Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: An update for the hematologist

Therapeutic Advances in Hematology

Volumn 4, Issue 3, 2013, Pages 211-216

  Mccurdy, Arleigh R ^a   Lacy, Martha Q ^a  

^a MAYO CLINIC   (United States)

Author keywords

multiple myeloma; pomalidomide; treatment

Indexed keywords

ACETYLSALICYLIC ACID; BORTEZOMIB; CLARITHROMYCIN; DEXAMETHASONE; LENALIDOMIDE; MOLECULAR MARKER; POMALIDOMIDE; PROTEIN P53; THALIDOMIDE;

ANEMIA; AUTOLOGOUS STEM CELL TRANSPLANTATION; CELL CYCLE ARREST; CHEMICAL MODIFICATION; DRUG EFFICACY; DRUG MECHANISM; EVENT FREE SURVIVAL; FATIGUE; FOLLOW UP; GENE EXPRESSION PROFILING; HUMAN; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; THROMBOEMBOLISM; TREATMENT RESPONSE; TUMOR MICROENVIRONMENT; VENOUS THROMBOEMBOLISM;

EID: 84993710061     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620713480155     Document Type: Review

References (40)

1. Anderson G. Margarete G. Kurihara N. Honjo T. Anderson J. Donnenberg V. et al. (2006) Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood 107: 3098–3105.
2. Carrier M. Le Gal G. Tay J. Wu C. Lee A. (2011) Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thrombosis Haemostasis 9: 653–663.
3. Corral L. Haslett P. Muller G. Chen R. Wong L. Ocampo C. et al. (1999) Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 163: 380–386.
4. D'Amato R. Loughnan M. Flynn E. Folkman J. (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 91: 4082–4085.
5. Davies F. Raje N. Hideshima T. Lentzsch S. Young G. Tai Y. et al. (2001) Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 98: 210–216.
6. Dimopoulos M. Lacy M. Moreau P. Weisel K. Song K. Delforge M. et al. (2012) 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. In 54th ASH Annual Meeting and Exposition, Atlanta GA, 8–11 December 2012.
7. Dimopoulos M. Spencer A. Attal M. Prince H. Harousseau J. Dmoszynska A. et al. (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357: 2123–2132.
8. Escoubet-Lozach L. Lin I. Jensen-Pergakes K. Brady H. Gandhi A. Schafer P. et al. (2009) Pomalidomide and lenalidomide induce p 21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res 69: 7347–7356.
9. Ferguson G. Jensen-Pergakes K. Wilkey C. Jhaveri U. Richard N. Verhelle D. et al. (2007) Immunomodulatory drug CC-4047 is a cell-type and stimulus-selective transcriptional inhibitor of cyclooxygenase 2. J Clin Immunol 27: 210–220.
10. Gertz M. (2013) Pomalidomide and myeloma meningitis. Leukemia Lymphoma [ePub ahead of print].
11. Geyer H. Viggiano R. Lacy M. Witzig T. Leslie K. Mikhael J. et al. (2011) Acute lung toxicity related to pomalidomide. Chest 140: 529–533.
12. Haslett P. Corral L. Albert M. Kaplan G. (1998) Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 187: 885–1892.
13. Ito T. Ando H. Suzuki T. Ogura T. Hotta K. Imamura Y. (2010) Identification of a primary target of thalidomide teratogenicity. Science 327: 1345–1350.
14. Jagganath S. Hofmeister C. Siegel D. Vij R. Lonial S. Anderson K. et al. (2012) Pomalidomide with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma who have received prior therapy with lenalidomide and bortezomib: updated phase 2 results and age subgroup analysis. In 54th ASH Annual Meeting and Exposition, Atlanta GA, 8–11 December 2012.
15. Jemal A. Bray F. Center M. Ferlay J. Ward E. Forman D. (2011) Global cancer statistics. CA: Cancer J Clinicians 61 (2): 69–90.
16. Keifer J. Guttridge D. Ashburner B. Baldwin A. (2001) Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem 276: 22382–22387.
17. Kumar S. Crowley J. Lee J. Lahuerta J. Morgan G. Hoering A. et al. (2009) Natural history of multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter International Myeloma Working Group Study. In 51st ASH Annual Meeting and Exposition, New Orleans LA, 5–8 December 2009.
18. Kumar S. Rajkumar S. Dispezieri A. Lacy M. Hayman S. Buadi F. et al. (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111: 2516–2520.
