Outcomes of Wild Type and TP53-Mutated B Cell Malignancy Patients Receiving CAR-T Cell Therapy: A Systematic Review and Meta-Analysis

Abstract

P53 mutation (TP53m) is a common intrinsic factor involved in relapsed or refractory (R/R) B cell malignancies that associates with treatment resistance. As a novel immunotherapy, CAR-T has been increasingly applied in TP53m B cell malignancies, yet whether it can overcome the poor outcome of the TP53m population is controversial. We searched MEDLINE and EMBASE to identify population-based cohort studies that evaluated the CAR-T treatment outcomes between wild type and TP53m patients in B cell malignancies. Meta-analysis on their complete response (CR), partial response (PR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) was carried out and pooled risk ratios (RR) or hazard ratios (HR) were estimated. A total of 10 eligible studies reporting 848 patients with B cell malignancies from wild type and TP53m groups receiving CAR-T therapy were selected. The CR and ORR were comparable in both wild type and TP53m patients either with B cell lymphoma or leukaemia (all p > 0.05). However, the TP53m group was associated with shorter PFS and OS in both diseases (all p < 0.05). In traditional single targeting CAR-T therapy, the PFS and OS were shorter in the TP53m group than in the wild type group (all p < 0.05). In contrast, the former outcomes of the wild type and TP53m groups were comparable when receiving dual-targeting CAR-T treatment (all p > 0.05). Though the CR and ORR of wild type and TP53m groups were similar, the PFS and OS of B cell malignancy patients bearing TP53m were inferior to wild type patients receiving CAR-T cell treatment. Notably, the CR, PFS and OS of wild type and TP53m groups exhibit the same therapeutic effect via CD19/22 CAR-T cocktail therapy. In other words, the poor prognosis of TP53m patients may be overcome by double targeting CAR-T mode.