Pralatrexate injection combined with oral leucovorin for mucositis management in PTCL/CTCL treatment: a multicenter phase 2 trial

Blood Neoplasia Pub Date : 2025-02-01 DOI:10.1016/j.bneo.2024.100055

Swaminathan P. Iyer , Shaker Dakhil , Michi M. Shinohara , Jasmine Zain , Mark Acosta , Francine Foss

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Abstract

Pralatrexate (Folotyn) is an antifolate indicated for the treatment of relapsed/refractory peripheral T-cell lymphoma (PTCL), and although durable clinical benefit has been demonstrated, oral and gastrointestinal mucositis and/or skin reactions are frequent toxicity complications associated with pralatrexate treatment. Leucovorin (d,l-folinic acid) administration has been used as a standard rescue for patients receiving high-dose methotrexate therapy and has recently been studied in patients with PTCL and cutaneous T-cell lymphoma receiving pralatrexate. We describe results from a multicenter, phase 2, single-arm, open-label trial, conducted with the primary objective of evaluating the effect of leucovorin in preventing or reducing the incidence of grade 2 or higher oral mucositis associated with pralatrexate treatment in cycle 1. Patients were administered pralatrexate, 30 mg/m² as an IV push, once weekly for 6 weeks in each cycle, followed by a week of rest (no treatment). Leucovorin 25 mg tablets were administered 3 times daily for 2 days (a total of 6 doses [150 mg cumulative weekly dose]), initiated 24 hours (±2 hours) after each pralatrexate dose. The evaluable population included 34 patients, with a mean age of 63.7 years and 60% males, of whom 2 (5.9%) developed grade 2 oral mucositis during the study period (P < .0001) and there were no reports of grade 3 or higher oral mucositis. Dose modifications, including omissions, delays, or reductions, due to oral mucositis were limited to 1 patient. Coadministration of leucovorin resulted in a significant reduction in mucositis and can be considered a prophylactic therapy in patients receiving pralatrexate treatment. This trial was registered at www.clinicaltrials.gov as #NCT02106650.

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普拉特雷酸注射液联合口服亚叶酸素治疗PTCL/CTCL治疗中的粘膜炎：一项多中心2期试验

摘要普拉特雷酸（Folotyn）是一种用于治疗复发/难治性外周t细胞淋巴瘤（PTCL）的抗叶酸药，尽管持久的临床疗效已被证明，但口腔和胃肠道粘膜炎和/或皮肤反应是普拉特雷酸治疗中常见的毒性并发症。亚叶酸素（d，l-亚叶酸）已被用作接受高剂量甲氨蝶呤治疗的患者的标准救援，最近在接受普拉蝶呤治疗的PTCL和皮肤t细胞淋巴瘤患者中进行了研究。我们描述了一项多中心、2期、单臂、开放标签试验的结果，该试验的主要目的是评估亚叶酸素在预防或减少第1周期普氨蝶呤治疗相关的2级或更高级别口腔黏膜炎发生率方面的作用。患者给予普拉特雷酸30 mg/m2静脉推注，每周1次，每个周期6周，然后休息1周（不治疗）。亚叶酸素25mg片剂，每日3次，连用2天（共6次[每周累计剂量150mg]），每次给药后24小时（±2小时）开始给药。可评估人群包括34例患者，平均年龄63.7岁，60%为男性，其中2例（5.9%）在研究期间发生2级口腔黏膜炎(P <；0.0001)，没有3级或更高级别口腔黏膜炎的报道。由于口腔黏膜炎导致的剂量调整，包括遗漏、延迟或减少，仅限于1例患者。联合使用亚叶酸可显著减少粘膜炎，可被认为是接受普拉蝶呤治疗的患者的一种预防性治疗。该试验在www.clinicaltrials.gov上注册为#NCT02106650。

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Blood Neoplasia

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