Department of Medicine, 541618Eisenhower Health, Rancho Mirage, CA, USA.
Department of Infectious Disease, 541618Eisenhower Health, Rancho Mirage, CA, USA.
J Oncol Pharm Pract. 2022 Dec;28(8):1917-1921. doi: 10.1177/10781552221087730. Epub 2022 Mar 21.
Zanubrutinib is a second generation, irreversible small-molecule Bruton tyrosine kinase inhibitor (BTK) approved for the treatment of Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. As a class, BTKs have been linked with an increased risk of respiratory infections in clinical trials.
We describe a 75-year-old patient who presented with generalized weakness, fevers, dyspnea, and dry cough four months after starting zanubrutinib therapy for Waldenström's macroglobulinemia. He was subsequently diagnosed with pneumonia. Septic work-up led to diagnosis of disseminated cryptococcal infection, complicated by fungal pneumonia and meningitis.
Zanubrutinib was held on admission, and the patient was started on combination oral and intravenous antifungal therapy. Despite clearance of fungemia, aggressive resuscitation, and appropriate antimicrobial therapy, respiratory status deteriorated requiring intubation. His condition progressed to septic shock, multiorgan failure, and demise.
DISCUSSION/CONCLUSION: We report herein a case of fatal disseminated cryptococcosis in the setting of zanubrutinib use for Waldenström's macroglobulinemia. At the time of diagnosis, his Waldenström's macroglobulinemia was in a partial response. The mechanism by which Bruton tyrosine kinase inhibitors (BTKs) lead to invasive fungal infections in these patients remains to be explored. T- and B-cell immune defects accompanying low-grade B-cell lymphomas may contribute to the severity of these infections.
泽布替尼是第二代、不可逆的小分子布鲁顿酪氨酸激酶抑制剂（BTK），已获批用于治疗华氏巨球蛋白血症、套细胞淋巴瘤和边缘区淋巴瘤。在临床试验中，BTK 类药物已被发现与呼吸道感染风险增加相关。
我们描述了一例 75 岁患者，在开始使用泽布替尼治疗华氏巨球蛋白血症四个月后，出现全身乏力、发热、呼吸困难和干咳。随后被诊断为肺炎。全身感染性检查提示播散性隐球菌感染，并发真菌性肺炎和脑膜炎。
入院时停用泽布替尼，并开始联合口服和静脉抗真菌治疗。尽管真菌血症清除、积极复苏和适当的抗菌治疗后，患者的呼吸状况仍恶化，需要插管。他的病情进展为感染性休克、多器官衰竭和死亡。
讨论/结论：我们在此报告一例华氏巨球蛋白血症患者在使用泽布替尼治疗期间发生致命性播散性隐球菌病。在诊断时，他的华氏巨球蛋白血症处于部分缓解期。布鲁顿酪氨酸激酶抑制剂（BTKs）导致这些患者发生侵袭性真菌感染的机制仍有待探索。伴随低级别 B 细胞淋巴瘤的 T 细胞和 B 细胞免疫缺陷可能导致这些感染的严重程度增加。
