■与BRAF/MEK抑制剂的联合治疗有利地影响恶性黑色素瘤的无进展生存期。然而,它可能引起免疫细胞中无BRAF突变的MAPK/ERK通路的矛盾激活,这可能会导致免疫系统过度激活,尤其是在预先存在自身免疫性疾病的患者中。在这个案例报告中,BRAF/MEK抑制剂治疗恶性黑色素瘤与已有多发性硬化(MS)的放射学疾病恶化相关.
■一名患有MS的47岁患者于2020年6月被诊断为恶性黑色素瘤。抗肿瘤治疗开始于BRAF抑制剂dabrafenib和MEK抑制剂trametinib的联合治疗。2022年2月,患者在我们的神经诊所接受常规MRI检查后发现放射学MS疾病活动恶化,并伴有10个新的和钆增强的病变,血清中伴随着高水平的神经丝轻链(NfL),轴突损伤的标记。通过多色流式细胞术对外周血和脑脊液中的免疫细胞进行深入分析。用B细胞消耗抗体ocrelizumab治疗后,获得MS疾病的稳定性,并可以继续抗肿瘤药物治疗。
■从肿瘤的角度来看,癌症患者的免疫调节治疗非常有效,但可能与自身免疫副作用有关。这对于预先存在自身免疫性疾病的患者特别重要,正如我们在BRAF/MEK抑制剂治疗下MS疾病重新激活的病例所反映的那样。在我们的案例中,通过B细胞耗竭对免疫细胞亚群的顺序调节,与B和T细胞亚群的显著变化相关,允许稳定疾病和继续抗肿瘤治疗。
UNASSIGNED: Combination treatment with BRAF/MEK inhibitors favorably impact progression-free survival in malignant melanoma. However, it may cause paradoxical activation of the MAPK/ERK pathway in immune cells without BRAF mutation, which may lead to over activation of the immune system, especially in patients with pre-existing autoimmune conditions. In this
case report, treatment of malignant melanoma with BRAF/MEK inhibitors was associated with radiological disease exacerbation of pre-existing multiple sclerosis (MS).
UNASSIGNED: A 47-year-old patient with pre-existing MS was diagnosed with malignant melanoma in June 2020. Anti-tumor treatment was initiated with a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. In February 2022, the patient presented at our neurological clinic after routine MRI revealed exacerbation of radiological MS disease activity with ten new and gadolinium-enhancing lesions, and concomitant high levels of neurofilament light chain (NfL) in serum, a marker for axonal damage. In-depth analysis of immune cells in both peripheral blood and cerebrospinal fluid was performed by multi-color flow cytometry. After treatment with the B cell-depleting antibody ocrelizumab, MS disease stability was obtained and anti-tumor medication could be continued.
UNASSIGNED: Immunomodulatory treatment in cancer patients is highly effective from an oncological point of view, but may be associated with autoimmune side effects. This is of special importance in patients with pre-existing autoimmune diseases, as reflected by our
case of MS disease reactivation under treatment with BRAF/MEK inhibitors. In our
case, sequential modulation of immune cell subsets by B cell depletion, associated with marked shifts in B and T cell subsets, allowed for stabilization of disease and continuation of anti-tumor treatment.