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

Abstract

Background: Romidepsin 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.

Methods: Patients 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.

Results: The 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.

Conclusions: Treatment 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 registration: ClinicalTrials.gov NCT00426764.

Figure 1

Durations of response for the 3 most common subtypes of PTCL in patients who achieved a response (CR or PR). ◦ Indicates a censored patient.

Figure 2

Durations of response for patients who achieved CR/CRu on romidepsin (investigator assessed; n = 21). Only investigators assessed DOR for prior therapy (for patients with PR or CR on prior therapy). Arrows indicate that the patient was censored while in response. * Indicates that the patient received combination chemotherapy as the last prior therapy. NR indicates that the response to prior therapy was not reported.

Figure 3

Durations of response for patients who achieved CR/CRu on romidepsin (IRC). The vertical line separates the 10 patients with long-term responses (duration ≥ 12 months). Of the 2 patients that received stem cell transplant after romidepsin, type of transplant was autologous for 1 patient, and not reported for 1 patient.

Figure 4

Survival (PFS, OS) by quality of response to romidepsin.

Figure 5

Incidence of grade ≥ 3 AEs by treatment cycle. Cycles in which no grade ≥ 3 AEs were reported are not included.