NEGATIVE IMPACT OF THE TP53 GENE MUTATIONS ON THE EFFICACY OF THE THERAPY OF MANTLE CELL LYMPHOMA. INTERIM RESULTS OF THE MCL-2016 PROTOCOL

Abstract

Introduction. The prognosis of mantle cell lymphoma (MCL) is determined by both the intensification of the first-line therapy and the biological characteristics of the tumour.Aim. To assess the MCL incidence rate, as well as the survival rate of MCL patients with TP53 gene mutations.Materials and methods. The prospective study MCL-2016 aimed at identifying TP53 gene mutations was carried out among 24 MCL patients from January 2016 to December 2018. TP53 gene mutations were screened using Sanger sequencing (exons 1(2)–11). No TP53 gene mutations were identified in 20 patients (20 mutp53-), with TP53 gene mutations (4 mutp53 +) being observed in 4 patients.Results. 17 MCL patients (mut p53-) underwent two cycles of R-BAC (rituximab, bendamustine, cytarabine) and two cycles of R-HA (rituximab, cytarabine 12 g/m2 ) with the subsequent transplantation of autologous hematopoietic stem cells. Following therapy, minimum residual disease (MRD) was undetected in all 17 patients, with 3 patients still undergoing therapy. All patients, who completed the therapy, remain in complete remission with a median follow-up of 5 months following the transplantation of autologous hematopoietic stem cells (from 1 to 17 the months). The prognosis in MCL patients with TP53 gene mutations was worse. In the course of this study, two patients with TP53 gene mutations died of progressing MCL in spite of intensive therapy. In two patients with TP53 gene mutation, allogeneic hematopoietic stem cells were transplanted from unrelated completely identical donors. After undergoing the transplantation, the patients are alive and remain in complete remission (observation periods of 3 and 27 months).Conclusion. Following R-BAC/R-HA therapy, all patients from the mutp53- group reached complete clinical and MRDnegative remission, with an acceptable toxicity profile. For MCL patients with TP53 gene mutations, the transplantation of allogeneic hematopoietic stem cells constitutes the only effective treatment.