In the past, treatment for WHIM syndrome has focused on symptom management: treating infections and myelokathexis with antibiotics or granulocyte colony stimulating factor. Infusion can treat hypogammaglobulinemia and surgery can treat warts. But what if people living with this condition could have a therapy which encompassed treatment for all of the symptoms?
One potential therapy: mavorixafor. This investigational, orally available CXCR4 antagonist mobilizes white blood cells from the bone marrow into the blood; X4 Pharmaceuticals explains that this increases circulating neutrophil, lymphocyte, and monocyte levels to improve how your immune system functions.
X4 recently presented data from a Phase 3 clinical study evaluating mavorixafor for WHIM syndrome at the EHA 2023 Hybrid Congress. According to Jonathan Goodman of Hematology Advisor, 31 people aged 12 or older enrolled in the study. They were split into two cohorts: one of which received mavorixafor and the other which received a placebo. Their median absolute neutrophil counts were 150 and 200 cells/µL respectively. For context, a healthy individual has between 2,500 – 6,000 cells/µL. Learn more about absolute neutrophil count here.
Mavorixafor helped improve and maintain absolute neutrophil counts above threshold for 15.04 hours, compared to just 2.75 hours in the group receiving the placebo. Similarly, mavorixafor improved absolute lymphocyte count for 15.8 hours compared to just 4.55. The treatment was both safe and well-tolerated and reduced annualized infection rate significantly.
About WHIM Syndrome
WHIM syndrome—which stands for warts, hypogammaglobulinemia, infections, and myelokathexis—is a rare primary immunodeficiency disorder associated with CXCR4 gene mutations. These mutations make the CXCR4 protein overactive, leading to irregularities in the way cells develop and mature. Typically, WHIM syndrome is inherited in an autosomal dominant pattern, though the mutation occurs spontaneously with some people.
Symptoms related to WHIM syndrome can vary significantly between those affected. These symptoms often appear in infancy or early childhood. People with WHIM syndrome are more susceptible to recurrent and sometimes life-threatening bacterial infections, including skin infections, gum infections, sinusitis, middle ear infections, and bacterial pneumonia. Additional symptoms or characteristics can include:
- Hearing loss
- Tooth loss
- Bronchiectasis
- Warts (caused by HPV exposure) that can spread to the hands, feet, face, and trunk
- Mucosal, oral, or genital warts
- Increased risk of developing carcinoma
- Myelokathexis (too many white blood cells in the bone marrow)
- Hypogammaglobulinemia (low levels of certain antibodies)
