Carfilzomib and lenalidomide response related to VEGF and VEGFR2 germline polymorphisms.

The combination of carfilzomib, lenalidomide, and dexamethasone (CRd) has induced deep responses in patients with newly diagnosed multiple myeloma. While vascular endothelial growth factor (VEGF) pathway polymorphisms have been associated with clinical outcomes for antiangiogenesis agents, we explored associations between such polymorphisms and CRd clinical response. The VEGF-1498C>T (rs833061) and VEGFR2 V297I (rs2305948) were associated with CRd response (OR ≤ 0.10, P ≤ 0.009), whereas VEGF-1498C>T and VEGFR2 Q472H (rs1870377) were associated with minimum residual disease negativity (P ≤ 0.023). As these SNPs were not associated with disease parameters (e.g., plasma VEGF, albumin, or beta-2-microglobin concentration), data suggest these SNPs may be markers of CRd response.