Posted: Monday, April 3, 2023
For patients with multiple myeloma, dysregulation of the complement alternative pathway may increase their vulnerability to vascular endothelial injuries, according to a study published in Blood Cancer Journal. This dysregulation may also lead to carfilzomib-associated thrombotic microangiopathy and therefore warrants additional efforts to investigate the benefits of screening for complement mutations in this patient population, suggested Giada Bianchi, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
“Further studies are needed to fully elucidate the complex interplay of these genetic and environmental factors and to establish whether genetic testing for mutations in the complement inhibitory pathway may be helpful to better risk stratify and counsel multiple myeloma patients about the risk of thrombotic microangiopathy with carfilzomib treatment,” explained the study authors.
From 2005 to 2020, a total of 10 patients with multiple myeloma who developed thrombotic microangiopathy were recruited for the study and compared with 10 matched control patients with multiple myeloma without thrombotic microangiopathy. All patients were actively being treated with carfilzomib. Genomic DNA was obtained from all patients for complement pathway genetic testing, and the number of deletions indicated whether the patient had a normal test (no deletions), heterozygous gene deletion (one deletion), or homozygous gene deletion (two deletions).
The study revealed a 4.5-month median time to diagnosis of thrombotic microangiopathy from the commencement of carfilzomib therapy. In addition, deletion of the CFHR3::CFHR5 region was identified in 70% of cases, with two cases described as homozygous deletions. A total of 40% of patients had a CFHR3::CFHR1 heterozygous gene deletion, and 10% had a CFHR1::CFHR4 heterozygous gene deletion. Moreover, normal genomes were identified in two patients despite the presence of thrombotic microangiopathy. Furthermore, one patient had a mutation of the CFHR5 gene, with no evidence of deletion in the CFHR1::CFHR3 region. Within the control group, 30% had a heterozygous deletion of the CFHR1::CHFR3 region, with no evidence of thrombotic microangiopathy.
Disclosure: For full disclosures of the study authors, visit nature.com.