Immunotherapy Response in Advanced Melanoma: Effect of Previous Treatments

According to a study conducted by UCLA Jonsson Comprehensive Cancer Center researchers, patients with advanced melanoma responded differently to PD-1 checkpoint blockade immunotherapy depending on a variety of variables, including whether or not they had previously received CTLA-4 blockade, another type of immunotherapy.

They reported their findings in Cancer Cell after analyzing seven data sets collected over the previous ten years that comprised the tumor biopsy results of more than 500 individuals.

In our large set of data, features that have been used to predict response to anti-PD-1 checkpoint blockade therapy—often called biomarkers—related to the presence of certain immune cell types in the tumor and the genetic profile of the tumors themselves were modified by a patient’s treatment history.”

Katie Campbell, PhD, Study Lead Author and Postdoctoral Fellow, Hematology/Oncology, UCLA Jonsson Comprehensive Cancer Center

Immune therapies such as anti-PD-1 blockade and anti-CTLA-4 blockade are frequently used to treat patients who have been diagnosed with advanced melanoma, either in combination or separately. These checkpoint inhibitors improve the body’s immune response to cancer by inhibiting certain proteins that reduce the potency of T cells.

Campbell stated, “As translational scientists, when we work with clinicians, one of the goals is to think about how biomarkers can be used to inform clinical benefit. If we can predict which patients are or are not going to respond to therapy from studying their biopsies, we can start to more strategically define which therapies or combinations of therapies should be used and when.”

Study co-senior author Dr Antoni Ribas, director of the Tumor Immunology Program at UCLA Jonsson Comprehensive Cancer Center and the Parker Institute for Cancer Immunotherapy Center at UCLA, added, “Since the current treatment paradigm for melanoma involves combinations or sequential use of immune checkpoint therapies, our study supports how these therapies may work together to effectively treat melanoma. It also highlights the importance of a patient’s prior treatment history as a modifying factor to consider when planning a treatment strategy.”

Despite the fact that late-stage cancers are being treated with immunotherapy, the majority of research on biomarkers and variables affecting effectiveness are based on limited series of samples.

Due to this, the interdisciplinary and multicenter research team set out to compile and harmonize a large set of tumor and clinical data from melanoma patients to discover important variables linked to treatment response.

Campbell pointed out, “The cohesive processing of clinical data sets requires collaboration among experts with knowledge in computer science, statistics, biology, immunotherapy, informatics, and translational and clinical medicine. We undertook this project to establish a resource for other researchers, with the goal of identifying statistically significant correlates of melanoma responses to anti-PD-1 therapy.”

“As we performed the analyses, the greatest differences were seen when we accounted for a patient’s prior treatment with anti-CTLA-4 blockade the context in which a biopsy is collected needs to be considered to better define how biomarkers should be implemented in the clinical setting,” she added.

According to the students, by processing the DNA and RNA sequencing data from hundreds of patients using a single, well-organized pipeline, they were able to account for some of the vast disparities between individuals, tumors, and treatment histories.

To determine why a patient responded or did not respond to anti-PD-1 blockade therapy, they also took into account clinical demographics.

Although the findings do not precisely state how or when to utilize the biomarker information in therapeutic settings, they do offer a framework and a sense of direction.