An enigmatic case of primary refractory myeloma: Mystery solved

Inherited predisposition in myeloma has been anecdotally described with few reports in BRCA1/2, CDKN2A & mismatch repair deficiency. Hence, exact disease biology, response to standard therapy and outcomes are not clearly elucidated. This is attributed to less uptake of any genomic/genetic testing myeloma patients as the same is not mandated by international guidelines. A 53 year old male patient, diagnosed as primary refractory myeloma progressed on Dara-VRD. Owing to primary refractoriness, a repeat bone marrow aspirate was subjected to NGS both on CD138 selected plasma cells as well as the CD138 negative cells which revealed an MSH6 p. Y397C which was predicted to be VUS. IHC for MSH2 & MSH6 was employed on the biopsy which revealed a complete loss of MSH2 & MSH6 proteins.Currently he has received 4 cycles of PAD regimen and has achieved VGPR. This case underscores the importance of genomic testing especially in primary refractory cases.