Abstract
Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered incurable using the currently available treatments. Cytogenetic, molecular and proteonomic techniques have contributed toward a better understanding of the pathophysiology and prognostic factors of this heterogeneous malignancy, whose management has rapidly evolved over the years. The introduction of thalidomide, and the development of safer and more effective thalidomide analogues, represents the major therapeutic advances. Thalidomide, initially used in the treatment of MM because of its angiogenic properties, has considerable therapeutic activity (alone or in combination with other drugs) at all stages of the disease. However, a number of new analogues, such as lenalidomide and pomalidomide, have been developed and are known as "immunomodulatory drugs" (IMIDs). Although they are analogues of thalidomide, they have direct anti-tumor properties, a better tolerability profile and specific activity in both relapsing refractory MM and newly diagnosed disease. The mechanisms of action of IMIDs are still being investigated, but recent studies suggest that, in addition to their anti-angiogenic activity, they have anti-inflammatory and immunomodulatory properties, and directly and indirectly target tumor activity by interfering with various components of the bone marrow (BM) micro-environment. In this paper, we review the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and the current status of IMIDs in the treatment of MM.
| Original language | English |
|---|---|
| Pages (from-to) | 740-753 |
| Number of pages | 14 |
| Journal | Immunopharmacology and Immunotoxicology |
| Volume | 34 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Oct 2012 |
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Keywords
- Immunomodulatory drugs (IMIDs)
- Immunomodulatory effects
- Lenalidomide
- Multiple myeloma
- Pomalidomide
- Thalidomide
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Pharmacology
- Toxicology
Cite this
Immunomodulatory drugs in multiple myeloma : From molecular mechanisms of action to clinical practice. / Castelli, Roberto; Cannavò, Antonino; Conforti, Fabio; Grava, Giovanni; Cortelezzi, Agostino.
In: Immunopharmacology and Immunotoxicology, Vol. 34, No. 5, 10.2012, p. 740-753.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunomodulatory drugs in multiple myeloma
T2 - From molecular mechanisms of action to clinical practice
AU - Castelli, Roberto
AU - Cannavò, Antonino
AU - Conforti, Fabio
AU - Grava, Giovanni
AU - Cortelezzi, Agostino
PY - 2012/10
Y1 - 2012/10
N2 - Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered incurable using the currently available treatments. Cytogenetic, molecular and proteonomic techniques have contributed toward a better understanding of the pathophysiology and prognostic factors of this heterogeneous malignancy, whose management has rapidly evolved over the years. The introduction of thalidomide, and the development of safer and more effective thalidomide analogues, represents the major therapeutic advances. Thalidomide, initially used in the treatment of MM because of its angiogenic properties, has considerable therapeutic activity (alone or in combination with other drugs) at all stages of the disease. However, a number of new analogues, such as lenalidomide and pomalidomide, have been developed and are known as "immunomodulatory drugs" (IMIDs). Although they are analogues of thalidomide, they have direct anti-tumor properties, a better tolerability profile and specific activity in both relapsing refractory MM and newly diagnosed disease. The mechanisms of action of IMIDs are still being investigated, but recent studies suggest that, in addition to their anti-angiogenic activity, they have anti-inflammatory and immunomodulatory properties, and directly and indirectly target tumor activity by interfering with various components of the bone marrow (BM) micro-environment. In this paper, we review the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and the current status of IMIDs in the treatment of MM.
AB - Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered incurable using the currently available treatments. Cytogenetic, molecular and proteonomic techniques have contributed toward a better understanding of the pathophysiology and prognostic factors of this heterogeneous malignancy, whose management has rapidly evolved over the years. The introduction of thalidomide, and the development of safer and more effective thalidomide analogues, represents the major therapeutic advances. Thalidomide, initially used in the treatment of MM because of its angiogenic properties, has considerable therapeutic activity (alone or in combination with other drugs) at all stages of the disease. However, a number of new analogues, such as lenalidomide and pomalidomide, have been developed and are known as "immunomodulatory drugs" (IMIDs). Although they are analogues of thalidomide, they have direct anti-tumor properties, a better tolerability profile and specific activity in both relapsing refractory MM and newly diagnosed disease. The mechanisms of action of IMIDs are still being investigated, but recent studies suggest that, in addition to their anti-angiogenic activity, they have anti-inflammatory and immunomodulatory properties, and directly and indirectly target tumor activity by interfering with various components of the bone marrow (BM) micro-environment. In this paper, we review the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and the current status of IMIDs in the treatment of MM.
KW - Immunomodulatory drugs (IMIDs)
KW - Immunomodulatory effects
KW - Lenalidomide
KW - Multiple myeloma
KW - Pomalidomide
KW - Thalidomide
UR - http://www.scopus.com/inward/record.url?scp=84866241084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866241084&partnerID=8YFLogxK
U2 - 10.3109/08923973.2012.658921
DO - 10.3109/08923973.2012.658921
M3 - Article
C2 - 22401643
AN - SCOPUS:84866241084
VL - 34
SP - 740
EP - 753
JO - Immunopharmacology and Immunotoxicology
JF - Immunopharmacology and Immunotoxicology
SN - 0892-3973
IS - 5
ER -