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

Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan Iyer S, Shustov A, Nielsen T, Nichols J, Wolfson J, Balser B, Horwitz S - J Hematol Oncol (2014)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hospices Civils de Lyon, Lyon, France. bertrand.coiffier@univ-lyon1.fr.

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.

Show MeSH

Related in: MedlinePlus

Durations of response for the 3 most common subtypes of PTCL in patients who achieved a response (CR or PR). ◦ Indicates a censored patient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016573&req=5

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.

Mentions: Most responses were noted at the first response assessment (2 months), and the median time to response as assessed by the IRC was 1.8 months (range, 1.4-5.3 months). The median DOR for all patients who achieved a response by IRC (n = 33) was 28 months (range, < 1-48+) and had not been reached (range, < 1-48+) for those who achieved CR/CRu (n = 19). One patient with a reported DOR < 1 month discontinued treatment to receive SCT after the first response assessment of CR. Of the 19 patients who achieved CR/CRu, 53% had a DOR ≥ 12 months and 32% had a DOR ≥ 24 months. Responses were durable across the 3 most common PTCL subtypes (Figure 1), and no statistically significant differences in DOR were observed. For patients with progressive disease (PD) to their last prior therapy (n = 49), the median DOR on romidepsin had not yet been reached for all patients who achieved a response (n = 14) or for patients wxho achieved CR/CRu (n = 9).


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

Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan Iyer S, Shustov A, Nielsen T, Nichols J, Wolfson J, Balser B, Horwitz S - J Hematol Oncol (2014)

Durations of response for the 3 most common subtypes of PTCL in patients who achieved a response (CR or PR). ◦ Indicates a censored patient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016573&req=5

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.
Mentions: Most responses were noted at the first response assessment (2 months), and the median time to response as assessed by the IRC was 1.8 months (range, 1.4-5.3 months). The median DOR for all patients who achieved a response by IRC (n = 33) was 28 months (range, < 1-48+) and had not been reached (range, < 1-48+) for those who achieved CR/CRu (n = 19). One patient with a reported DOR < 1 month discontinued treatment to receive SCT after the first response assessment of CR. Of the 19 patients who achieved CR/CRu, 53% had a DOR ≥ 12 months and 32% had a DOR ≥ 24 months. Responses were durable across the 3 most common PTCL subtypes (Figure 1), and no statistically significant differences in DOR were observed. For patients with progressive disease (PD) to their last prior therapy (n = 49), the median DOR on romidepsin had not yet been reached for all patients who achieved a response (n = 14) or for patients wxho achieved CR/CRu (n = 9).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hospices Civils de Lyon, Lyon, France. bertrand.coiffier@univ-lyon1.fr.

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.

Show MeSH
Related in: MedlinePlus