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RESULTS OF TREATMENT PATIENTS OF MANTLE CELL LYMPHOMA DEPENDING ON THE MUTATIONAL STATUS OF THE TP53 GENE

PB2016

Koroleva, D.1; Zvonkov, E.1; Gabeeva, N.1; Smolyaninova, A.1; Gavrilina, O.1; Shchetsova, O.1; Biderman, B.1; Tsygankova, S.2; Bulygina, E.2; Rastorguev, S.2; Nedoluzhko, A.2; Sudarikov, A.1; Kovrigina, A.1; Galtseva, I.1; Obukhova, T.1; Kuzmina, L.1; Parovichnikova, E.1; Savchenko, V.1

doi: 10.1097/01.HS9.0000566556.36343.8f
Publication Only: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Free

1National Medical Research Center for Hematology

2National Research Center “Kurchatov institute”, Moscow, Russian Federation

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Background:

According to a retrospective study published data in 2017 by the Nordic MCL group, in multivariable analyses, only mutation TP53 showed independent prognostic impact. The median OS for the TP53-mutated cases was 1.8 years, median PFS was 0.9 years.

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Aims:

To assess the incidence of TP53 gene mutation and survival in pts with MCL during of prospective trial MCL-RUS-2016.

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Methods:

A total 25 pts were enrolled in prospective study MCL-RUS-2016 between 2016 to 2019 years. The median age was 52 years (range, 33 to 71 years). Seven pts (28%) were over the age of 60 years. Male:female = 15:10. In all pts the Ann Arbor stage was 4. Among 25 pts in depend pretreatment MIPI score, 36%, 48% and 16%, respectively, were considered as being at low, intermediate and high risk. Seven (28%)of 25 pts had blastoid MCL. Mutation of the TP53 gene determined using by Sanger sequencing of the coding region (exons 1(2)-11) was present in 4 (16%) pts (TP53mut). Another 21 pts (84%) had wild type mutational status (TP53 wt). Complex karyotype (CK) was indentified in 8 (32%) pts. Three pts had the mutation of p53 and CK. Deletion of 17p was present in 4 (16%) pts, but only 3 of 4 cases with 17p loss displayed TP53 mutation.

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Results:

Eighteen pts (TP53 wt) reseived 4 cycles of alternating of rituximab, bendamustine, cytarabine (R-BAC) and rituximab, high dose cytarabine 12 g/m2 (R-HA), followed by stem cell mobilization and ASCT. MRD was not detected in all 18 pts at the end of therapy. Eighteen pts achieved and remain in complete remission and 3 pts continue on treatment. The median follow-up time was 5 months after ASCT (range, 1-17 months). Pts with MCL, who have TP53 mutations, had a worse prognosis. Two pts with TP53 mutation in our study died for progression disease. Two pts, who underwent allo-HCT from non-relative HLA-matched donors, is a alive in CR, with the time of observation three and twenty-seven months.

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Summary/Conclusion:

The regimens R-BAC/R-HA was well tolerated with a manageable safety profile. Allogeneic hematopoietic cell transplantation is only curative treatment for MCL with TP53 gene mutation.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.