Genomic mutation profile in progressive chronic lymphocytic leukemia patients prior to first-line chemoimmunotherapy with FCR and rituximab maintenance (REM).

Julia González-Rincón,Sagrario Gómez,Miguel Fernández-Zarzoso,Javier De La Serna,Lucrecia Yáñez,Raúl Córdoba,Raquel Paz-Arias,M Ángeles Ruíz-Guinaldo,Valle Recasens,Sara Nova-Gurumeta,José A García-Marco,Jaime Pérez De Oteyza,Eduardo Anguita,Marcos González,Rosa Collado,Nuria Pérez-Sanz,Miguel Alcoceba,Belén Fernández-Cuevas,Belén Navarro‐Matilla ,Eva González‐Barca ,M.c Fernández ,María Angeles Andreu ,Madolores García-Malo ,Javier López‐Jiménez ,Guillermo Debén ,Francisco Javier Peñalver ,Margarita Sánchez‐Beato ,José Antonio García-Vela ,Ernesto Pérez‐Persona

doi:10.1371/journal.pone.0257353

Abstract

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment.

Highlights

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes that defines two subgroups characterized by different clinical outcomes
The standard treatment of choice as first-line therapy for young physically fit patients with CLL is the combination of chemoimmunotherapy (CIT) with fludarabine, cyclophosphamide and rituximab (FCR)
Long-term results from three studies [8,9,10] have demonstrated a long-duration progression-free survival (PFS) and overall survival (OS) of nearly 12 years in the subset of patients with mutated IGHV and an absence of adverse genetic features (11q deletion [del(11)] or 17p deletion [del(17)]/TP53 mutation) after treatment with front-line FCR

Summary

Introduction

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. We have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in a prospectively selected group of patients with CLL with active progressive disease who require treatment.

Results

Conclusion