Remission of primary cutaneous anaplastic large cell lymphoma after a brief course of brentuximab vedotin

Abstract

Dear Editor, We evaluated a 74-year-old Caucasian man with multiple previous recurrences of primary cutaneous anaplastic large cell lymphoma (PCALCL) between 2003 and 2010 involving his scalp, forearms, shoulders, and trunk as solitary papules or nodules. They had been treated with excisions, topical carmustine, or focal electron beam radiotherapy (EBRT). In 2011, the patient received 4,000-cGy EBRT to a new lesion on the left calf and 3,600-cGy tomotherapy to adjacent tumors in January 2012. Treatment was complicated with extensive lymphedema, cellulitis, and ulcerative dermatitis requiring debridement, intravenous antibiotics and resulting in nonhealing wounds. In June 2012, numerous rapidly growing nodules appeared on the patient’s left thigh, without evidence of systemic involvement (Fig. 1a). Biopsy consistently demonstrated CD30-positive, anaplastic lymphoma kinase (ALK-1)-negative PCALCL (Fig. 1b). This multifocal recurrence necessitated systemic therapy, but the disease progressed with enlarging and new lesions within 3 weeks of starting oral methotrexate 15 mg weekly. Multiagent chemotherapy was considered hazardous in view of ongoing, debilitating wound complications. The patient consented to off-label treatment with brentuximab vedotin and received three infusions at 1.8 mg/kg every 21 days. All lesions regressed completely during the first cycle (Fig. 1c). No toxicity was observed except for grade 1 diarrhea lasting 7 days. In particular, no neutropenia or neuropathy occurred. The patient has been in continued remission for 3 months and continued recovery of mobility with specialized wound care. PCALCL differs from other cutaneous T cell lymphomas such as mycosis fungoides and from the systemic form of ALCL. It is composed of large anaplastic, pleomorphic, or immunoblastic T cells typically expressing CD30, but not ALK-1, and runs an indolent course with frequent, though limited cutaneous recurrences [1]. Therapy for this rare disease relies on case reports and series, particularly for the minority of patients with multifocal relapses or nodal involvement [2]. Surgical excision and radiotherapy have a curative potential for solitary lesions. Remissions with cytotoxic chemotherapy, occurring rapidly even after low-dose methotrexate or etoposide, are disappointingly short (months) in refractory cases, although retreatment is often successful [3–5]. Anecdotal responses to imiquimod, bexarotene, retinoids, interferon, and thalidomide have been reported [2]. Brentuximab vedotin is an anti-CD30 monoclonal antibody conjugate with a potent microtubule inhibitor monomethyl auristatin E [6]. With up to 16 doses in the pivotal phase II studies, it produced the remarkable 75 % response rate in refractory CD30-positive Hodgkin’s lymphomas relapsing after autologous stem-cell transplantation, and 86 % in recurrent systemic ALCL [7, 8]. Toxicities include peripheral sensory neuropathy, neutropenia, fatigue, nausea, and rare occurrences of progressive multifocal leukoencephalopathy in immunosuppressed patients [9]. The unconjugated anti-CD30 antibody SGN-30 had demonstrated activity against PCALCL, but its development was abandoned [10]. Although cost concerns limit the application of targeted therapy in PCALCL, our case may indicate that in patients medically unsuitable for combination chemotherapy, A. Desai :A. J. Olszewski (*) Division of Hematology–Oncology, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860, USA e-mail: adam_olszewski@brown.edu