
title_fullStr Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context
title_full_unstemmed Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context
title_short Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysisResearch in context
title_sort treatment outcomes for patients with newly diagnosed or relapsed refractory tp53 mutated mantle cell lymphoma a systematic review and meta analysisresearch in context
topic Mantle cell lymphoma
TP53 mutations
Remission strategies
url http://www.sciencedirect.com/science/article/pii/S2589537025002688
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