Rapid and durable complete remission of refractory AITL with azacitidine treatment in absence of TET2 mutation or concurrent MDS.

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a rare disease entity associated with poor prognosis and no improvement in overall survival over the last 20 years. The genomic landscape of AITL has revealed frequent mutation of epigenetic modifiers TET2 (76%), DNMT3A (33%) and IDH2 (20%), genetic mutations that may be predictive of response to hypomethylating agents (HMA) in myelodysplastic syndromes. Genomic profiling has also demonstrated TET2 mutations to be present in both malignant and non-malignant hematopoietic cells of affected individuals, suggesting loss of TET2 to be the initiating mutation, following which secondary mutations direct the lineage phenotype of subsequent malignancy [eg, secondary RHOA mutations in AITL versus myeloid-lineage associated mutations in genes such as RAS leading to myelodysplasia (MDS) / chronic myelomonocytic leukemia (CMML)]. The potential efficacy of HMAs in the treatment of AITL has emerged from the observation of regressing lymphadenopathy in patients treated for their concomitant MDS, however, such AITL responses may have been confounded by frequent concurrent rituximab administration for Epstein-Barr virus (EBV)-reactivation which is characteristic of this disease.