Advanced-Stage Mycosis Fungoides: Navigating Treatment Decisions Amid a Complex Therapeutic Landscape

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Patient-specific factors significantly influence treatment selection in advanced CTCL, including comorbidities, response timelines, and drug accessibility. The compartmental approach to therapy selection considers whether patients have circulating disease, Sézary syndrome, or specific anatomical involvement patterns. Mogamalizumab, HDAC inhibitors, and alemtuzumab demonstrate particular efficacy in patients with circulating disease, while showing limited skin-directed activity compared to agents like brentuximab vedotin.

HDAC inhibitors, including romidapsin (intravenous) and vorinostat (oral), provide therapeutic options for patients with both peripheral blood and nodal involvement. These agents represent valuable treatment choices when patients present with multi-compartment disease involvement. However, careful consideration of patient comorbidities is essential - avoiding HDAC inhibitors in patients with congestive heart failure and brentuximab vedotin in those with pre-existing neuropathy ensures optimal treatment safety profiles.

Checkpoint inhibitors, particularly PD-1 inhibitors, have shown limited efficacy in T-cell lymphomas compared to other hematologic malignancies. While some combination approaches with conventional therapies show promise, the overall response rates remain disappointing. A significant concern with PD-1 inhibitors in erythrodermic patients is the potential for severe disease flares, requiring careful monitoring and management. PI3 kinase inhibitors show preliminary activity but carry risks of transaminitis and autoimmune complications, with sequential therapy considerations important for minimizing enhanced toxicity risks.