ASO Author Reflections: Mixed Response in Metastatic Melanoma Patients Treated with Immunotherapy

Excerpt

The advent of immune checkpoint inhibitors has revolutionized the therapeutic landscape of metastatic melanoma and has resulted in significant improvements in patient survival. Systemic anti-programmed cell death protein blocking antibodies (anti-PD-1) demonstrated improved overall survival as compared with ipilimumab (anti-CTLA-4),1, 2 and the combination of anti-PD-1 and anti-CLTA-4 therapy is associated with a higher response rate and longer survival in patients with metastatic melanoma.3 However, it is clear that radiographic response via Response Evaluation Criteria in Solid Tumors (RECIST 1.1) may be insufficient to characterize the heterogeneous tumoral responses seen with immunotherapy, hence the creation of iRECIST, a guideline standardizing radiographic approaches to tumor measurements and changes during treatment.4 It has been observed that a subset of patients has a mixed response in which an individual can have synchronous regression in some tumors with progression in others: a very interesting biological phenomenon. This is distinct from pseudoprogression, a scenario in which tumors will increase in size but eventually regress, thought to be due to initial immune infiltration in the tumors prior to regression. Other patients have lesions that may regress or remain stable for a long period of time (i.e., RECIST stable disease), leaving the biological significance of those tumors unclear. Yet other patients progress in a single site or organ after a good response to therapy, termed oligoprogression. These heterogeneous immunotherapy responses are challenging and currently clinical decisions for these situations are made on a case-by-case basis. …