A phase II clinical study of interleukin-11 mutein to treat patients with chemotherapy-induced thrombocytopenia.

Abstract

9113 Background: To demonstrate the safety and efficacy of genetically engineered human interleukin-11 mutein (mIL-11) on chemotherapy- induced thrombocytopenia (CIT) patients, a multicenter randomized controlled trial was conducted in China, comparing mIL-11 with the standard recombinant human interleukin-11 (rhIL-11, NEUMEGA) treatment in 83 cancer patients who had experienced platelet counts of ≤75,000/μL during the chemotherapy cycle immediately preceding study entry. Methods: Patients were randomized into either MR or RM group. Group MR represents the subcutaneous administration of mIL-11 (7.5 μ g/kg) once daily for 10 days beginning 72 hours after chemotherapy during a 21-day chemotherapy (cycle 1) followed by once daily subcutaneous administration of rhIL-11 in the clinical dose (25 μ g/kg) for 10 days (cycle 2). Group RM represents vice versa. In between cycle 1 and 2 for both groups, a 7-day wash-out period was assigned. Results: Intent-to-treat populations of mIL-11 (n=70) or rhIL-11 (n=76) were analyzed to evaluate the safety at all visits. Adverse events were mild or moderate, and the incidence of drug-related adverse events of mIL-11 (25.7%) were lower than those of rhIL-11 (40.8%) (p=0.07). None of Gr 3,4 unexpected adverse events nor death was observed during the study. In addition, no patients developed antibodies against the mIL-11 protein during the study. For the evaluation of efficacy, sixty patients were analyzed for their average platelet counts during the study. mIL-11 (7.5 μ g/kg) as well as rhIL- 11 (25 μ g/kg) were effective to increase the nadir platelet counts (62.58 ± 36.59 × 103/μL vs. 60.19 ± 32.09 × 103/μL for mIL-11 vs rhIL-11), as compared with the nontreated control group (40.98 ± 17.90 × 103/μ L) (p<0.0001). There was statistically no difference between mIL-11 and rhIL-11 for their efficacy, including average platelet counts (197.8 ± 123.6 × 103/μ L vs. 202.3 ± 118.9 × 103/μ L), and the platelet recovery rate during the study. Conclusions: mIL- 11 has equivalent thrombopoietic activity and is well tolerated at dose of 7.5 μg/kg, one-third dose of the clinical dose of rhIL-11 (25 μg/kg), suggesting the potential to reduce CIT in this model. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ViroMed Co., Ltd.