Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma

H. Quach; D. Ritchie; A. K. Stewart; P. Neeson; S. Harrison; M. J. Smyth; H. M. Prince

doi:10.1038/leu.2009.236

Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma

H. Quach, D. Ritchie, A. K. Stewart, P. Neeson, S. Harrison, M. J. Smyth, H. M. Prince

Hematology/Oncology

Research output: Contribution to journal › Review article › peer-review

362 Scopus citations

Abstract

Immunomodulatory drugs (IMiDs) are thalidomide analogues, which possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and anti-proliferative effects. Their development was facilitated by an improved understanding in myeloma (MM) biology and initiated a profound shift in the therapeutic approach towards MM. Despite the diverse effects of IMiDs in vitro, the relative contribution of each effect towards their ultimate anti-MM activity is still unclear. Based on in vitro data, it appears that anti-proliferative effects and downregulation of crucial cytokines are their most important anti-MM attributes. Although the co-stimulatory effects on T and NK cells have been heralded as a unique and important property of IMiDs towards enhancing anti-MM immune activity, these in vitro effects have yet to be firmly corroborated in vivo. Much is yet to be elucidated regarding the complex interplay of immunomodulatory cytokines that occurs in vivo, which ultimately dictates the net effects of IMiDs in MMthe understanding of which is necessary to facilitate optimal manipulation of these drugs in future MM management.

Original language	English (US)
Pages (from-to)	22-32
Number of pages	11
Journal	Leukemia
Volume	24
Issue number	1
DOIs	https://doi.org/10.1038/leu.2009.236
State	Published - Jan 2010

Keywords

IMiDs
Immunomodulatory
Lenalidomide
Myeloma

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/leu.2009.236

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title = "Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma",

abstract = "Immunomodulatory drugs (IMiDs) are thalidomide analogues, which possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and anti-proliferative effects. Their development was facilitated by an improved understanding in myeloma (MM) biology and initiated a profound shift in the therapeutic approach towards MM. Despite the diverse effects of IMiDs in vitro, the relative contribution of each effect towards their ultimate anti-MM activity is still unclear. Based on in vitro data, it appears that anti-proliferative effects and downregulation of crucial cytokines are their most important anti-MM attributes. Although the co-stimulatory effects on T and NK cells have been heralded as a unique and important property of IMiDs towards enhancing anti-MM immune activity, these in vitro effects have yet to be firmly corroborated in vivo. Much is yet to be elucidated regarding the complex interplay of immunomodulatory cytokines that occurs in vivo, which ultimately dictates the net effects of IMiDs in MMthe understanding of which is necessary to facilitate optimal manipulation of these drugs in future MM management.",

keywords = "IMiDs, Immunomodulatory, Lenalidomide, Myeloma",

author = "H. Quach and D. Ritchie and Stewart, {A. K.} and P. Neeson and S. Harrison and Smyth, {M. J.} and Prince, {H. M.}",

note = "Funding Information: Drs Hang Quach, Paul Neeson and Mark J Smyth declare no potential conflict of interest. Professors H Miles Prince and A Keith Stewart have both participated in advisory boards and received research funding from Celgene Corporation. Dr Simon Harrison has received research funding from Celgene Corporation. Funding Information: We acknowledge the insightful comments and critical review of the article by A/Prof S Opat, P Schafer, and Dr H Tran. Dr Hang Quach received funding support from the Vincent Fairfax Scholarship (Royal Australasian College of Physicians), and the Peter MacCallum Foundation (Morris Family Grant).",

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AU - Neeson, P.

AU - Harrison, S.

AU - Smyth, M. J.

AU - Prince, H. M.

N1 - Funding Information: Drs Hang Quach, Paul Neeson and Mark J Smyth declare no potential conflict of interest. Professors H Miles Prince and A Keith Stewart have both participated in advisory boards and received research funding from Celgene Corporation. Dr Simon Harrison has received research funding from Celgene Corporation. Funding Information: We acknowledge the insightful comments and critical review of the article by A/Prof S Opat, P Schafer, and Dr H Tran. Dr Hang Quach received funding support from the Vincent Fairfax Scholarship (Royal Australasian College of Physicians), and the Peter MacCallum Foundation (Morris Family Grant).

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N2 - Immunomodulatory drugs (IMiDs) are thalidomide analogues, which possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and anti-proliferative effects. Their development was facilitated by an improved understanding in myeloma (MM) biology and initiated a profound shift in the therapeutic approach towards MM. Despite the diverse effects of IMiDs in vitro, the relative contribution of each effect towards their ultimate anti-MM activity is still unclear. Based on in vitro data, it appears that anti-proliferative effects and downregulation of crucial cytokines are their most important anti-MM attributes. Although the co-stimulatory effects on T and NK cells have been heralded as a unique and important property of IMiDs towards enhancing anti-MM immune activity, these in vitro effects have yet to be firmly corroborated in vivo. Much is yet to be elucidated regarding the complex interplay of immunomodulatory cytokines that occurs in vivo, which ultimately dictates the net effects of IMiDs in MMthe understanding of which is necessary to facilitate optimal manipulation of these drugs in future MM management.

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Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma

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