Treatment Outcomes for Patients with TP53-Mutated Mantle Cell Lymphoma: A Systematic Review and Meta-Analysis

Abstract

Background TP53 mutation, which is present in 10% to 20% of patients with mantle cell lymphoma (MCL), is the most poor predictor of early disease progression and death for MCL patients. Many clinical trials have been conducted to improve the therapeutic efficacy for these patients, but the best available treatment is still unknown. Thus, we conducted a systematic review and meta-analysis to evaluate the outcome of current various treatments for TP53-mutated (TP53m) MCL.

Methods EMBASE and MEDLINE were searched from inception to December 29, 2023 without language restriction. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies which reported the treatment outcomes for newly diagnosed or relapsed/refractory TP53m MCL patients were included. Outcomes included complete remission (CR) rate, overall response (OR) rate and overall survival (OS).

Results A total of 28 studies which met the inclusion criteria were included in this systematic review and meta-analysis. The treatment approaches for TP53m MCL patients in the included studies contained targeted therapy, targeted therapy combined chemotherapy, hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy. The CR rate and OR rate for TP53m MCL patients with the current treatment was 68% (95%CI 57%-79%, I²=41%) and 79% (95%CI 65%-90%, I²=71%) respectively. For newly diagnosed TP53m MCL patients, targeted therapy was reported to be with the highest CR rate of 79% (95%CI 62%-93%, I²=3%) and the highest OR rate of 96% (95%CI 82%-100%, I²=10%). For relapsed/refractory TP53m patients, CAR-T therapy showed the highest CR rate of 84% (95%CI 64%-98%, I²=43%) and the highest OR rate of 95% (95%CI 73%-100%, I²=62%). The 1-year OS rate and 2-year OS rate for TP53m MCL patients with the current treatment was 63% (95%CI 52%-73%, I²=20%) and 53% (95%CI 38%-69%, I²=44%) respectively. For newly diagnosed TP53m MCL patients, 1-year OS rate and 2-year OS rate for allo-HSCT was 69% (95%CI 50%-83%, I²=54%) and 62% (95%CI 45%-77%, I²=0%), respectively. For relapsed/refractory TP53m MCL patients, 1-year OS rate was 43% (95%CI 10%-82%) for targeted therapy, 61% (95%CI 47%-73%) for CAR-T therapy, and 2-year OS rate was 44% (95%CI 32%-58%) for CAR-T therapy.

Conclusions Although targeted therapy or CAR-T therapy can achieve an relatively high response rate for newly diagnosed or relapsed/refractory TP53m MCL patients, survival was still poor for these patients and more effective treatment strategies need to be exploded.