TORNA ALL’ELENCO

Focus on Patients with TP53 Disruption in the Fondazione Italiana Linfomi (FIL) MCL0208 Trial: Uniform Poor Outcome, Regardless of Baseline Predictors, MRD Status and Lenalidomide Maintenance in Haematologica

2020
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (26)Vedi tutti...

Alessandria B

Ferrero S

Zaccaria GM


et alii...

Abstract

Background: In the FIL MCL0208 phase III trial (NCT02354313), a 24 months maintenance with lenalidomide (LM) after autologous transplantation (ASCT) in 300 younger MCL patients (pts) resulted in better Progression Free Survival (PFS) vs. observation (OBS). Moreover, patients achieving minimal residual disease (MRD) negativity in bone marrow (BM) overall showed a better outcome. On the other hand, TP53 disruptions independently predicted dismal outcome. In this abstract we describe the specific clinical features and outcome characteristics of TP53 disrupted pts of our prospective series. Methods: TP53 disrupted pts were identified by NGS targeting resequencing and copy number variation analysis (on either BM sorted tumoral cells or FFPE lymph node). To identify prognostic factors(PFs) according to PFS, a univariate analysis was applied via Cox modeling via R (3.5.2). Survival analysis was performed using Kaplan-Meier model. Results: Overall, 241 pts had complete mutational data and were thus included in the present analysis: 39 (16%) showed a TP53 disruption. No statistically significant differences were registered at baseline between disrupted and wild type (WT) pts in terms of age, gender, stage, bulky disease or ECOG PS. In contrast, Ki-67 > 30% was more frequent in TP53 disrupted pts (54% vs. 24%,p=0.001), as well as blastoid histology (26% vs. 5%,p<0.001), abnormal LDH (62% vs. 42%,p<0.05) and high risk MIPI (23% vs. 11%, p=0.069). Of note, only 24/39 disrupted pts received ASCT vs. 177/202 WT (62% vs. 88%, p<0.001), as 7 TP53 pts progressed before ASCT, while 3 experienced early death and 5 unacceptable toxicity. No significant differences were recorded in terms of complete response (CR) at midterm (21% vs. 25%), however only 17/39 disrupted pts vs. 147/202 WT (44% vs. 73%, p<0.001) achieved CR before ASCT and 19/39 vs. 164/202 (49% vs. 81%, p<0.001) after ASCT. No differences were registered in terms of midterm/post-ASCT MRD negativization rates. Finall

Keywords

univariate analysis; survival analysis; risk assessment; remission; randomized controlled trial; prospective study; progression free survival; phase 3 clinical trial; minimal residual disease; male; major clinical study; lymph node; human; human tissue; histopathology; histology; gender; high risk patient; female; copy number variation; controlled study; conference abstract; clinical trial; clinical feature; cancer survival; cancer staging; cancer prognosis; cancer patient; bone marrow; autotransplantation; adult; protein p53; lenalidomide; endogenous compound; wild type;