Conference Coverage

HDAC/HMA combo shows ‘remarkable’ activity in PTCL



– A combination of 5-azacytidine and romidepsin showed promising activity in patients with peripheral T cell lymphomas, particularly angioimmunoblastic T-cell lymphoma (AITL) and primary cutaneous follicular helper T-cell lymphoma (PTCL-TFH), results of a phase 2 study showed.

Dr. Lorenzo Falchi, Columbia University Medical Center and New York Presbyterian Hospital, New York

Dr. Lorenzo Falchi

Of 16 patients with AITL or PTCL-TFH, 11 (69%) had a clinical response to the 5-azacytidine (AZA)/romidepsin combination, including 8 (50%) with complete responses (CRs), and 3 with partial responses (PRs), reported Lorenzo Falchi, MD, of Columbia University Medical Center and New York Presbyterian Hospital, New York, and colleagues.

“We show that the combination of oral AZA/romidepsin is remarkably active in patients with T-cell lymphomas. Clearly more patients with other subtypes are needed to better evaluate this combination,” Dr. Falchi said at the International Conference on Malignant Lymphoma.

The combination is intended to target epigenetic changes in PTCLs, which often bear mutations in TET2, DNMT3A, and IDH2. These mutations create global hypermethylation and cause transcriptional silencing of tumor suppressor genes, Dr. Falchi said.

Both histone deacetylase inhibitors such as romidepsin, and hypomethylating agents such as AZA have been shown to have single-agent activity against PTCL, and as previously reported at the 2018 T-cell Lymphoma Forum, the combination produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

Dr. Falchi presented the phase 2 results at 15-ICML. A total of 25 patients with newly diagnosed or relapsed/refractory PTCL were treated with AZA 300 mg daily on days 1-14 and romidepsin 14 mg/m2 on days 8, 15, and 22, every 35 days.

A total of 24 patients were evaluable for response. The ORR – the primary endpoint – was achieved in 14 patients (58%), and included 10 CRs and 4 PRs. Three additional patients had stable disease, and six patients experienced disease progression (response data for one patient was not complete at the time of the presentation).

In total, 11 of 16 patients with AITL/PTCL-TFH had responses, compared with 3 of 8 patients with other histologies.

A secondary analysis of 16 patients with information on mutational status showed that 10 of 12 patients with TET2 mutations (83%) had responses, including 8 CRs and 2 PRs. Two additional patients with TET2 mutations had disease progression. In contrast, among four patients without TET2 mutations, one had a CR, one a PR, and two had disease progression.

Of the 10 patients overall with CRs, 5 patients were receiving the combination in the first line, and 5 patients were receiving it for relapsed/refractory disease.

Median PFS among all patients was 8.7 months. The median overall survival has not been reached. Among patients with the AITL or PTCL-TFH subtypes, median PFS was 8.7 months, compared with 2.3 months for patients with other histologies.

The most frequent hematologic grade 3 or 4 adverse events were thrombocytopenia and neutropenia. The most frequent nonhematologic grade 3 or 4 events included lung infection and febrile neutropenia. Common grade 1 or 2 toxicities included anemia, diarrhea, fatigue, nausea, and vomiting. No patients discontinued therapy because of adverse events.

Dr. Falchi noted that a phase 1 trial evaluating the immune checkpoint inhibitor durvalumab (Imfinzi) with AZA or romidepsin alone or in combination, or pralatrexate and romidepsin, is currently recruiting.

Dr. Falchi reported having no financial disclosures. Other investigators reported funding from Celgene, which supported the study.

SOURCE: Falchi L et al. 15-ICML, Abstract 129.

Next Article: