From the Journals

AITL responds to 5-azacytidine in small series



Older patients with refractory angioimmunoblastic T cell lymphoma (AITL) appear to respond well to treatment with 5-azacytidine, regardless of mutations.

Francois Lemonnier, MD, of Henri Mondor University Hospitals in Créteil, France, and his colleagues, reported on a retrospective series of 12 AITL patients who received 5-azacytidine for concomitant myeloid neoplasm or as compassionate therapy for relapsed or refractory AITL. The findings were published in Blood.

Patients were given 5-azacytidine subcutaneously at a dose of 75 mg/m2 daily for 7 consecutive days. The treatment was given every 28 days until progression or unacceptable toxicity for a median of 5.5 cycles. Along with 5-azacytidine, half of the patients received rituximab due to the presence of EBV replication or EBV B-blasts in the lymph node biopsy.

The patients were assessed via CT scan and responses were evaluated by investigators following the Cheson criteria.

This was a heavily pretreated patient population. The median age was 70 years and 11 of the patients had relapsed or refractory disease and had received a median of two lines of therapy. There was only one treatment-naive patient in the series.

Treatment with 5-azacytidine produced an overall response rate of 75%, with six patients achieving a complete response and three patients achieving a partial response. The median progression-free survival was 15 months and median overall survival was 21 months at a median follow-up of 27 months.

The researchers noted that some elderly patients with poor performance status achieved a sustained response after treatment with an acceptable tolerance.

Treatment was well tolerated overall. There were no treatment-related deaths and no patients developed neutropenia. Three patients required transfusion and another had grade 3 diarrhea.

The researchers also performed molecular studies using targeted deep sequencing. They detected TET2 mutations in all 12 patients, with seven patients having two mutations. Four patients had DNMT3A mutations, five patients had RHOA mutations, and four patients had p.G17V substitution. One patient had an IDH2R172 mutation.

Since all patients had a TET2 mutation, the researchers were unable to assess its impact on treatment response. However, they saw no association between the number of TET2 mutations and treatment response, or mutations in DNMT3A, IDH2, and RHOA and treatment response.

The study was funded by a grant from the Leukemia & Lymphoma Society. Three of the coauthors received honoraria from Celgene.

SOURCE: Lemonnier F et al. Blood. 2018 Oct 2. doi: 10.1182/blood-2018-04-840538.

Next Article: