Frankel Arthur E, Woo Jung H, Ahn Chul, Foss Francine M, Duvic Madeleine, Neville Paul H, Neville David M
University of Texas Southwestern Medical Center, Dallas, TX
Baylor Scott & White Health, Temple, TX.
Haematologica. 2015 Jun;100(6):794-800. doi: 10.3324/haematol.2015.123711. Epub 2015 Mar 20.
Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 - 11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208.
Resimmune是一种第二代重组免疫毒素，由白喉毒素的催化和转位结构域与两个与CD3ε细胞外结构域反应的单链抗体片段融合而成。在一项患者间剂量递增试验中，我们在15分钟内给30例患者静脉输注2.5 - 11.25μg/kg的Resimmune（25例皮肤T细胞淋巴瘤患者、3例外周T细胞淋巴瘤患者、1例T细胞大颗粒淋巴细胞白血病患者和1例T细胞原淋巴细胞白血病患者）。最常见的不良事件是发热、寒战、低血压、水肿、低白蛋白血症、低磷血症和转氨酶血症。在25例皮肤T细胞淋巴瘤患者中，有9例有反应，反应率为36%（95%CI，18%-57%），包括4例完全缓解（16%，95%CI，5%-36%）。完全缓解的持续时间分别为72+、72+、60+和38+个月。有5例部分缓解，持续时间为3、3、3+、6+和14个月。在17例改良皮肤加权评估工具评分<50的患者中、17例IB/IIB期患者以及11例评分<50且为IB/IIB期的患者中，分别有9例（53%）、8例（47%）和8例（73%）有反应。有必要对肿瘤负荷低的IB-IIB期皮肤T细胞淋巴瘤患者进一步研究Resimmune。该试验已在clinicaltrials.gov注册，编号为#NCT00611208。
