Azacitidine and Romidepsin Combination Shows High Activity in Peripheral T-Cell Lymphoma

A combination regimen consisting of oral azacitidine and romidepsin was highly active in patients with peripheral T-cell lymphoma (PTCL), particularly in previously untreated patients and those with the T-follicular helper (TFH) cell phenotype, according to a study published in Blood.

The multicenter phase II study, led by Lorenzo Falchi, MD, of Columbia University Irving Medical Center, assessed the overall response rate (ORR) of the azacitidine and romidepsin combination in 25 adults with treatment-naïve or relapsed/refractory PTCL.

Treatment consisted of azacitidine 300 mg daily on days 1 through 14 and romidepsin 14 mg/m2 on days 8, 15, and 22, in 5-week cycles. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent.

In addition to assessing the ORR to treatment, Dr. Falchi and colleagues performed targeted next-generation sequencing (NGS) on tumor samples to correlate mutational profiles and response. Secondary objectives of the study included progression-free survival (PFS), duration of response (DOR), overall survival (OS), and identification of potential biomarkers of response.

Median age among the entire cohort was 63 years (range = 42-88). In total, 14 patients had relapsed/refractory disease and 11 had previously untreated disease. In the relapsed/refractory group, the median number of prior therapies was 2 (range = 1-6).

Two patients were not evaluable for response: one due to a concurrent malignancy, and one due to fatal sepsis from autoimmune neutropenia, both of which occurred before completing two cycles of therapy.

Among the 23 evaluable patients, the ORR (primary endpoint) was 61%, which included a complete response (CR) rate of 48%. Dr. Falchi and coauthors reported that responses appeared to be higher in the 10 patients with treatment-naïve disease:

  • treatment-naïve: ORR of 70% and CR rate of 50%
  • relapsed/refractory: ORR of 54% and CR rate of 38%

In addition, patients with the TFH phenotype had high ORR and CR rates (80% and 67%, respectively). There were no differences observed among the subset of patients with non-TFH histology in regard to response rates.

At the median follow up of 13.5 months, median PFS was 8.0 months in the entire population. In patients with TFH cell phenotype and those with other PTCL subtypes, the median PFS was 8.9 and 2.3 months, respectively (hazard ratio [HR] = 0.3; p=0.05).

Responses were considered generally durable, as reflected by a median DOR of 20.3 months, the authors reported. The DOR lasted longer in treatment-naïve patients (DOR = not reached) compared with patients with relapsed/refractory disease (DOR=13.5 months), but this difference did not reach statistical significance (HR=0.5; p=0.62).

The median OS was not reached in the overall study population, but the investigators noted that the median OS was significantly longer for patients with TFH histology compared with those with other subtypes (not reached vs. 9.4 months; HR=0.2; p=0.03). In addition, the median OS was not reached in treatment-naïve patients, whereas patients with relapsed/refractory disease had a median OS of 20.6 months.

“To our knowledge, this is the largest report of molecularly annotated PTCL patients treated with epigenetic modifiers.”

—Lorenzo Falchi, MD

“Recognizing the small numbers, the potentially higher response rate and longer median PFS among patients with TFH relative to those with other PTCL subtypes suggests that this histology may be more vulnerable to epigenetic modifiers,” the authors wrote.

The most frequently reported grade 3 or 4 adverse events in this study were:

  • thrombocytopenia (48%)
  • neutropenia (40%)
  • lymphopenia (32%)
  • anemia (16%)

“To our knowledge, this is the largest report of molecularly annotated PTCL patients treated with epigenetic modifiers and the first to address the question of whether mutations in the epigenome predict sensitivity to epigenetically predicated therapies,” the authors concluded. “No clear molecular biomarker has emerged as being predictive of response, though clearly more research is needed to validate gene panels of interest.”

Limitations of this study included the small number of patients in the final sample, the heterogeneity of patients in regard to histology and treatment history, and the short follow-up duration. The investigators also noted that the study was limited by the use of different NGS platforms in the analysis of mutations.

Study authors reported relationships with Celgene, which was a collaborator on this trial.


Falchi L, Ma H, Klein S, et al. Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study. 2020 November 10. Blood. [Epub ahead of print]