19. Lacy M. Allred J. Gertz M. Hayman S. Detweiler Short K. Buadi F. et al. (2011) Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 118: 2970–2975.
20. Lacy M. Hayman S. Gertz M. Dispenzieri A. Buadi F. Kumar S. et al. (2009) Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol 27: 5008–5014.
21. Lacy M. Hayman S. Gertz M. Short K. Dispenzieri A. Kumar S. et al. (2010) Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia 24: 1934–1939.
22. Lacy M. Kumar S. LaPlant B. Laumann K. Gertz M. Hayman S. et al. (2012) Pomalidomide plus low-dose dexamethasone (pom/dex) in relapsed myeloma: long term follow up and factors predicting outcome in 345 patients. In 54th ASH Annual Meeting and Exposition, Atlanta GA, 8–11 December 2012.
23. Leleu X. Attal M. Arnulf B. Moreau P. Traulle C. Michalet M. et al. (2011) High response rates to pomalidomide and dexamethasone in patients with refractory myeloma, final analysis of IFM 2009–02. In 53rd ASH Annual Meeting and Exposition, San Diego CA, 10–13 December 2011.
24. Leleu X. Attal M. Moreau P. Duhamel A. Fernand J. Michalet M. et al. (2010) Phase 2 study of 2 modalities of pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. IFM 2009–02. In 52nd ASH Annual Meeting and Exposition, Orlando FL, 4–7 December 2010.
25. Lopez-Girona A. Mendy D. Ito T. Miller K. Gandhi A. Kang J. et al. (2012) Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia 26: 2326–2335.
26. Mark T. Boyer A. Rossi A. Shah M. Pearse R. Zafar F. et al. (2012) ClaPD (clarithromycin, pomalidomide, dexamethasone) therapy in relapsed or refractory multiple myeloma. In 54th ASH Annual Meeting and Exposition, Atlanta GA, 8–11 December 2012.
27. Mitsiades N. Mitsiades C. Poulaki V. Chauhan D. Richardson P. Hideshima T. et al. (2002) Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 99: 4525–4530.
28. Reddy N. Hernandez-Ilizaliturri F. Deeb G. Roth M. Vaughn M. Knight J. et al. (2008). Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol 140: 36–45.
29. Richardson P. Siegel D. Vij R. Hofmeister C. Jagannath S. Chen C. et al. (2011) 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. In 53rd ASH Annual Meeting and Exposition, San Diego CA, 10–13 December 2011.
30. Richardson P. Siegel D. Baz R. Kelley S. Munshi N. Laubach J. et al. (2012) Phase 1 study of pomalidomide MTD, safety and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood [ePub ahead of print].
31. Schey S. Fields P. Bartlett J. Clarke I. Ashan G. Knight R. et al. (2004) Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 22: 3269–3276.
32. Schuster S. Kortuem K. Zhu Y. Braggio E. Shi C. Bruins L. et al. (2012) Cereblon expression predicts response, progression free and overall survival after pomalidomide and dexamethasone therapy in multiple myeloma. In 54th ASH Annual Meeting and Exposition, Atlanta GA, 8–11 December 2012.
33. Short K. Rakjumar S. Larson D. Buadi F. Hayman S. Dispenziero A. et al. (2011) Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma. Leukemia 25: 906–908.
34. Siegel R. Naishadham D. Jemal A. (2012) Cancer statistics, 2012. CA: Cancer J Clinicians 62 (1): 10–29.
35. Singhal S. Mehta J. Desikan R. Ayers D. Roberson P. Eddlemon P. et al. (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341: 1565–1571.
36. Streetly M. Gyertson K. Daniel Y. Zeldis J. Kazmi M. Schey S. et al. (2008) Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol 141: 41–51.
37. von Lilienfeld-Toal M. Hahn-Ast C. Furkert K. Hoffman F. Naumann R. Bargou R. et al. (2008) A systematic review of phase II trials of thalidomide / dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur J Haematol 81: 247–252.
38. Weber D. Chen C. Niesvizky R. Wang M. Belch A. Stadmauer E. et al. (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357: 2133–2142.
39. Zhu Y. Braggio E. Chi C. Bruins L. Schmidt J. van Wier S. et al. (2011) Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood 118: 4771–4779.
40. Zhu Y. Kortuem K. Stewart A. (2012) Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leukemia Lymphoma [ePub ahead of print].