Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sézary syndrome

Abstract

This phase 2 study evaluated the safety and efficacy of alemtuzumab in 22 patients with advanced mycosis fungoides/ Sé zary syndrome (MF/SS). Most patients had stage III or IV disease, reduced performance status, and severe itching. The overall response (OR) rate was 55%, with 32% of patients in complete remission (CR) and 23% in partial remission (PR). Sé zary cells were cleared from the blood in 6 of 7 (86%) patients, and CR in lymph nodes was observed in 6 of 11 (55%) patients. The effect was better on erythroderma (OR, 69%) than on plaque or skin tumors (OR, 40%) and in patients who had received 1 to 2 previous regimens (OR, 80%) than in those who had received 3 or more prior regimens (OR, 33%). Itching, self-assessed on a 0 to 10 visual analog scale, was reduced from a median of 8 before treatment to 2 at end of therapy. Median time to treatment failure was 12 months (range, 5-32؉ months). Cytomegalovirus (CMV) reactivation (causing fever without pneumonitis and responding to ganciclovir) occurred in 4 (18%) patients. Six additional patients had suspect or manifest infection (fever of unknown origin, 3; generalized herpes simplex, 1; fatal aspergillosis, 1). One patient had fatal Mycobacterium pneumonia at 10؉ months. All serious infectious adverse events (except CMV) occurred in patients who had received 3 or more prior regimens. Progression of squamous cell skin carcinoma was noted in 1 patient.

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“…Similar results, with no infectious complications, were recently reported in a small cohort of patients treated with modified, low-dose, subcutaneous alemtuzumab for 6 weeks [321]. In addition to hematologic toxicity, conventionally dosed alemtuzumab in advanced-stage MF/SS is associated with a high incidence of infectious complications [319,320,[322][323][324][325]. Overall, infectious complications have been observed in twothirds of treated patients, most of which are bacterial, including sepsis.…”

“…Alemtuzumab is a humanized IgG1 monoclonal antibody directed against CD52, an antigen widely expressed by B-cells, T cells, and monocytes [318]. In a phase II study in 22 patients with advanced-stage MF/SS, overall and complete response rates of 55 and 32%, respectively, were observed, with a median time to treatment failure of 1 year [319]. Given the significant risk of infectious complications, low-dose subcutaneous alemtuzumab was investigated in 14 patients with SS, most of whom had relapsed/refractory disease [320].…”

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

“…Lundin and colleagues conducted a phase II study of alemtuzumab in 22 patients with advanced MF/SS. 74 The ORR was 55%; 32% of patients achieved a CR and 23% a PR. Sé zary cells were cleared from the blood in 6 of 7 (86%) patients, and CR in lymph nodes was observed in 6 of 11 (55%) patients.…”

“…73 Alemtuzumab is usually administered at a dose of 30 mg intravenously three times per week, following an initial dose-escalation phase, for up to 12 weeks. 30,74 In studies in patients with MF/SS to date, the most common adverse events were opportunistic infections and neutropenia, which can be severe. 30,74 Recently, Lenihan and colleagues suggested that severe cardiotoxicity may be a significant complication of alemtuzumab treatment in MF/SS.…”

“…Sé zary cells were cleared from the blood in 6 of 7 (86%) patients, and CR in lymph nodes was observed in 6 of 11 (55%) patients. 74 Kennedy and colleagues treated 8 patients with relapsed or refractory advanced-stage CTCL with alemtuzumab. 132 Patients were given alemtuzumab (30 mg) intravenously three times per week for 12 weeks or until maximum response.…”