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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.

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Related in: MedlinePlus

Incidence of grade ≥ 3 AEs by treatment cycle. Cycles in which no grade ≥ 3 AEs were reported are not included.
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Figure 5: Incidence of grade ≥ 3 AEs by treatment cycle. Cycles in which no grade ≥ 3 AEs were reported are not included.

Mentions: As previously reported, the most common AEs included gastrointestinal disturbances, hematologic abnormalities, asthenic conditions, and infections (all types pooled) [17]. Reported electrocardiogram (ECG) abnormalities were uncommon, with no concurrent symptoms of syncope or other cardiac AEs at the time of reported ECG abnormality and no clinically significant changes in QT intervals across treatment cycles were found [17]. The AE profile was similar across the 3 most common PTCL subtypes. Longer treatment duration did not affect the safety profile of romidepsin. Grade ≥ 3 AEs occurred with the highest incidence during cycles 1 to 2 (Figure 5). After cycle 18, ≤ 10 patients remained on treatment, and most grade ≥ 3 AEs reported were from 1 patient with grade ≥ 3 vomiting, cellulitis, deep vein thrombosis, and/or constipation in cycles 22, 24, 27, 31, and 32. In addition, one patient had grade ≥ 3 pyrexia in cycle 22 and one patient had grade ≥ 3 pneumonia in cycle 24.


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)

Incidence of grade ≥ 3 AEs by treatment cycle. Cycles in which no grade ≥ 3 AEs were reported are not included.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Incidence of grade ≥ 3 AEs by treatment cycle. Cycles in which no grade ≥ 3 AEs were reported are not included.
Mentions: As previously reported, the most common AEs included gastrointestinal disturbances, hematologic abnormalities, asthenic conditions, and infections (all types pooled) [17]. Reported electrocardiogram (ECG) abnormalities were uncommon, with no concurrent symptoms of syncope or other cardiac AEs at the time of reported ECG abnormality and no clinically significant changes in QT intervals across treatment cycles were found [17]. The AE profile was similar across the 3 most common PTCL subtypes. Longer treatment duration did not affect the safety profile of romidepsin. Grade ≥ 3 AEs occurred with the highest incidence during cycles 1 to 2 (Figure 5). After cycle 18, ≤ 10 patients remained on treatment, and most grade ≥ 3 AEs reported were from 1 patient with grade ≥ 3 vomiting, cellulitis, deep vein thrombosis, and/or constipation in cycles 22, 24, 27, 31, and 32. In addition, one patient had grade ≥ 3 pyrexia in cycle 22 and one patient had grade ≥ 3 pneumonia in cycle 24.

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