Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB-IV M1c melanoma patients
Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB-IV M1c melanoma patients
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DOI：
10.1007/s00262-020-02487-x
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发表时间：
2020-02-12
影响因子：
5.8
通讯作者：
Landsberg, Jennifer
中科院分区：
文献类型：
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作者：
Froehlich, Anne;Niebel, Dennis;Landsberg, Jennifer
背景黑色素瘤患者对免疫检查点阻断和靶向治疗的抵抗是目前临床面临的主要挑战之一。随着talimogene laherparepvec(T-VEC)的批准，溶瘤病毒现已用于治疗局部晚期或不可切除的黑色素瘤。在此，我们描述了T-VEC在IVM1b-M1c期黑色素瘤患者中的应用，这些患者经系统治疗后完全缓解或病情稳定，但局部复发。据我们所知，到目前为止还没有病例报告将T-VEC描述为克服对免疫检查点阻断或靶向治疗的获得性抵抗的一种手段。方法回顾分析2016-2018年我科采用T-VEC治疗的所有黑色素瘤患者的临床资料。分析临床病理特征、治疗反应和毒性的数据。结果14例黑色素瘤患者接受了T-VEC治疗。6例患者(43%)接受T-VEC一线治疗。在8名患者(57%)中，T-VEC遵循先前的系统治疗。3例M1b期和1例M1c期黑色素瘤患者接受了T-VEC治疗。这些患者患有局部进展，而远处转移在先前的系统治疗中已经消退。%的患者表现出从T-VEC治疗中受益。持久有效率为36%。结论T-VEC是一种有效且可耐受的治疗方法。这不仅适用于局部进展性黑色素瘤患者，也适用于经免疫检查点阻断或靶向治疗后出现局部获得性耐药的稳定性或退行性全身转移患者。合理选择合适的患者似乎是至关重要的。
Background Resistance to immune checkpoint blockade and targeted therapy in melanoma patients is currently one of the major clinical challenges. With the approval of talimogene laherparepvec (T-VEC), oncolytic viruses are now in clinical practice for locally advanced or non-resectable melanoma. Here, we describe the usage of T-VEC in stage IVM1b-M1c melanoma patients, who achieved complete remission or stable disease upon systemic treatment but suffered from a loco-regional recurrence. To our knowledge, there are no case reports so far describing T-VEC as a means to overcome acquired resistance to immune checkpoint blockade or targeted therapy. Methods All melanoma patients in our department treated with T-VEC in the period of 2016-2018 were evaluated retrospectively. Data on clinicopathological characteristics, treatment response, and toxicity were analyzed. Results Fourteen melanoma patients were treated with T-VEC in our center. Six patients (43%) received T-VEC first-line. In eight patients (57%), T-VEC followed a prior systemic therapy. Three patients with M1b stage and one patient with M1c stage melanoma were treated with T-VEC. These patients suffered from loco-regional progress, whilst distant metastases had regressed during prior systemic treatment. 64% of patients showed a benefit from therapy with T-VEC. The durable response rate was 36%. Conclusion T-VEC represents an effective and tolerable treatment option. This is true not only for loco-regionally advanced melanoma patients, but also for patients with stable or regressive systemic metastases who develop loco-regionally acquired resistance upon treatment with immune checkpoint blockade or targeted therapy. A sensible selection of suitable patients seems to be crucial.