PO.CL09.02 · 临床研究
慢性髓性白血病患者使用ponatinib、bosutinib和asciminib情况下皮肤不良反应的特征
Characterization of adverse cutaneous effects in the setting of ponatinib, bosutinib, andasciminib for chronic myeloid leukemia patients
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
BCR-ABL酪氨酸激酶抑制剂（TKI）用于治疗慢性髓性白血病（CML），包括第二代和第三代药物：ponatinib、bosutinib和asciminib。虽然第一代TKI（如imatinib）的皮肤不良事件（cAE）已有充分记录，但涉及较新药物的真实世界报告仍然有限且描述不足。因此，我们旨在表征接受ponatinib、bosutinib或asciminib治疗的CML患者cAE的范围。
我们对Mass General Brigham的Research Patient Data Registry从1979年至2024年的资料进行了回顾性病历审查。我们排除了无CML或未使用相关药物的患者。291例患者符合纳入标准，其中92例（32.3%）接受ponatinib，182例（62.5%）接受bosutinib，111例（38.1%）接受asciminib。37例（12.7%）患者出现有记录的cAE，其中1例患者出现2种不同的cAE。共有38起独立的cAE，包括皮疹（cAE=38）、瘙痒（cAE=20）、皮肤干燥（cAE=5）、色素沉着过度（cAE=2）和鳞状细胞癌（SCC）（cAE=1）。所有药物均可导致痤疮样疹和斑丘疹或丘疹样疹。ponatinib还诱发毛发红糠疹样、毛周角化病样、瘀点样和鱼鳞病样疹。ponatinib和bosutinib出现光敏性皮疹，而bosutinib和asciminib出现脓疱疹、斑块和湿疹样疹。cAE采用外用糖皮质激素（cAE=14）、润肤剂（cAE=10）和抗组胺药（cAE=9）治疗；17起事件中TKI剂量被暂停或停用。
cAE的中位持续时间从asciminib的35天到bosutinib的91.5天不等。60.5%的事件在用药开始后90天内出现。没有患者因cAE需要住院；大多数为1级严重程度（57.2%）。女性性别与cAE发生之间存在显著关联（OR 3.30，p=0.003），但与年龄、种族、族裔、既往CML治疗和初始剂量无关联。
我们详细描述了ponatinib、bosutinib和asciminib发生cAE的真实世界表现，观察到的发生率分别为16.3%、8.8%和6.3%。女性风险显著增加与既往文献一致，可能由于体型、用药依从性或报告方面的差异。我们的局限性包括回顾性设计和单一机构使用。
查看英文原文 English abstract
BCR-ABL tyrosine kinase inhibitors (TKIs) are used in the treatment of chronic myeloid leukemia (CML) and include second- and third-generation agents: ponatinib, bosutinib, and asciminib. While cutaneous adverse events (cAEs) of first-generation TKIs such as imatinib are well-documented, real-world reports involving newer agents remain limited and poorly described. We therefore aimed to characterize the range of cAEs in patients with CML receiving ponatinib, bosutinib, or asciminib.
We conducted a retrospective chart review queried from the Research Patient Data Registry of Mass General Brigham from 1979 to 2024. We excluded patients without CML or medication use. 291 patients met inclusion criteria, with 92 (32.3%) receiving ponatinib, 182 (62.5%) receiving bosutinib, and 111 (38.1%) receiving asciminib. 37 (12.7%) patients developed a documented cAE, with 1 patient developing 2 different cAEs. There were 38 total discrete cAEs, including rashes (cAEs=38), pruritus (cAEs=20), xerosis (cAEs=5), hyperpigmentation (cAEs=2) and squamous cell carcinoma (SCC) (cAEs=1). All drugs resulted in acneiform eruptions and maculopapular or papular eruptions. Ponatinib also induced pityriasis rubra pilaris-like, keratosis pilaris-like, petechial, and ichthyosiform eruptions. Photosensitive rashes occurred on ponatinib and bosutinib, while pustular eruptions, plaques, and eczematous eruptions occurred on bosutinib and ascimnib. cAEs were treated with topical steroids (cAEs=14), emollients (cAEs=10), and antihistamines (cAEs=9); TKI dose was held or discontinued for 17 events.
The median duration of cAE ranged from 35 days with asciminib to 91.5 days with bosutinib. 60.5% of events presented within 90 days of medication initiation. No patients required hospitalization for the cAEs; the majority were grade 1 severity (57.2%). There was a significant association between female sex and cAE development (OR 3.30, p=0.003), but no association for age, race, ethnicity, prior CML treatments, and initial dosage.
We present a detailed characterization of real-world presentations of cAEs developing on ponatinib, bosutinib, and asciminib, with observed incidence rates of 16.3%, 8.8%, and 6.3%, respectively. The significantly increased risk in females aligns with prior literature, possibly due to differences in body type, medication adherence, or reporting. Our limitations include retrospective design and single institution use.
利益披露 Disclosure
R. Kanwar, None..
J. Khang, None..
G. Sakunchotpanit, None..
R. Nayak, None..
N. R. LeBoeuf, None..
V. E. Nambudiri, None.