Julia Warren, MD, Ph.D., Associate Professor of Hematology at the University of Pennsylvania and Hematologist at Children’s Hospital of Philadelphia, discusses the results of a phase 1b trial evaluating mavorixafor across patients with chronic neutropenic disorders.
Chronic neutropenic disorders are blood disorders characterized by low levels of neutrophils. These disorders are associated with an increased risk of recurrent and/or severe infections. The most common chronic neutropenic disorders are chronic idiopathic neutropenia, cyclic neutropenia, and severe congenital neutropenia (SCN). The current management strategy for chronic neutropenia is long-term treatment with injectable granulocyte colony-stimulating factor (G-CSF).
As Dr. Warren explains, mavorixafor is an oral antagonist of the CXCR4 receptor in clinical development for the treatment of patients with multiple chronic neutropenic disorders. At the most recent American Society of Hematology Meeting & Exposition (ASH 2022), results were presented from the phase 1b, open-label, multicenter trial evaluating the safety and tolerability of mavorixafor use across several chronic neutropenic disorders. This study also serves as a proof of concept for the efficacy of mavorixafor use in patients with chronic neutropenia.
Study:
Patients received ≥1 dose of mavorixafor (≤50 kg, 200 mg; >50 kg, 400 mg), regardless of whether they were receiving current G-CSF treatment. Patients were monitored for hematologic parameters over the course of 6 to 8 hours 1 day before receiving mavorixafor (day -1) and on the first day of mavorixafor treatment (day 1), and were followed for 30 days for safety and tolerability.
As of June 2022, 15 patients were enrolled and dosed. Overall, meaningful increases in absolute neutrophil count and all other hematologic parameters evaluated were observed on day 1 in all patients treated with ≥1 dose of mavorixafor regardless of concurrent G-CSF use or type of chronic neutropenia.
The mean maximum fold change in absolute neutrophil count from day -1 to day 1 across all included patients was 4.72 at peak over the course of 6 to 8 hours after dose 1. The mean maximum fold change in other hematologic parameters, including total white blood cell count, absolute lymphocyte count, and absolute monocyte count, from day -1 to day 1 was 3.14, 3.05, and 2.64, respectively. For patients on G-CSF at day -1, the mean maximum fold change in total white blood cell count, absolute neutrophil count, absolute lymphocyte count, and absolute monocyte count from day -1 to day 1 was 2.87, 3.67, 3.07, and 2.44, respectively. For patients not on G-CSF, the mean maximum fold change in total white blood cell count, absolute neutrophil count, absolute lymphocyte count, and absolute monocyte count from day -1 to day 1 was 3.54, 6.28, 3.01, and 2.95, respectively.
Mavorixafor treatment was well tolerated overall. Treatment-emergent adverse events (n=11) were all grade 1; no serious treatment-emergent adverse events were reported.
To learn more about chronic neutropenic disorders and other rare hematological disorders, visit https://checkrare.com/diseases/hematologic-disorders/