This podcast evaluates results from a phase II clinical trial of pembrolizumab for relapsed Mycosis Fungoides and Sezary Syndrome in the context of the current systemic treatment landscape for this disease.
This JCO Podcast provides observations and commentary on the JCO article "Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sezary Syndrome: A Multicenter Phase II Study" by Khodadoust et al. My name is Jennifer Amengual, and I am an Assistant Professor of Medicine at the Columbia University Irving Medical Center in New York, New York, USA. My oncologic specialty is lymphoma.
Mycosis fungoides, otherwise known as MF, and Sezary Syndrome, its leukemic variant, are rare subtypes of cutaneous T-cell lymphoma. Although most patients with MF have indolent disease, those with advanced stage MF often experience resistance to systemic therapy with a persistent and progressive disease course, which has a negative impact on overall well-being and survival. Patients may have intense pruritus, which can then put them at increased risk for staphylococcus infection, sepsis and in turn can trigger disease flare.
Advanced-stage MF is a chronic disease that is not considered curable; therefore, it is necessary to consider management strategies that provide symptom relief and can be maintained over a long period of time. Most patients cycle through a multitude of therapies, often including skin-directed and, later, systemic therapies. Many of the acceptable therapies are derived from retrospective studies or single-arm trials; therefore, it is not possible to objectively compare outcomes and toxicity. In order to put the outcomes of pembrolizumab in context of other acceptable treatment modalities, I will discuss some of these treatments now.
Systemic retinoids, such as bexarotene, are taken orally and can induce an overall response of 45-55%. The drug is well tolerated but can lead to hypertriglyceridemia and hypothyroidism, requiring monthly monitoring and frequent treatment with lipid-lowering agents and thyroid hormone replacement.
Low-dose methotrexate, administered either orally or by intravenous infusion weekly, can lead to response rates between 30 and 50%. Common side-effects include mucositis, cytopenias and gastrointestinal upset. Pralatrexate is a novel antifolate drug that when studied using half the dose of that which is approved for PTCL , induced a 45% response rate for patients with MF. The treatment is also well tolerated, with the most common side-effects being mucositis and thrombocytopenia.
There are 2 histone deacetylase inhibitors approved for use in MF and Sezary Syndrome. Both romidepsin and vorinostat have overlapping toxicity profiles, including gastrointestinal disturbances, fatigue, anorexia, and cytopenias. Romidepsin is also associated with ECG abnormalities. In patients with cutaneous T cell lymphoma, romidepsin has demonstrated a response rate of 34% and is associated with a median duration of response of 15 months. Vorinostat, an oral drug, has demonstrated a response rate of 30%.
Recently, 2 biologics have been in used for patients with MF. Brentuximab vedotin is an antibody drug conjugate which targets the surface marker CD30 and brings monomethyl auristatin E into the cell. It is associated with a response rate of 70% in MF. Responses are significantly better in those with greater than 5% of CD30 expression. The most common side-effect is peripheral neuropathy. Mogamulizumab is a humanized antibody directed against the chemokine receptor CCR4. This agent was studied in a randomized trial compared to vorinostat, where it led to a PFS of 7.7 months and response rate of 28%. The most common adverse events were attributed to infusion reactions, rash, diarrhea, and fatigue. There was also an increased risk of graft-versus-host disease in patients who subsequently went on to a