Pharmacokinetic Evaluation Of Pomalidomide For The Treatment Of Myeloma
Francesca Gay, Roberto Mina, Rossella Troia, S Bringhen
Published 2013 · Medicine
Download PDFAnalyze on Scholarcy
Introduction: Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the immunomodulatory agent pomalidomide have provided new treatment strategies within the relapse setting. Pomalidomide, a novel 4-amino derived from thalidomide, was recently introduced for the treatment of MM. In addition to being immune-adjuvant with anti-inflammatory properties, pomalidomide has shown several biological activities that directly and indirectly inhibit MM cells. Areas covered: Herein, the authors review the chemistry, the mechanism of action and the pharmacokinetic properties of pomalidomide. The data reviewed within this article based on the relevant literature pertaining to pomalidomide's Phase I, II and III clinical trials. Expert opinion: Pomalidomide has shown to be a safe and active agent, both alone and in combination with dexamethasone, in heavily pretreated patients. Furthermore, pomalidomide represents an effective treatment option for relapsed/refractory patients. Results from the ongoing trials evaluating the synergistic activity of pomalidomide combined with conventional chemotherapy or novel agents look promising and may prove to be viable treatment options in the future.
This paper references
Review: extramedullary disease in multiple myeloma.
Sumit Madan (2009)
Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis.
Angela Dispenzieri (2012)
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
Jesús F San Miguel (2008)
Antonio Palumbo (2011)
European Myeloma Network . Thalidomide for previously untreated elderly patients with multiple myeloma : meta - analysis of 1685 individual patient data from 6 randomized clinical trials
PM Fayers (2012)
Phase III trial showing the superiority of pomalidomide plus low-dose dexamethasone over high-dose dexamethasone
Pomalidomide Cyclophosphamide and Prednisone is Active in Lenalidomide Relapsed/Refractory Multiple Myeloma
A Larocca (2013)
Pomalidomide in Combination with Low-Dose Dexamethasone: Demonstrates a Significant Progression Free Survival and Overall Survival Advantage, in Relapsed/Refractory MM: A Phase 3, Multicenter, Randomized, Open-Label Study
Meletios Athanasios Dimopoulos (2012)
Pomalidomide Plus Low-Dose Dexamethasone (POM+LoDEX) in RRMM: Analyses Based on Prior Therapy and Renal Function [abstract No: P-170
R Vij (2013)
Pomalidomide Plus Low-Dose Dexamethasone (POM+LoDEX) in RRMM: Analyses Based on Prior Therapy and Renal Function
Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Relapsed Myeloma: Long Term Follow up and Factors Predicing Outcome in 345 Patients
Martha Q Lacy (2012)
Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules.
Marina Bolzoni (2013)
Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications.
Nicholas Mitsiades (2002)
JR Berenson (2013)
Identification of a Primary Target of Thalidomide Teratogenicity
Takumi Ito (2010)
Extramedullary disease in multiple myeloma
Sumit Madan (2009)
Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib.
Paul G Richardson (2013)
Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of 225 Patients Treated in Five Cohorts Over Three Years,
Martha Q Lacy (2011)
A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma
Michel Attal (1996)
Pomalidomide and Dexamethasone (CPomd) for Relapsed/ Refractory Multiple Myleoma (RRMMM): A Phase I/II Trial
Cancer statistics, 2010.
Ahmedin Jemal (2010)
Biosynthesis and processing of cathepsin K in cultured human osteoclasts.
David J. Rieman (2001)
Improved survival in multiple myeloma and the impact of novel therapies.
Shaji K. Kumar (2008)
Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly.
Anita K. Gandhi (2006)
Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma.
Güllü T Görgün (2010)
Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma
Yuan Xiao Zhu (2013)
Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.
Laura G. Corral (1999)
Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide.
Yuan Xiao Zhu (2011)
Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma
Iris Breitkreutz (2008)
Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma.
Faith Davies (2001)
Immunomodulatory drugs in multiple myeloma: from molecular mechanisms of action to clinical practice
Roberto Castelli (2012)
Immunomodulatory drugs Revlimid® (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation
Dan Zhu (2008)
Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial.
