Department of Allergology "Carol Davila", University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Department of Allergy and Clinical Immunology, "Dr. Carol Davila" Nephrology Clinical Hospital, 010731 Bucharest, Romania.
Medicina (Kaunas). 2022 Apr 3;58(4):511. doi: 10.3390/medicina58040511.
Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.
达布拉非尼和曲美替尼是两种已被批准用于治疗携带 BRAF-V600E 或 V600K 突变的转移性黑色素瘤的药物。它们的联合治疗带来了持久的生存获益，并显著改善了预后。到目前为止，只有少数报道了对达布拉非尼和维莫非尼严重过敏反应的病例，而且针对这些药物的脱敏方案也很少有记录。我们报告了一例 71 岁女性转移性黑色素瘤患者，携带 BRAF-V600E 突变，接受达布拉非尼和曲美替尼的靶向治疗。在联合治疗开始两周后，她出现了过敏反应。达布拉非尼和过敏反应之间的因果关系通过两次试验得到了证实，当重新引入达布拉非尼时，症状再次出现。我们开始了一个快速的 3 天达布拉非尼脱敏方案，该方案耐受良好。当患者停止药物治疗时，我们决定采用一个更长的方案，包括更多的步骤和更多的天数，以防止其他过敏反应的发生。我们的患者耐受了快速和缓慢脱敏方案，第一种方案在 3 天内达到了最终剂量，第二种方案在 14 天内达到了每日总剂量。根据患者的需求、过敏反应的严重程度和医院的可用性，医生可能会选择快速或缓慢脱敏方案。
