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Dr Johnson on Treatment Gaps With Immunotherapy in Melanoma

Douglas B. Johnson, MD, MSCI, highlighted avenues for improving immunotherapy use in melanoma during Cancer Immunotherapy Awareness Month.

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    "[In melanoma], we're still seeing a 10% to 30% response rate in the frontline setting. There are still a lot of challenges. We've come a long way, but [still have] a long way to go."

    Douglas B. Johnson, MD, MSCI, a professor of medicine in the Division of Hematology/Oncology and leader of the Melanoma Clinical Research Program at Vanderbilt University Medical Center, outlined ongoing challenges and unmet needs in the immuno-oncology landscape for melanoma, despite advances in immune checkpoint inhibition.

    Although many patients with metastatic melanoma achieve responses with frontline immunotherapy, approximately half derive limited or no benefit, underscoring the need for more effective primary and salvage treatment strategies, Johnson began.

    A major gap in the current treatment paradigm is the absence of reliable biomarkers to predict response, making it difficult to identify patients who are less likely to benefit from immune checkpoint inhibitors in advance, he stated. In response, the field is increasingly focused on cellular therapy approaches for immunotherapy-refractory disease, Johnson reported. Tumor-infiltrating lymphocyte (TIL) therapy, such as lifileucel (Amtagvi), the first FDA-approved TIL product, has demonstrated response rates between 30% to 50% in this setting. Additional investigational agents, including next-generation TIL products, aim to enhance efficacy while improving tolerability. They can also help simplify treatment logistics through eliminating the need for high-dose interleukin-2, for example, Johnson explained.

    Emerging T-cell receptor T-cell (TCR-T) therapies represent another novel approach, Johnson continued. Unlike TILs, these therapies can be derived from peripheral blood, reducing the need for surgical tumor resection. For example, the PRAME-targeted TCR-T cell therapy IMA203 has shown early response rates near 50% in HLA-A*02:01–positive patients, although applicability is limited by HLA restriction, he noted. This agent is currently being evaluated in the registrational phase 3 SUPRAME trial (NCT06743126).

    Johnson concluded by stating that although melanoma remains a model disease for immunotherapy success, substantial work remains, both in improving first-line efficacy and in developing new strategies for patients who relapse or are refractory. 


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