Study on Metformin in Fanconi Anemia

In a new study published in Blood Advances, it was shown that metformin is safe and tolerated in nondiabetic people with Fanconi anemia (FA) and may be helpful.

Fanconi anemia is a hereditary condition that affects DNA repair and is associated with bone marrow failure and cancer predisposition. Metformin, a biguanide metabolic drug, increases blood counts and slows tumor development in FA mice models. As a result, Jessica Pollard and colleagues undertook a single-institutional pilot trial of metformin in non-diabetic patients with FA to investigate the feasibility and tolerability of metformin treatment and to see if metformin may enhance blood counts.

In this trial, fourteen of fifteen patients with at least one cytopenia (hemoglobin 10g/dL, platelet count 100K cells/L, or absolute neutrophil count 1K cells/L) were suitable for metformin treatment for six months. The median patient age was 9.4 years (range 6.0-26.5), with 8/14 males (57%).

Key Findings

• Thirteen of fourteen individuals (93%) tolerated maximum age-appropriate doses; one subject had dose reduced due to grade 2 gastrointestinal problems.
• There were no cases of hypoglycemia or metabolic acidosis.
• There were no dosage interruptions owing to toxicity, and there were no grade 3 or higher adverse events associated with metformin.
• Four of the thirteen evaluable patients had a hematologic response (HR) based on modified MDS IWG criteria.
• The average time to respond was 84.5 days (range 71-128). Neutrophils (n=3), platelets (n=1), and red blood cells (n=1) all showed responses.
• During therapy, no patients satisfied the criteria for illness progression or relapse.
• Correlative research looked at the various mechanisms of metformin activity in FA.
• Metformin reduced inflammatory pathways in plasma proteomics.

In conclusion, Metformin may be a safe and acceptable treatment option in non-diabetic patients with FA, according to this study. Additional research is required to strengthen the current evidence.

Reference

Pollard, J., Furutani, E., Liu, S., Esrick, E. B., Cohen, L. E., Bledsoe, J. R., Liu, C.-W., Lu, K., Ramírez, M. J., Surrallés, J., Malsch, M. M., Kuniholm, A., Galvin, A., Armant, M., Kim, A. S., Ballotti, K., Moreau, L. A., Zhou, Y., Babushok, D. V., … Shimamura, A. (2022). Metformin for Treatment of Cytopenias in Children and Young Adults with Fanconi Anemia. In Blood Advances. American Society of Hematology. https://doi.org/10.1182/bloodadvances.2021006490