Presence of multiple recurrent mutations revealed by targeted NGS confers poor trial outcome of relapsed/refractory CLL
Menée à l'aide de technologies de séquençage à haut débit sur 114 patients atteints d'une leucémie lymphocytaire chronique récidivante/réfractaire, cette étude franco-britannique identifie des mutations dans un panel de 9 gènes en association avec un pronostic défavorable
While TP53, NOTCH1 and SF3B1 mutations may impair prognosis of patients with CLL receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in prospective trials was screened using targeted NGS of TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3 and MYD88 genes. We performed clustering according to both number and combinations of recurrent gene mutations. The number of genes affected by mutation was ≥ 2, 1 and 0 in 43 (38%), 49 (43%) and 22 (19%) respectively. Recurrent combinations of ≥ 2 mutations of the following genes: TP53, SF3B1 and ATM were found in 22 (19%) patients. This 'multiple-hit' profile was associated with a median PFS of 12 months compared to 22.5 months in the remaining patients (P = .003). Concurrent gene mutations are frequent in patients with relapsed/refractory CLL and are associated with worse outcome.