Pagel John M, Spurgeon Stephen E, Byrd John C, Awan Farrukh T, Flinn Ian W, Lanasa Mark C, Eisenfeld Amy J, Stromatt Scott C, Gopal Ajay K
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
Br J Haematol. 2015 Jan;168(1):38-45. doi: 10.1111/bjh.13099. Epub 2014 Aug 22.
CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic. Patients with relapsed or refractory follicular non-Hodgkin lymphoma (FL), mantle cell lymphoma (MCL), or Waldenström's macroglobulinaemia (WM) received otlertuzumab at 20 mg/kg administered intravenously once a week for up to 8 weeks followed by 4 monthly doses. Sixteen patients were treated; median age was 62·5 years (range, 41-81), and median number of prior regimens was 4 (range, 1-7). Twelve patients were refractory to prior treatment, 5 were refractory to rituximab. The mean terminal half-life was 9·5 days. Lymph node reduction of ≥50% by computerized tomography scan measurements was seen in 3 of 12 patients, including one FL patient who had a partial response. One WM patient had a minor response. The most frequent adverse events were neutropenia, fatigue, nausea, thrombocytopenia, diarrhoea, and peripheral oedema; most were grade 1/2. Otlertuzumab treatment appears to have been well tolerated by the patients in this study. Clinical activity was observed in this small heterogeneous cohort of highly refractory, heavily pretreated B-cell non-Hodgkin lymphoma patients. These data suggest that further clinical investigation in non-Hodgkin lymphoma is warranted.
CD37是一种存在于正常和恶性B细胞表面的四跨膜蛋白。奥妥珠单抗(TRU-016)是一种新型的人源化抗CD37蛋白疗法。复发或难治性滤泡性非霍奇金淋巴瘤(FL)、套细胞淋巴瘤(MCL)或华氏巨球蛋白血症(WM)患者接受奥妥珠单抗治疗,剂量为20mg/kg,静脉注射,每周一次,共8周,随后每月给药4次。16例患者接受了治疗;中位年龄为62.5岁(范围41-81岁),既往治疗方案的中位数为4(范围1-7)。12例患者对既往治疗耐药,5例对利妥昔单抗耐药。平均终末半衰期为9.5天。12例患者中有3例经计算机断层扫描测量淋巴结缩小≥50%,其中1例FL患者有部分缓解。1例WM患者有轻微缓解。最常见的不良事件是中性粒细胞减少、疲劳、恶心、血小板减少、腹泻和外周水肿;大多数为1/2级。在本研究中,患者对奥妥珠单抗治疗的耐受性似乎良好。在这个高度难治性、经过大量预处理的B细胞非霍奇金淋巴瘤患者的小型异质性队列中观察到了临床活性。这些数据表明,有必要对非霍奇金淋巴瘤进行进一步的临床研究。