No 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.

This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n ¼ 67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (Po0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase X2 g/dl was significantly higher in the iron group (93%) than in the noiron group (53%) (per-protocol population; P ¼ 0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P ¼ 0.029) and after 15 weeks approximately 10 000 IU (425%) lower in the iron group, as was the total epoetin dose (P ¼ 0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

Patients with peripheral T-cell lymphomas (PTLs) have an extremely poor prognosis when relapsed or refractory to conventional chemotherapy. We have studied alemtuzumab, a humanized anti-CD52 monoclonal antibody, as therapy for patients with heavily pretreated and refractory PTL. Fourteen patients entered the study. All had clinical stage III or IV disease. Patients received a rapidly escalating dosage of alemtuzumab during the first week and, thereafter, 30 mg intravenously 3 times per week for a maximum of 12 weeks. Trimethoprim/sulphamethoxazole and valaciclovir prophylaxis was given to all patients. The overall response rate was 36% (5 of 14). Three patients achieved a complete remission (CR) and 2 patients a partial remission. The durations of the CRs were 2, 6, and 12 months, respectively. Toxicity included cytomegalovirus reactivation in 6 patients, which was successfully treated with ganciclovir or foscarnet; pulmonary aspergillosis in 2 patients; and pancytopenia in 4 patients. Epstein-Barr virus-related hemophagocytosis was observed in 2 patients. Five patients died of causes related to the treatment, in combination with advanced disease. We conclude that alemtuzumab is active when used in patients with advanced, heavily pretreated PTL, although it is associated with significant hematologic toxicity and infectious complications. Further studies are warranted in younger patients and patients with less advanced disease. (Blood. 2004;103: 2920-2924)