(PA-223) GPRC5D and BCMA Genotypes in Relation to Diagnosis, Prognosis and Lenalidomide-based Maintenance Therapy in Multiple Myeloma Patients

Multiple myeloma (MM) is an incurable plasma cell malignancy, with prognosis prediction and treatment personalization remaining key challenges. This study explores germline genetic variability in MM patients to improve risk stratification, focusing on BCMA and GPRC5D genes that encode for two plasma cell surface proteins relevant for MM biology and targeted therapies.

Methods: We genotyped polymorphisms of these genes in 305 MM patients and correlated them with MM risk, disease progression, treatment response, and overall survival.

Results: Among the SNPs evaluated, rs3850997 in the BCMA gene was significantly associated with progression-free survival. Among patients not receiving maintenance therapy, T allele carriers exhibited prolonged PFS (HR = 0.65, 95% CI: 0.35–0.88, p = 0.013). When patients undergoing maintenance therapy were included, the benefit of maintenance appeared limited to those with the G/G genotype, whereas T allele carriers did not derive additional advantage, suggesting a genotype-specific modulation of therapy effectiveness.

Conclusions: Given the role of BCMA and GPRC5D in plasma cell function and emerging targeted therapies, further research is needed to validate their clinical utility in personalized treatment strategies.