Pieter Sonneveld (2012)
MM-008: A Phase 1 Trial Evaluating Pharmacokinetics and Tolerability Of Pomalidomide + Low-Dose Dexamethasone In Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment
Jeffrey V. Matous (2013)
Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study
Shaji K Kumar (2012)
Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02.
Xavier Leleu (2013)
Analysis of MM-003 Patients with Moderate Renal Impairment Using Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) vs. High-Dose Dexamethasone (HiDEX) in Relapsed/Refractory Multiple Myeloma (RRMM)
KC Weisel (2013)
Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial.
María-Victoria Mateos (2010)
Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials.
Peter Fayers (2011)
Ph 1 Trial of Pomalidomide, Bortezomib, and Low-dose Dexamethasone (PVD) in Relapsed and/or Refractory Multiple Myleoma
P G Richardson (2012)
Ph 1 Trial of Pomalidomide, Bortezomib, and Low-dose Dexamethasone (PVD) in Relapsed and/or Refractory Multiple Myleoma [abstract No: P-178
PG Richardson (2012)
High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma.
J. Anthony Child (2003)
Carfilzomib, Pomalidomide and Dexamethasone (CPomd) for Relapsed/ Refractory Multiple Myleoma (RRMMM): A Phase I/II Trial [abstract No: P-250
E Staudmauer (2013)
VISTA Trial Investigators bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma
JF San Miguel (2008)
Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation.
Matthew J Streetly (2008)
Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity.
George W. Muller (1996)
Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both Pomalidomide (PomalystR, Celgene) Expert Opin
D Zhu (2013)
Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy
Jake Shortt (2013)
Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial.
Sundararajan Vincent Rajkumar (2010)
Cereblon Expression Predicts Response, Progression Free and Overall Survival After Pomalidomide and Dexamethasone Therapy in Multiple Myeloma
Steven Robert Schuster (2012)
Oral Weekly Cyclophosphamide in Combination with Pomalidomide and Dexamethasone for Relapsed and Refractory Myeloma: Report of the Dose Escalation Cohort
Rachid Baz (2012)
Thalidomide and its analogues in the treatment of Multiple Myeloma
Tahir Latif (2012)
Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration
Matthew C. Hoffmann (2012)
Pomalidomide Cyclophosphamide and Prednisone is Active in Lenalidomide Relapsed/Refractory Multiple Myeloma [abstract No: O-5
A Larocca (2013)
Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.
Michel Attal (2012)
Continuous lenalidomide treatment for newly diagnosed multiple myeloma.
Antonio Palumbo (2012)
editors. SEER cancer statistics review, 1975-2007
SF Altekruse (2013)
Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma
Kristen E Detweiler Short (2011)
Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma.
Steve A. Schey (2004)
Pomalidomide+Pegylated Liposomal Doxorubicin in Relapsed/Refractory Multiple Myeloma
J R Berenson
Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.
Paul G Richardson (2014)
Lenalidomide after stem-cell transplantation for multiple myeloma.
Philip L McCarthy (2012)
Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study
Michele Cavo (2010)
This paper is referenced by
A Phase I, open-label, randomized, crossover study in healthy subjects to evaluate the bioavailability of, and the food effect on, a pomalidomide oral liquid suspension
Yan Li (2018)
Pharmacokinetics of Pomalidomide in a Patient Receiving Hemodialysis Using a High-Cutoff Filter.
Kim Dao (2017)
The role of P-glycoprotein in drug resistance in multiple myeloma
Joseph Abraham (2015)
Pomalidomide for the treatment of relapsed and refractory multiple myeloma
Anna Guidetti (2014)
Divisha Raheja (2015)
Plasma cell leukemia: update on biology and therapy
Roberto Mina (2017)
Pomalidomide in the management of relapsed multiple myeloma.
Cyrille Touzeau (2016)
An Open‐Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics
Yan Li (2019)
In Vivo Assessment of the Effect of CYP1A2 Inhibition and Induction on Pomalidomide Pharmacokinetics in Healthy Subjects
Yan Li (2018)
INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED GUIDELINE
GENERAL PRINCIPLES (2017)
Emerging Therapeutics for the Treatment of Light Chain and Transthyretin Amyloidosis
Kathleen W. Zhang (2019)