A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma

A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ?3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38-85), 5 (2-14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ?10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ?2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ?2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ?10 mg/kg

Variation in the Use of Ondansetron As An Antiemetic Drug in Children Treated With Chemotherapy

Selective 5-HT3 receptor antagonists such as ondansetron are potent antiemetics for chemotherapy-induced emesis. Ondansetron has been shown to be highly effective in preventing nausea and vomiting in children treated with chemotherapy and/or radiotherapy. However, its high cost may limit its application. A ''physician profile'' provided by the hospital pharmacy and a questionnaire survey conducted amongst the attending physicians of the hematology/oncology division of a children's hospital showed wide variation in ondansetron use. This variation was evident for both the indications of use and the schedule of administration. Moreover, 80% of the physicians were not aware of the actual cost of ondansetron. In order to reduce this variation, which may affect the quality of care and increase costs unnecessarily, guidelines have been developed for the use of antiemetic drugs in pediatric oncology patients at this institution. (C) 1995 Wiley-Liss, Inc