Factors Determining Long-Term Antitumor Responses to Immune Checkpoint Blockade Therapy in Melanoma

Abstract

With the increasing promise of long-term survival with immune checkpoint blockade (ICB) therapies, particularly for patients with advanced melanoma, clinicians and investigators are driven to identify prognostic and predictive factors that may help to identify individuals who are likely to experience durable benefit. Several ICB combinations are being actively developed to expand the armamentarium of treatments for patients who may not achieve long-term responses to ICB single therapies alone. Thus, negative predictive markers are also of great interest. This review seeks to deepen our understanding of the mechanisms underlying the durability of ICB treatments. We will discuss the currently available long-term data from the ICB clinical trials and real-world studies describing the survivorship of ICB-treated melanoma patients. Additionally, we explore the current treatment outcomes in patients rechallenged with ICB and the patterns of ICB resistance based on sites of disease, namely, liver or CNS metastases. Lastly, we discuss the landscape in melanoma in the context of prognostic or predictive factors as markers of long-term response to ICB.

Long‐term survival of dogs with stage 4 oral malignant melanoma treated with anti‐canine PD‐1 therapeutic antibody: A follow‐up case report

“…Similarly, human clinical studies of ICIs revealed that most patients who discontinued treatment due to adverse events still achieved prolonged CR or continued lack of progression during long‐term follow‐up 21–23 . This long‐term response may be due to the generation of memory adaptive antitumor immunity in different populations of immune cells 24,25 …”

“…[21][22][23] This long-term response may be due to the generation of memory adaptive antitumor immunity in different populations of immune cells. 24,25 The long-term survival induced by ICIs could increase the possibility of developing secondary cancer by prolonging life-span. Administration of ICIs is associated with a decreased incidence of secondary cancer, based on a large exhaustive database.…”

Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy

“…Previous studies have shown that clinical parameters, such as PD-L1 expression level, tumor histology, and anti-PD-1 monotherapy, are significantly associated with ICI treatment efficacy ( 24 , 25 ). Our findings are consistent with those studies, implying that our findings are reliable.…”

Bildgestützte Beurteilung des Ansprechens auf Immuntherapien bei Hauttumoren

“…Insbesondere im Rahmen von Immuntherapien haben jedoch Zusammensetzung und Verteilung des Immuninfiltrats im Tumor großen Einfluss auf das Therapieansprechen. 21 So bestimmt die Verteilung der T-Zellen im Tumor und seiner Peripherie wesentlich den Therapieerfolg. 22 Die funktionelle Bildgebung, zum Beispiel mittels PET, kombiniert die Vorteile von funktioneller Charakterisierung und räumlicher Information.…”

“…Computertomographie, MRT und Sonographie sind Morphologie‐basierte Bildgebungsstrategien. Insbesondere im Rahmen von Immuntherapien haben jedoch Zusammensetzung und Verteilung des Immuninfiltrats im Tumor großen Einfluss auf das Therapieansprechen 21 . So bestimmt die Verteilung der T‐Zellen im Tumor und seiner Peripherie wesentlich den Therapieerfolg 22 .…”