5-Azacitidine May Lead to Sustained Response in Peripheral T-Cell Lymphoma

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Patients with peripheral T-cell lymphomas have a median overall survival of approximately 6 months.
Patients with peripheral T-cell lymphomas have a median overall survival of approximately 6 months.

Patients with angioimmunoblastic T-cell lymphoma (AITL) may demonstrate a sustained response when treated with 5-azacitidine, according to a study published in Blood.

Prognosis for peripheral T-cell lymphomas such as AITL is poor, with a median overall survival of approximately 6 months. Of patients with AITL, 80% have mutations in TET2, 25% have mutations in DNMT3A, and 25% have mutations in IDH2; these genes are also mutated in myeloid neoplasms. Treatment of both patients with AITL and patients with myeloid neoplasms appears efficacious to a degree that directly correlates with mutations in these genes.

In this study, researchers retrospectively analyzed data from 12 patients (median age 70.5 years) with AITL who were treated with 5-azacitidine for concomitant myeloid neoplasm or as compassionate therapy in relapsing/refractory AITL; 5 patients (41%) had an associated myeloid neoplasm. Patients received 75 mg/m2 5-azacitidine daily, subcutaneously, for 7 consecutive days, every 28 days, for a median of 5.5 cycles. Half the patients received rituximab in addition to 5-azacitidine due to the presence of Epstein-Barr virus replication or B-blasts. Tumor samples were collected from the patients and sequenced to determine TET2, IDH2, DNMT3A, and RHOA status.

The patients tolerated the treatment well. No patients developed febrile neutropenia, and there were no treatment-related deaths or deaths due to myeloid neoplasm. Six patients (50%) showed a complete response and 3 patients (25%) showed a partial response, yielding an overall response rate of 75%.

The median progression-free survival was 15 months; the median overall survival was 21 months, with 5 patients showing sustained response and complete remission more than 23 months after treatment was initiated.

TET2, DNMT3A, RHOA, and IDH2 mutations were found in 58%, 33%, 41%, and 8% of patients, respectively. No relationship between number or presence of mutations and response to treatment was found.

All patients with an associated myeloid neoplasm responded to the treatment, and 4 of 7 patients without an associated myeloid neoplasm demonstrated a response, suggesting that success of the treatment is not limited only to patients with an associated myeloid disease.

The researchers concluded, “The mechanism of action of 5-azacitidine in AITL is not elucidated yet…. Several other questions remain unanswered [and] warrant a prospective study.”

Disclosure: Multiple authors declare affiliations with Celgene.

Reference

1. Lemonnier F, Dupuis J, Sujobert P, et al. Treatment with 5-Azacytidine Induces a Sustained Response in Patients with Angioimmunoblastic T-Cell Lymphoma [published online October 2, 2018]. Blood. doi: 10.1182/blood-2018-04-840538

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