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Drugs
Erschienen in: Drugs 6/2013

01.05.2013 | R&D Insight Report

Pomalidomide: First Global Approval

verfasst von: Shelley Elkinson, Paul L. McCormack

Erschienen in: Drugs | Ausgabe 6/2013

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Abstract

Pomalidomide (Pomalyst®) is a small molecule analogue of thalidomide under development with Celgene Corporation for the oral treatment of haematological and connective tissue diseases. Pomalidomide has been approved in the USA and is awaiting approval in the EU for use with low-dose dexamethasone for the treatment of relapsed and refractory multiple myeloma that has progressed following at least two prior therapies, including lenalidomide and bortezomib. The efficacy and safety of pomalidomide as monotherapy in patients with relapsed and refractory multiple myeloma has also been evaluated in a phase III trial. The agent is in phase III clinical development for the treatment of myelofibrosis and in phase II development for systemic sclerosis. Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom’s macroglobulinaemia. This article summarizes the milestones in the development of pomalidomide leading to this first global approval for relapsed and refractory multiple myeloma.
Literatur
1.
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.PubMedCrossRef
2.
Curran MP, McKeage K. Bortezomib: a review of its use in patients with multiple myeloma. Drugs. 2009;69(7):859–88.PubMedCrossRef
3.
Scott LJ, Lyseng-Williamson KA. Lenalidomide: a review of its use in the treatment of relapsed or refractory multiple myeloma. Drugs. 2011;71(5):625–49.PubMedCrossRef
4.
Plosker GL. Pegylated liposomal doxorubicin: a review of its use in the treatment of relapsed or refractory multiple myeloma. Drugs. 2008;68(17):2535–51.PubMedCrossRef
5.
Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565–71.PubMedCrossRef
6.
Payvandi F, Wu L, Haley M, et al. Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol. 2004;230(2):81–8.PubMedCrossRef
7.
Payvandi F, Wu L, Naziruddin SD, et al. Immunomodulatory drugs (IMiDs) increase the production of IL-2 from stimulated T cells by increasing PKC-theta activation and enhancing the DNA-binding activity of AP-1 but not NF-kappaB, OCT-1, or NF-AT. J Interferon Cytokine Res. 2005;25(10):604–16.PubMedCrossRef
8.
9.
10.
Richardson PG, Siegel DS, Vij R, et al. Randomized, open label phase 1/2 study of pomalidomide (POM) alone or in combination with low-dose dexamethasone (LoDex) in patients (Pts) with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide (LEN) and bortezomib (BORT): phase 2 results [abstract no. 634]. Blood. 2011;118(21).
11.
12.
13.
Andhavarapu S, Roy V. Immunomodulatory drugs in multiple myeloma. Expert Rev Hematol. 2013;6(1):69–82.PubMedCrossRef
14.
Ferguson GD, Jensen-Pergakes K, Wilkey C, et al. Immunomodulatory drug CC-4047 is a cell-type and stimulus-selective transcriptional inhibitor of cyclooxygenase 2. J Clin Immunol. 2007;27(2):210–20.PubMedCrossRef
15.
Gorgun G, Calabrese E, Soydan E, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010;116(17):3227–37.PubMedCrossRef
16.
Lentzsch S, LeBlanc R, Podar K, et al. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia. 2003;17(1):41–4.PubMedCrossRef
17.
Zhu YX, Braggio E, Shi C-X, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118(18):4771–9.PubMedCrossRef
18.
Giuliani N, Bolzoni M, Abeltino M, et al. CC-4047 (pomalidomide) inhibits multiple myeloma-induced osteoclast formation [abstract]. Haematologica. 2010;95:383.
19.
Anderson G, Gries M, Kurihara N, et al. Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood. 2006;107(8):3098–105.PubMedCrossRef
20.
Meiler SE, Wade M, Kutlar F, et al. Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. Blood. 2011;118(4):1109–12.PubMedCrossRef
21.
Moutouh-de Parseval LA, Verhelle D, Glezer E, et al. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest. 2008;118(1):248–58.
22.
Hoffmann M, Kasserra C, Reyes J, et al. Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration. Cancer Chemother Pharmacol. 2013;71(2):489–501.PubMedCrossRef
23.
Dimopoulos MA, Lacy MQ, Moreau P, et al. 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 [abstract no. LBA-6]. Blood. 2012;120(21).
24.
Jagannath S, Hofmeister CC, Siegel DS, et al. Pomalidomide (POM) with low-dose dexamethasone (LoDex) in patients (PTS) with relapsed and refractory multiple myeloma who have received prior therapy with lenalidomide (LEN) and bortezomib (BORT): updated phase 2 results and age subgroup analysis. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
25.
Lonial S, Baz R, Bahlis NJ, et al. Improvement in clinical benefit parameters with pomalidomide (POM) in combination with low-dose dexamethasone (LODEX) in patients with relapsed and refractory multiple myeloma (RRMM): results from a phase 2 study. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
26.
