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.
- T cell