Arterial Thromboembolism Risk Identified in Multiple Myeloma

ARTERIAL thromboembolism (ATE) occurred in 92 of 4,287 patients with newly diagnosed multiple myeloma (MM) receiving immunomodulatory drug (IMiD) based induction, according to findings from the Myeloma-XI trial. The study examined the incidence, timing and clinical and genetic factors associated with ATE across different treatment phases. 

All patients received IMiD based induction, while 1,412 were randomised to lenalidomide maintenance. The researchers also examined tumour and inherited genetic factors in separate subsets of 1,800 patients each. Inherited genetic associations were investigated using a genome-wide association study (GWAS). 

ATE occurred in 92 patients, 2.1% of the overall study population, and was predominantly ischaemic stroke, accounting for more than 80% of events. 

Clinical And Tumour Factors Identified 

At MM diagnosis, higher leucocyte count, lower serum albumin and lenalidomide based induction among older patients were independently associated with ATE risk. During maintenance treatment, older age was the predominant determinant of ATE. 

The analysis also identified an association between tumour genetics and ATE. Deletion of chromosome 17p, known as del(17p), was strongly associated with increased ATE risk: hazard ratio (HR): 3.5; p=0.001. 

The findings therefore indicated that factors associated with ATE risk varied according to the treatment phase. Clinical characteristics were associated with risk around MM diagnosis, while older age was particularly relevant during maintenance treatment. 

Genetic Association Warrants Validation 

The GWAS identified a germline locus at 6q15 that was independently associated with ATE risk: odds ratio (OR): 4.8; p=3.9×10−8. Functional annotation implicated vascular enhancer activity and regulation of MAP3K7 and BACH2. 

The researchers noted that the findings were hypothesis generating and require validation in independent cohorts. The results suggested that inherited genetic variation may contribute to individual susceptibility to ATE among patients receiving IMiD based treatment. 

Future validation could clarify whether clinical and genetic factors can contribute to individualised approaches to ATE prevention. The findings also highlighted distinct patterns of ATE risk across induction and maintenance phases of treatment. 

Reference 

Beer SA et al. Clinical, cytogenetic, and germline genetic determinants of arterial thromboembolism in IMiD-treated multiple myeloma. Blood Cancer J. 2026;DOI: https://doi.org/10.1038/s41408-026-01635-3.