Richardson PG, Siegel D, Baz R, et al. A phase 1/2 multi-center, randomized, open label dose escalation study to determine the maximum tolerated dose, safety, and efficacy of pomalidomide alone or in combination with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide and bortezomib [abstract no. 864]. Blood. 2010;116(21).
27.
Lacy MQ, LaPlant BR, Laumann K, et al. Pomalidomide and dexamethasone in relapsed myeloma: results of 225 patients treated in five cohorts over three years. Blood Conference: 53rd Annual Meeting of the American Society of Hematology, ASH. 2011;118(21).
28.
Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009;27(30):5008–14.PubMedCrossRef
29.
Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010;24(11):1934–9.PubMedCrossRef
30.
Lacy MQ, Allred JB, Gertz MA, et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011;118(11):2970–5.PubMedCrossRef
31.
Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23(1):3–9.PubMedCrossRef
32.
Lacy MQ, Kumar SK, LaPlant BR, et al. Pomalidomide plus low-dose dexamethasone (pom/dex) in relapsed myeloma: Long term follow up and factors predicting outcome in 345 patients. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
33.
Short KD, Rajkumar SV, Larson D, et al. Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma. Leukemia. 2011;25(6):906–8.PubMedCrossRef
34.
Leleu X, Attal M, Arnuff B, et al. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. Blood. 2013.
35.
Streetly MJ, Gyertson K, Daniel Y, et al. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol. 2008;141(1):41–51.PubMedCrossRef
36.
Schey SA, Fields P, Bartlett JB, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol. 2004;22(16):3269–76.PubMedCrossRef
37.
Mark TM, Boyer A, Rossi AC, et al. ClaPD (clarithromycin, pomalidomide, dexamethasone) therapy in relapsed or refractory multiple myeloma. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
38.
Palumbo A, Larocca A, Montefusco V, et al. Pomalidomide cyclophosphamide and prednisone (PCP) treatment for relapsed/refractory multiple myeloma. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
39.
Richardson PG, Hofmeister CC, Siegel D, et al. MM-005: A phase 1, multicenter, open-label, dose-escalation study to determine the maximum tolerated dose for the combination of pomalidomide, bortezomib, and low-dose dexamethasone in subjects with relapsed or refractory multiple myeloma. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
40.
Shah JJ, Stadtmauer EA, Abonour R, et al. A multi-center phase I/II trial of carfilzomib and pomalidomide with dexamethasone (car-pom-D) in patients with relapsed/refractory multiple myeloma. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
41.
Baz R, Shain KH, Alsina M, et al. Oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone for relapsed and refractory myeloma: Report of the dose escalation cohort. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
42.
Tefferi A, Verstovsek S, Barosi G, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009;27(27):4563–9.PubMedCrossRef
43.
Begna KH, Mesa RA, Pardanani A, et al. A phase-2 trial of low-dose pomalidomide in myelofibrosis. Leukemia. 2011;25(2):301–4.PubMedCrossRef
44.
Mesa RA, Pardanani AD, Hussein K, et al. Phase1/-2 study of pomalidomide in myelofibrosis. Am J Hematol. 2010;85(2):129–30.PubMed
45.
Begna KH, Pardanani A, Mesa R, et al. Long-term outcome of pomalidomide therapy in myelofibrosis. Am J Hematol. 2012;87(1):66–8.PubMedCrossRef
46.
Amato RJ, Glode LM, Podolnick J, et al. Phase II study of pomalidomide in patients with castration-resistant prostate cancer. Cancers. 2011;3(3):3449–60.CrossRef
47.
Dispenzieri A, Buadi F, Laumann K, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012;119(23):5397–404.PubMedCrossRef
48.
Pusic I, DiPersio JF, Goran SL, et al. Phase-2 study of pomalidomide in advanced corticosteroid-resistant chronic graft-versus-host disease [abstract no. 3326]. Blood. 2009;114(22).
49.
Pusic I, DiPersio JF, Goran SL, et al. Pomalidomide (POM) in advanced corticosteroid-resistant chronic graft-versus-host disease (CGVHD). Biol Blood Marrow Transpl. 2010;16(2 SUPPL 2):S311.CrossRef
50.
Cooney MM, Nock C, Bokar J, et al. Phase I trial of pomalidomide given for patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012;70(5):755–61.PubMedCrossRef
51.
Infante JR, Jones SF, Bendell JC, et al. A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer. Eur J Cancer. 2011;47(2):199–205.PubMedCrossRef
52.
53.
Berenson JR, Hilger JD, Klein LM, et al. A phase 1/2 study of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed/refractory multiple myeloma. Blood Conference: 54th Annual Meeting of the American Society of Hematology, ASH. 2012;120(21).
Metadaten
Titel
Pomalidomide: First Global Approval
verfasst von
Shelley Elkinson
Paul L. McCormack
Publikationsdatum
01.05.2013
Verlag
Springer International Publishing AG
Erschienen in
Drugs / Ausgabe 6/2013
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-013-0047-x

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