Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study

Dupuis, Jehan; Morschhauser, Franck; Ghesquières, Hervé; Tilly, Hervé; Casasnovas, Olivier; Thiéblemont, Catherine; Ribrag, Vincent; Bossard, Céline; Bras, Fabien Le; Bachy, Emmanuel; Hivert, Bénédicte; Nicolas‐Virelizier, Emmanuelle; Jardin, Fabrice; Bastie, Jean-Noël; Amorim, Sandy; Lazarovici, Julien; Martin, Antoine; Coiffier, Bertrand

doi:10.1016/s2352-3026(15)00023-x

Cited by 102 publications

(79 citation statements)

References 15 publications

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“…Current studies are evaluating the combination of these newly approved agents with chemotherapeutic regimens. Preliminary results from a phase 1B study of romidepsin in combination with CHOP for the first-line treatment of patients with PTCL (14 evaluable patients) demonstrated an ORR of 78%, including 57% CR [27], and a phase 2 extension study is ongoing. A separate phase 3 study of romidepsin + CHOP vs CHOP alone in frontline PTCL is also ongoing [28].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…[78] Dose-limiting toxicities (DLTs) in phase Ib (n ¼ 18) included syncope, neutropenia, pulmonary edema, vomiting, hyponatremia, and hypophosphatemia. Most patients had grade 3 hematologic AEs, and the most common (all-grade) nonhematologic AEs reported were gastrointestinal, respiratory, or general conditions.…”

Section: Combinations With Chemotherapy Regimensmentioning

confidence: 99%

“…At the median follow-up of 30 months, estimated PFS and OS were 41% and 71%, respectively. [78] A separate phase III study of CHOP vs romidepsin þ CHOP in newly diagnosed PTCL is ongoing. [79] A phase I study of vorinostat þ CHOP in newly diagnosed PTCL (N ¼ 14) was also conducted.…”

Section: Combinations With Chemotherapy Regimensmentioning

confidence: 99%

Targeting histone deacetylases in T-cell lymphoma

Moskowitz

Horwitz

2016

Leukemia & Lymphoma

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“…The latter prompted trials combining romidepsin with alkylating agents in the hope of generating an additive cytotoxic effect. In PTCL, romidepsin in combination with both ifosfamide, carboplatin, and etoposide (ICE) salvage regimen in the relapse setting [10] and with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) regimen in previously untreated patients, had superior efficacy to single-agent romidepsin, yet with much higher toxicities, making these combinations an option for a very selected fit patient population [11]. Bendamustine is a unique cytotoxic drug, containing both an alkylating moiety and a purine-like benzimidazole ring.…”

Section: Introductionmentioning

confidence: 99%

Romidepsin-Bendamustine Combination for Relapsed/Refractory T Cell Lymphoma

et al. 2019

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Background: The treatment of relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL) is limited to a few agents. Romidepsin, a histone deacetylase inhibitor, was approved for PTCL treatment as a single agent in the R/R setting, yet with partial efficacy. Several attempts to combine romidepsin with other chemotherapy regimens have been reported, however, with significant toxicity. Objectives: To study the romidepsin-bendamustine combination in PTCL in an attempt to maximize efficacy while minimizing toxicity. Methods: We report on a series of 7 heavily pretreated PTCL patients (2–5 previous lines of therapy) treated with a romidepsin-bendamustine combination. Results: Four patients were not previously exposed to either drug. Of these, 2 achieved complete remission. Interestingly, 1 patient continued treatment with a prolonged progression-free survival of more than 4 years. Toxicity was minimal and no treatment-related deaths or discontinuation were noted. Significant nausea and vomiting were reported in over 50% of patients. Hematological toxicity was mild and lower than that reported for other romidepsin-chemotherapy combinations and was correlated with bone marrow involvement by lymphoma. Conclusions: Although reporting a small number of patients, our data suggest that the combination of romidepsin and bendamustine may be a feasible therapeutic option in R/R PTCL patients and merits further study.

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Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study

Cited by 102 publications

References 15 publications

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

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

Targeting histone deacetylases in T-cell lymphoma

Romidepsin-Bendamustine Combination for Relapsed/Refractory T Cell Lymphoma

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