A Case of Refractory Sézary Syndrome With Large-Cell Transformation Responsive to Brentuximab Vedotin

Brentuximab vedotin is a CD30-directed antibody/drug conjugate recently approved for the treatment of relapsed Hodgkin lymphoma (HL) and systemic anaplastic large-cell lymphoma (ALCL). Given that CD30 is variably expressed in mycosis fungoides (MF) and Sézary syndrome (SS), brentuximab vedotin is a promising treatment option for these cutaneous neoplasms. Initial studies have confirmed its clinical activity in refractory cases.

An 85-year-old white woman with early dementia presented with 6 months of fatigue, weight loss, and diffuse pruritic violaceous patches and plaques (Figure 1A). Findings from lymph node examination were unremarkable. Biopsies of a patch and plaque on the back revealed a dense bandlike infiltrate of atypical lymphocytes in the dermis with large and irregular forms (Figure 2A). Atypical lymphocytes extended into the epidermis arranged along the dermal-epidermal junction and within the Pautrier microabscesses (Figure 2B). Immunohistochemical staining characterized the lymphocytic population as CD3⁺ T-lymphocytes with a predominance of CD4⁺ over CD8⁺ cells. Expression of CD7 was decreased. Loose aggregates of enlarged dermal lymphocytes, making up approximately 25% of the lymphoid infiltrate, showed CD30 positivity (Figure 2C). Anaplastic lymphoma kinase staining was negative. A complete blood cell count was within normal limits. The lactate dehydrogenase level was normal at 522 U/L. Peripheral flow cytometry revealed immunophenotypically abnormal CD4⁺ T-cells with reduced CD2 and CD3 expression and loss of CD7 making up 42% of the total lymphocytes. These findings were suggestive of stage IVA (T3B2) SS with large-cell transformation.

The patient was started on bexarotene treatment but experienced progressive cognitive decline after 4 weeks. Her disease continued to progress rapidly with enlarging pruritic plaques on her trunk and disfiguring confluent nodules on her face causing leonine facies (Figure 1B). A 2-month trial of narrowband UV-B phototherapy with topical steroids and several local radiation treatments were ineffective. Two months of alemtuzumab therapy resulted in cytomegalovirus viremia without improvement in skin lesions.

Since a significant proportion of the lymphoid infiltrate expressed CD30, brentuximab vedotin therapy was approved and initiated at a dose of 1.2 mg/kg followed by 1.4 mg/kg every 3 weeks. After 5 cycles, regression of nodules and plaques was observed, and the patient reported significantly decreased pruritus (Figure 1C). She denied any adverse effects, including nausea and neuropathy. Of note, she developed a pink crateriform tumor with central ulceration during treatment, which was found to be consistent with tumor stage MF. Immunohistochemical staining of this tumor was positive for CD3 and CD4 with rare large cells positive for CD30.

Brentuximab vedotin demonstrates antitumor activity against malignant cell types expressing CD30 in relapsed HL and systemic ALCL.¹ In addition to HL and ALCL, the CD30 cell surface receptor is expressed in cutaneous neoplasms including lymphomatoid papulosis and MF/SS. In MF/SS, CD30 expression is associated with late-stage disease and large-cell transformation, but variable expression of CD30 can occur at all stages.² Therefore, targeting CD30 with use of brentuximab represents a promising therapeutic strategy in MF/SS.

Clinical trials are ongoing to determine the efficacy of brentuximab in MF/SS. The results of a pilot study of 19 patients suggest that brentuximab has significant clinical activity in patients with MF/SS across all levels of CD30 expression.³ A recently presented case series described 1 patient with CD30⁺ MF who showed a complete response to brentuximab vedotin.⁴ To our knowledge, this is the first case report of successful brentuximab vedotin use in a patient with SS with large-cell transformation and CD30 positivity. Our patient developed a solitary tumor during treatment that was mostly CD30⁻, indicating that CD30⁺ cells were effectively targeted during brentuximab treatment. Further studies are needed to elucidate the role of brentuximab therapy in MF/SS and other cutaneous CD30⁺ lymphoproliferative disorders.

Corresponding Author: Julie H. Lin, MD, Division of Dermatology, University of Vermont College of Medicine, 111 Colchester Ave, Burlington, VT 05401 (Julie.Lin@vtmednet.org).

Published Online: December 18, 2013. doi:10.1001/jamadermatol.2013.5741.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We would like to thank Laura McGevna, MD, of the Division of Dermatology, and Paul Larson, NP, and Barbara Grant, MD, of the Division of Hematology/Oncology at University of Vermont College of Medicine for their help and expertise in caring for our patient. We would also like to thank the patient and her family for allowing us to publish this information.