Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial.
Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial.
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DOI：
10.1186/s13045-016-0243-8
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发表时间：
2016-03-10
影响因子：
28.5
通讯作者：
Coiffier B
中科院分区：
文献类型：
--
作者：
Foss F;Horwitz S;Pro B;Prince HM;Sokol L;Balser B;Wolfson J;Coiffier B
复发性/难治性外周T细胞淋巴瘤（PTCL）患者实现持久缓解对当前治疗具有挑战性，并且关于最佳缓解为疾病稳定（SD）的患者继续治疗的潜在获益的数据很少。组蛋白去乙酰化酶抑制剂是一类新型的治疗T细胞恶性肿瘤的药物。根据一项关键性试验，罗米地辛被美国食品药品监督管理局批准用于治疗复发性/难治性PTCL，该试验显示客观缓解率为25%（33/130），包括15%的确认/未确认完全缓解，中位缓解持续时间为28个月。我们的目的是进一步研究罗米地辛在最佳缓解为SD的患者中的临床获益。对≥1种既往治疗复发/难治的PTCL患者在6个28天周期的第1、8和15天接受批准剂量14 mg/m2罗米地辛治疗;允许第6周期后SD或缓解的患者继续参加研究，直至进展。根据方案修订，接受≥12个周期治疗的患者可接受维持给药，每周期2次;在第24周期后，接受维持给药≥6个月的患者可进一步减少至每周期1次。在最佳缓解为SD的32例患者（25%）中，22例SD ≥90天（SD 90;第4周期缓解评估）。在第13周期开始的第1天和第15天接受14 mg/m2维持剂量的患者中，最长SD>3年。最佳缓解为SD 90或部分缓解的患者实现了相似的总体和无进展生存期。罗米地辛延长给药耐受性良好。我们得出结论，达到SD的患者可以考虑继续治疗，因为罗米地辛的临床获益可能超出客观缓解。NCT00426764
Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130), including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Of the 32 patients (25 %) with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment). The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. NCT00426764