Rapid and Durable Complete Remission of Refractory AITL with Azacitidine Treatment in Absence of TET2 Mutation or Concurrent MDS

Gareth Gregory, Michael J Dickinson, Costas Yannakou, Jonathan Wong, Piers A. Blombery, Greg Corboy, Lev Kats, Timothy Crozier, Beena Kumar, Miles Prince, Stephen S Opat, Jake Shortt

Research output: Contribution to journalLetterOtherpeer-review


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.1 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.2–4 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)].3,5 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.6–8

Herein, we describe the case of a rapid, durable and complete response to azacitidine in a patient with AITL previously refractory to 10 lines of therapy. Next generation sequencing studies performed on the patient's tumor did not detect mutations or copy number alteration in recurrently mutated genes of AITL including TET2, IDH2, RHOA and/or DNMT3A. In addition, the patient did not have a concomitant diagnosis of MDS or receive treatment for EBV reactivation. We posit that the therapeutic benefit of azacitidine in AITL is not dependent on the presence of high-frequency recurrent mutations of canonical DNA methylation regulators, or at the very least that therapeutic benefit may still be derived in the absence of such mutations. These findings warrant prioritization of prospective studies of HMAs for patients with AITL irrespective of the mutational profile or presence of concomitant MDS.

A 54-year old man was referred to our service in 2011 with a rapidly enlarging left inguinal nodal mass and B-symptoms. Lymph node biopsy confirmed a diagnosis of AITL (Fig. 1A) and staging investigations confirmed Ann-Arbor stage II disease. The blood and bone marrow examinations exhibited marked eosinophilia, but no evidence of lymphoma, dysplasia or monocytosis. From 2011 to 2013, his disease was refractory to nine lines of therapy (Table 1) with only transient partial responses achieved at best. He was then enrolled in a phase II clinical trial of panobinostat (NCT01658241), however, he did not achieve an objective response to this agent. By 2014, the patient had received 10 lines of failed therapies in which he had never achieved a complete remission.
Original languageEnglish
Article numbere187
Number of pages4
Issue number2
Publication statusPublished - Apr 2019


  • T cell
  • Azacitidine
  • angioimmunoblastic
  • TET2
  • Refractory
  • Lymphoma
  • Remission

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