Alemtuzumab holds promise for treatment of advanced CTCL

New immune therapies with new targets that can induce long-term remission in patients with advanced cutaneous T-cell lymphoma (CTCL) are needed, says an expert.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common forms of CTCL. Their management can be challenging as treatment modalities span the disciplines of dermatology, medical oncology and radiation oncology. Apart from allogeneic stem cell transplantation, there are currently no curative therapies for CTCL. [Drugs 2010;70:273-286]

“Monoclonal antibodies are promising agents as they are either tumor cell-specific, targeting tumor surface molecules, or immunomodulating, acting on the microenvironment of the tumor,” said Dr. Martine Bagot of the Department of Dermatology at Hospital Saint-Louis in Paris, France.

Alemtuzumab is a humanized immunoglobulin G1 kappa monoclonal antibody specific for the CD52 antigen expressed by most T and B lymphocytes. “A high dosage [30 mg three times per week] has been shown effective in treating SS, but it was also associated with significant immunosuppressive toxicity,” said Bagot. [Eur J Haematol 2003;7:250-256]

In their multicenter retrospective analysis on 39 patients with SS or advanced MF treated with alemtuzumab between 2003 and 2013, eight patients (21 percent) were alive at a median follow-up of 24 months. “The overall response rate was 51 percent in the whole study group, 70 percent in patients with SS and 25 percent in patients with MF. Six patients remained progression-free for more than 2 years,” she reported. [Br J Dermatol 2014;170:720-724]

“Sixty-two percent of the patients had a grade 3 or higher infectious adverse event and 26 percent had hematologic toxicity, which led to treatment discontinuation in 17 patients and death in two. This could have been due to the high dosage of alemtuzumab used in the study [30 mg],” noted Bagot. “Based on these results, we concluded that alemtuzumab may induce long-term remission in patients with SS, but is ineffective in MF and the 11 patients with transformed CTCL.”

In an earlier study in patients with SS, low-dose subcutaneous alemtuzumab (10 mg, given for a short period based on Sézary cell levels) demonstrated a good toxicity profile, high response rates (86 percent clinical response), and durable remissions in SS patients with high tumor burden. [Haematologica 2007;92:784-794]

After a median follow-up of 16 months, infectious complications occurred in 29 percent of patients treated with alemtuzumab 15 mg, but no patient receiving the 10 mg dose developed hematologic
toxicity or infections.

“Thus, a protocol of lower dose administration is recommended to minimize immune suppression and infections,” said Bagot.