Witzig Thomas E, Tomblyn Michael B, Misleh Jamal G, Kio Ebenezer A, Sharkey Robert M, Wegener William A, Goldenberg David M
Mayo Clinic, Rochester, MN.
H. Lee Moffitt Cancer Center, Tampa, FL.
Haematologica. 2014 Nov;99(11):1738-45. doi: 10.3324/haematol.2014.112110. Epub 2014 Aug 22.
A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.
对非霍奇金淋巴瘤放射免疫疗法一直存在的一项批评是，使用未标记放射性的抗CD20抗体与放射性标记的抗CD20抗体一起使用。我们改为将放射免疫疗法与靶向不同B细胞抗原的免疫疗法相结合。我们评估了用抗CD22（90）Y-依帕珠单抗四乙酸盐联合抗CD20的维妥珠单抗治疗侵袭性淋巴瘤患者，这些患者至少有一次先前的标准治疗失败，但未接受过干细胞移植。18名患者（中位年龄73岁，先前治疗中位数为3次）接受200mg/m²维妥珠单抗，每周一次，共4周，在第3周和第4周给予计划剂量的（90）Y-依帕珠单抗四乙酸盐，在第2周给予（111）In-依帕珠单抗四乙酸盐用于成像和剂量测定。在给予放射免疫治疗剂量之前，维妥珠单抗有效地降低了血液中的B细胞水平。两种药物联合使用时，均未出现明显的免疫原性或药代动力学变化。（111）In成像显示肿瘤靶向，对正常器官的辐射剂量测定可接受。对于（90）Y-依帕珠单抗四乙酸盐，短暂性骨髓抑制是剂量限制性的，6mCi/m²（222MBq/m²）×2是最大耐受剂量。在17名可评估的患者中，根据2007年修订的治疗反应标准，9名（53%）患者有客观反应，包括3名（18%）完全缓解（其中2名在11个月和13个月后复发，1名在19个月时仍无临床疾病），6名（35%）部分缓解（1名在14个月后复发，5名在3至7个月后复发）。不同淋巴瘤组织学类型、不同（90）Y剂量水平以及预后不良预测风险的患者均出现反应，最重要的是，接受最大耐受剂量治疗的6名患者中有5名出现反应（其中2名获得持久完全缓解）。总之，在这个难以治疗的人群中，（90）Y-依帕珠单抗四乙酸盐和维妥珠单抗联合使用耐受性良好，具有令人鼓舞的治疗活性。
