PORTLAND, OregonA phase III study presented at the ASH meeting shows that oprel-vekin (rhIL-11, Neumega) effectively prevents severe chemotherapy-induced thrombocytopenia. Additional benefits included accelerated neutrophil recovery and fewer cases of neutropenic fever.
John W. Smith II, MD, chief of clinical research, Earle A. Chiles Research Institute, Portland, Oregon, presented the findings of this multicenter trial. Planned accrual was 250 patients, but the study was closed when the FDA approved Neumega based on previous trials. Still, 141 patients with solid tumors or lymphoma who were receiving various chemotherapy regimens were entered into the study, which is the largest randomized trial of the drug to date.
Eligible patients had a platelet nadir of less than 25,000/mm³ during the cycle before study entry and continued at the same chemotherapy doses for the study duration; 133 randomized patients received at least one dose of Neumega or placebo. G-CSF was allowed. Platelet transfusion was recommended at counts below 20,000/mm³, but was left to the discretion of the attending.
Patients received their chemotherapy without dose reduction for up to 5 days and then started treatment the next day with placebo or Neumega (50 µg/kg SC) for up to 14 days or until platelets were more than 100,000/mm³ after the expected nadir.
The study found that Neumega patients had higher platelet nadirs and were less likely than placebo patients to be given platelet transfusions. Twice as many Neumega patients as placebo patients were platelet-transfusion free with a platelet nadir above 20,000/mm3 (35% vs 18%, P = .04); 10,000/mm3 (45% vs 20%, P = .004); and any nadir (48% vs 22%).
Among the 88 Neumega patients, the mean number of platelet transfusions was 1.6 vs 2.2 for placebo (P = .01). There was no difference in the time to platelet recovery (50,000 or 100,000/mm³) between the groups.
Overall, the study corroborated the pivotal study that led to FDA approval of the agent. Neumega was highly effective in preventing severe thrombocytopenia with a reasonable safety profile. Most adverse events were mild-to-moderate and reversible, Dr. Smith said. Only 13% of patients stopped treatment because of adverse events.
The study also found that Neumega stimulated myeloid recovery. The median duration of neutropenia was 1 day for Neumega patients vs 3 days for placebo, and the incidence of neutropenic fever was reduced (14% vs 29%).