Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses

Abstract

BackgroundRomidepsin is a structurally unique, potent, bicyclic class 1 selective histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received ≥ 1 prior systemic therapy and patients with peripheral T-cell lymphoma (PTCL) who have received ≥ 1 prior therapy. Approval for PTCL was based on results (n = 130; median follow-up, 13.4 months) from the pivotal study of romidepsin for the treatment of relapsed/refractory PTCL. The objective is to present updated data (median follow-up, 22.3 months) and to characterize patients who achieved long-term responses (≥ 12 months) to romidepsin.MethodsPatients with PTCL who relapsed from or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; patients with response or stable disease could continue romidepsin beyond 6 cycles. The primary endpoint was rate of confirmed/unconfirmed complete response (CR/CRu) determined by an Independent Review Committee. Secondary endpoints included objective response rate (ORR) and duration of response (DOR). For patients who achieved CR/CRu, baseline characteristics by DOR (≥ 12 vs < 12 months) were examined.ResultsThe ORR to romidepsin was 25%, including 15% with CR/CRu. The median DOR for all responders was 28 months (range, < 1-48+) and was not reached for those who achieved CR/CRu. Patients with lack of response or transient response to prior therapy achieved durable responses with romidepsin. Of the 19 patients who achieved CR/CRu, 10 had long-term (≥ 12 months) responses; none of the baseline characteristics examined—including heavy pretreatment, response to prior therapy, or advanced disease—precluded long-term responses to romidepsin. With a median progression-free survival of 29 months, patients who achieved CR/CRu for ≥ 12 months had significantly longer survival vs those with CR/CRu for < 12 months or < CR/CRu. Extended treatment and longer follow-up did not affect the reported safety profile of romidepsin.ConclusionsTreatment with romidepsin leads to highly durable responses in a subset of patients with relapsed/refractory PTCL, with responses ongoing as long as 48 months.Trial registrationNCT00426764

Romidepsin induces durable responses in patients with relapsed or refractory angioimmunoblastic T‐cell lymphoma

“…The AE profile for patients with AITL was consistent with the known profile for romidepsin in patients with all subtypes of PTCL 11, 12, 13. The most common grade ≥3 AEs were thrombocytopenia (30%, all drug‐related), neutropenia (22%, all drug‐related), infections (all types pooled; 22%, 4% drug‐related) and anemia (15%, 7% drug‐related).…”

Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence

“…histone deacetylases [HDAC]), proteins with enzymatic activity that either add or remove post-translational modifications respectively to histone proteins. Vorinostat is the first HDAC inhibitor approved for treatment of relapsed cutaneous T-cell lymphoma [Duvic et al 2007;Grant et al 2007;Mann et al 2007] and along with other HDAC inhibitors such as romidepsin and panobinostat, is in clinical trials for other types of lymphoma and for multiple myeloma [Dimopoulos et al 2013;Coiffier et al 2014;Straus et al 2014].…”

Effect of histone deacetylase inhibitor romidepsin on thein vitrogrowth of foetal fibroblast cells and early development of porcine-cloned embryos

“…Previous studies have confirmed that FK228 is a novel HDACi that could effectively inhibit the proliferation of tumour cells (Coiffier et al 2014;Mummaneni & Shord 2014;Wei et al 2014) and suffer more cytotoxicity in cancer cells than normal cells (Kasman et al 2007;Emanuele et al 2008). This study showed that FK228 treatment has a concentration-and time-dependent effect on the morphology and growth of porcine foetal fibroblast cells; and these findings are consistent with the results reported previously (Savickiene et al 2006;Hoshino et al 2008).…”