Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.

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Background Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment refractory cutaneous lupus erythematosus (CLE). Objectives We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment refractory patients before and after treatment. Patients/Methods Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans and CXCL10, an interferon (IFN)-inducible chemokine, before and after treatment. Immunophenotyping and measurement of IFN-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment. Results Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells and regulatory T-cells, were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of IFN-mediated pathways, regardless of clinical response. Limitations Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets. Conclusions Lenalidomide may have utility as therapy for severe, treatment refractory CLE. However, our preliminary data suggest that lenalidomide may activate T-cells and trigger systemic disease in some CLE patients. We also saw a unique histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment refractory patients will improve our understanding of CLE.