The Microbiome in Advanced Melanoma: Where Are We Now?

Purpose Of Review: This review summarizes recent data linking gut microbiota composition to ICI outcomes and gut microbiota-specific interventional clinical trials in melanoma.

Recent Findings: Preclinical and clinical studies have demonstrated the effects of the gut microbiome modulation upon ICI response in advanced melanoma, with growing evidence supporting the ability of the gut microbiome to restore or improve ICI response in advanced melanoma through dietary fiber, probiotics, and FMT. Immune checkpoint inhibitors (ICI) targeting the PD-1, CTLA-4, and LAG-3 negative regulatory checkpoints have transformed the management of melanoma.

Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.

The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult.

A Pilot Study of Lenalidomide Maintenance Therapy after Autologous Transplantation in Relapsed or Refractory Classical Hodgkin Lymphoma.

For patients with relapsed or refractory classical Hodgkin lymphoma (cHL), salvage chemotherapy followed by consolidation with autologous stem cell transplant (ASCT) remains the standard of care. Even with this aggressive treatment strategy, 5-year progression-free survival is ≤50%, and there remains interest in maintenance strategies to improve long-term disease-free survival. Lenalidomide is an immunomodulatory agent with demonstrated activity in multiple subtypes of lymphoma including cHL, and has also been shown to improve both progression-free and overall survival as maintenance therapy after ASCT in multiple myeloma.