聚乙二醇干扰素α-2b治疗BCR-ABL阴性骨髓增殖性疾病：一项2期研究的最终结果

PEG-IFN-alpha-2b therapy in BCR-ABL-negative myeloproliferative disorders: final result of a phase 2 study.

作者信息

Jabbour Elias, Kantarjian Hagop, Cortes Jorge, Thomas Deborah, Garcia-Manero Guillermo, Ferrajoli Alessandra, Faderl Stefan, Richie Mary Ann, Beran Miloslav, Giles Francis, Verstovsek Srdan

机构信息

Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Cancer. 2007 Nov 1;110(9):2012-8. doi: 10.1002/cncr.23018.

DOI:10.1002/cncr.23018

PMID:17849460

Abstract

BACKGROUND

Interferon-alpha (IFN-alpha) has shown significant activity in the treatment of BCR-ABL-negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-IFN-alpha-2b is a pegylated IFN-alpha-2b with a significant advantage over nonpegylated form in that it is administered once a week.

METHODS

Thirty-eight patients with BCR-ABL-negative MPDs were treated with PEG-IFN-alpha-2b, given subcutaneously weekly, at the starting dose of 3 microg/kg/wk for the first 14 patients and then 2 microg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy.

RESULTS

Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR-ABL-negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3-4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months.

CONCLUSIONS

PEG-IFN-alpha-2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR-ABL-negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG-IFN-alpha-2b therapy are similar to those obtained with conventional IFN-alpha, thus limiting the duration of therapy.

摘要

背景

α干扰素（IFN-α）在治疗BCR-ABL阴性骨髓增殖性疾病（MPD），尤其是原发性血小板增多症（ET）和真性红细胞增多症（PV）方面显示出显著活性。聚乙二醇化干扰素α-2b（PEG-IFN-α-2b）是一种聚乙二醇化的IFN-α-2b，与非聚乙二醇化形式相比具有显著优势，即每周给药一次。

方法

38例BCR-ABL阴性MPD患者接受PEG-IFN-α-2b治疗，每周皮下注射，前14例患者起始剂量为3μg/kg/周，随后24例患者为2μg/kg/周，只要患者从治疗中获益就持续治疗。

结果

中位年龄为54岁。患者诊断为：13例（34%）ET；11例（29%）原发性骨髓纤维化（PMF）；5例（13%）BCR-ABL阴性慢性髓性白血病（CML）；4例（10.5%）高嗜酸性粒细胞综合征（HES）；4例（10.5%）PV；1例（3%）未分类的骨髓增殖性疾病（uMPD）。记录的3-4级毒性反应与疲劳、骨髓抑制和肌肉骨骼疼痛有关。10例（26%）患者因毒性反应停止治疗。13例（34%）患者达到完全缓解，4例（11%）患者达到部分缓解。仅1例PMF患者有反应。中位反应时间为5个月。中位缓解持续时间为20个月。3例患者有持续反应超过24个月。