Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-Cell malignancies
Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-Cell malignancies
复制标题
DOI：
10.1200/jco.2005.11.437
复制
发表时间：
2005-09-20
影响因子：
45.3
通讯作者：
Pastan, I
中科院分区：
文献类型：
--
作者：
Kreitman, RJ;Squires, DR;Pastan, I
目的：进行重组免疫毒素 BL22（一种与截短假单胞菌外毒素融合的抗 CD22 Fv 片段）的 I 期试验。患者和方法：46 名经过预处理的 CD22+ 非霍奇金淋巴瘤 (NHL；n = 4)、慢性淋巴细胞白血病 (CLL；n = 11) 和毛细胞患者 白血病（HCL；n = 31）接受 265 个周期，每隔一天 3 至 50 μg/Kg x 3 剂量。结果：BL22 在 HCL 中具有活性，31 名患者中有 19 例完全缓解（CR；61%）和 6 例部分缓解（PR；19%）。在 19 例 CR 中，11 例在 1 个周期后实现，8 例在 2 至 14 个周期后实现。所有 25 名反应者在一个周期内均获得临床获益。在≥ 40 μg/Kg 每隔一天 x 3 剂量入组的患者中，CR 率为 86%，在较低剂量下为 41% (P = .011)。 CR 的中位持续时间为 36 个月（范围为 5 至 66 个月），8 名患者在 45 个月时仍处于 CR（范围为 29 至 66 个月）。 CLL 中出现较低但显着的活动。 46 名患者（均为 HCL）中，有 11 名（24%）出现中和抗体。在第 1 周期期间，一名 NHL 患者和在第 2 或第 3 周期期间，4 名 HCL 患者观察到需要血浆置换的可逆性溶血性尿毒症综合征。第 1 周期评估的最大耐受剂量 (MTD) 为 40 μg/Kg IV。 QOD x 3。每隔一天 30 至 50 μg/Kg x 3 最常见的毒性包括低白蛋白血症、转氨酶升高、疲劳和水肿。结论：BL22 在 HCL 中具有良好的耐受性和高效性，即使在一个周期后也是如此。 II 期测试正在进行中，以确定一个周期的疗效，并研究需要额外周期以获得最佳反应时的安全性。
Purpose: To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin.Patients and Methods: Forty-six pretreated patients with CD22+ non-Hodgkin's lymphoma (NHL; n = 4), chronic lymphocytic leukemia (CLL; n = 11), and hairy cell leukemia (HCL; n = 31) received 265 cycles at 3 to 50 mu g/Kg every other day x 3 doses.Results: BL22 was active in HCL, with 19 complete remissions (CRs; 61 %) and six partial responses (PRs; 19%) in 31 patients. Of 19 CRs, 11 were achieved after one cycle and eight after two to 14 cycles. All 25 responders benefited clinically with one cycle. The CR rate was 86% in patients enrolled at >= 40 mu g/Kg every other day x 3, and 41 % at lower doses (P = .011). The median duration for CR was 36 months (range, 5 to 66 months), and eight patients remain in CR at 45 months (range, 29 to 66 months). Lower but significant activity occurred in CLL. Neutralizing antibodies occurred in 11 (24%) of 46 patients (all HCL). A reversible hemolytic uremic syndrome requiring plasmapheresis was observed in one patient with NHL during cycle 1 and in four patients with HCL during cycle 2 or 3. The maximum-tolerated dose (MTD) evaluated at cycle 1 was 40 mu g/Kg IV. QOD x 3. The most common toxicities at 30 to 50 mu g/Kg every other day x 3 included hypoalbuminemia, transaminase elevations, fatigue, and edema.Conclusion: BL22 was well tolerated and highly effective in HCL, even after one cycle. Phase II testing is underway to define the efficacy with one cycle and to study safety when additional cycles are needed for optimal response.