Rate of infection and immunosuppression in two phase III studies of denileukin diftitox (DD) in cutaneous T-cell lymphoma (CTCL).

Abstract

e18515 Background: CTCL patients are at increased risk for infection because of the disruption of the skin barrier and immunosuppression due to the disease itself. Infection is the cause of death in 30%-60% of patients and cytotoxic chemotherapies used for advanced and refractory patients are associated with myelosuppression and further compromise of immune function. Methods: We evaluated immunosuppression and infections in 223 patients with stage Ia-III CTCL treated with DD or placebo (PBO) in two multicenter clinical trials. In both trials, DD was administered in doses of 9 or 18 μ g/kg IV, daily for 5 days, every 21 days for up to 8 courses. Evaluations included absolute lymphocyte count (ALC), absolute neutrophil count (ANC), and rate of infection in patients with mycosis fungoides (MF, n=201) and Sezary syndrome (SS, n=22). Results: Of 223 patients, 43 received PBO, 43 DD 9 μ g/kg, and 137 DD 18 μ g/kg. Repeated courses of DD were not associated with immunosuppression as manifested by fungal, viral, or bacterial infections. Infections experienced by CTCL patients with MF decreased steadily from course 1 to course 8: 1.347 to 0.086 events per patient, 1.293 to 0.059, and 0.452 to 0.125 for DD responders, DD nonresponders, and PBO nonresponders respectively. ALC decreased in DD patients during the first treatment course, then rebounded and remained at normal levels after course 2. ANC increased during the first course, but returned to normal thereafter. Adverse events generally showed a pattern consistent with the status of the CTCL disease. Conclusions: In these clinical trials, DD does not appear to be immunosuppressive by ALC and ANC. Infections experienced by CTCL patients did not increase in frequency with continued exposure to DD compared to placebo. DD does not further compromise immune function in CTCL patients. Median ALC and ANC for patients with MF PBO 9 μ g 18 μ g Cycle n ALC ANC n ALC ANC n ALC ANC Baseline 37 1.5 4.4 39 1.7 4.5 125 1.6 4.0 1 37 1.3 4.0 37 0.8 7.0 124 0.8 5.8 2 36 1.2 3.5 32 2.0 3.2 106 1.8 3.2 4 27 1.3 3.1 29 1.6 3.8 84 1.6 3.1 6 15 1.3 3.3 22 1.5 3.7 62 1.5 3.1 8 11 1.4 3.4 20 1.5 4.1 55 1.4 3.1 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai