Carfilzomib and lenalidomide response related to VEGF and VEGFR2 germline polymorphisms

Tristan M. Sissung; Cody J. Peer; Neha Korde; Sham Mailankody; Dickran Kazandjian; David J. Venzon; Ola Landgren; William D. Figg

doi:10.1007/s00280-017-3323-8

Carfilzomib and lenalidomide response related to VEGF and VEGFR2 germline polymorphisms

Tristan M. Sissung, Cody J. Peer, Neha Korde, Sham Mailankody, Dickran Kazandjian, David J. Venzon, Ola Landgren, William D. Figg^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	217-221
Number of pages	5
Journal	Cancer Chemotherapy and Pharmacology
Volume	80
Issue number	1
DOIs	https://doi.org/10.1007/s00280-017-3323-8
State	Published - 1 Jul 2017
Externally published	Yes

Keywords

Carfilzomib
KDR
Lenalidomide
Multiple myeloma
Polymorphism
Vascular endothelial growth factor
Vascular endothelial growth factor receptor

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title = "Carfilzomib and lenalidomide response related to VEGF and VEGFR2 germline polymorphisms",

abstract = "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.",

keywords = "Carfilzomib, KDR, Lenalidomide, Multiple myeloma, Polymorphism, Vascular endothelial growth factor, Vascular endothelial growth factor receptor",

author = "Sissung, {Tristan M.} and Peer, {Cody J.} and Neha Korde and Sham Mailankody and Dickran Kazandjian and Venzon, {David J.} and Ola Landgren and Figg, {William D.}",

note = "Publisher Copyright: {\textcopyright} 2017, Springer-Verlag Berlin Heidelberg (outside the USA).",

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AU - Sissung, Tristan M.

AU - Peer, Cody J.

AU - Korde, Neha

AU - Mailankody, Sham

AU - Kazandjian, Dickran

AU - Venzon, David J.

AU - Landgren, Ola

AU - Figg, William D.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Carfilzomib

KW - KDR

KW - Lenalidomide

KW - Multiple myeloma

KW - Polymorphism

KW - Vascular endothelial growth factor

KW - Vascular endothelial growth factor receptor

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M3 - Article

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AN - SCOPUS:85019102334

SN - 0344-5704

VL - 80

SP - 217

EP - 221

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

IS - 1

ER -

Carfilzomib and lenalidomide response related to VEGF and VEGFR2 germline polymorphisms

Abstract

Keywords

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