DOI QR코드

DOI QR Code

Pooled Analysis of Pomalidomide for Treating Patients with Multiple Myeloma

  • Sun, Jia-Jia (The First Affiliated Hospital of Soochow University) ;
  • Zhang, Chi (The First Affiliated Hospital of Soochow University) ;
  • Zhou, Jun (The First Affiliated Hospital of Soochow University) ;
  • Yang, Hui-Lin (The First Affiliated Hospital of Soochow University)
  • Published : 2015.04.29

Abstract

Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is a new immunomodulatory drug with high in vitro potency. Immunomodulatory drugs are hypothesized to act through multiple mechanisms. Here we performed a systemic analysis to evaluate pomalidomide-based chemotherapy (pomalidomide in combination with low-dose dexamethasone) as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the efffectiveness of pomalidomide based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: For pomalidomide based regimens, 4 clinical studies which including 291 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 41.2% (120/291). Major adverse effects were hematologic toxicity, including grade 1 or 2 anemia, leucopenia and thrombocytopenia with pomalidomide based treatment. No treatment related death occurred. Conclusion: This pooled analysis suggests that pomalidomide in combination with low-dose dexamethasone is active with good tolerability in treating patients with refractory or relapsed multiple myeloma.

Keywords

Pomalidomide;multiple myeloma;treatment;prognosis

Acknowledgement

Supported by : Natural Science Foundation of China

References

  1. Cai X, Shen YL, Zhu Q, et al (2000). Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia. Leukemia, 14, 262-70. https://doi.org/10.1038/sj.leu.2401650
  2. Chen YC, Lin-Shiau SY, Lin JK (1998). Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J Cell Physiol, 177, 324-33. https://doi.org/10.1002/(SICI)1097-4652(199811)177:2<324::AID-JCP14>3.0.CO;2-9
  3. Corral LG, Haslett PA, Muller GW, 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, 380-6.
  4. Dalton WS (2002). Targeting the mitochondria : an exciting new approach to myeloma therapy. Commentary re: Bahlis NJ, et al. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res, 8, 3658-68.
  5. Davies FE, Raje N, Hideshima T, et al (2001). Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood, 98, 210-6. https://doi.org/10.1182/blood.V98.1.210
  6. Engelhardt M, Trepos E, Kleber M, et al (2014). European myeloma network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica, 92, 232-42.
  7. Fonseca R, Bergsagel PL, Drach J, et al (2009). International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia, 23, 2210-21. https://doi.org/10.1038/leu.2009.174
  8. Galustian C, Meyer B, Labarthe MC, et al (2009). The anticancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother, 58, 1033-45. https://doi.org/10.1007/s00262-008-0620-4
  9. Genadieva-Stavric S, Cavallo F, Palumbo A (2014). New approaches to management of multiple myeloma. Curr Treat Options Oncol, 15, 157-70. https://doi.org/10.1007/s11864-014-0276-6
  10. Jia P, Chen G, Huang X, et al (2001). Arsenic trioxide induces multiple myeloma cell apoptosis via disruption of mitochondrial transmembrane potentials and activation of caspase-3. Chin Med J (Engl), 114, 19-24.
  11. Hayashi T, Hideshima T, Akiyama M, et al (2005). Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol, 128, 192-203. https://doi.org/10.1111/j.1365-2141.2004.05286.x
  12. Hideshima T, Chauhan D, Schlossman R, et al (2001). The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene, 20, 4519-27. https://doi.org/10.1038/sj.onc.1204623
  13. Hideshima T, Chauhan D, Shima Y, et al (2000). Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood, 96, 2943-50.
  14. Jourdan M, Tarte K, Legouffe E, et al (1999). Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. Eur Cytokine Netw, 10, 65-70.
  15. Lacy MQ, Hayman SR, Gertz MA, et al (2010). Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia, 24, 1934-9. https://doi.org/10.1038/leu.2010.190
  16. Lacy MQ, Hayman SR, Gertz MA, et al (2009). Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol, 27, 5008-14. https://doi.org/10.1200/JCO.2009.23.6802
  17. Leleu X, Attal M, Arnulf B, et al (2013). Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma:Intergroupe Francophone du Myelome 2009-02. Blood, 121, 1968-75. https://doi.org/10.1182/blood-2012-09-452375
  18. Lin MG, Liu LP, Li CY, et al (2014). Scutellaria extract decreases the proportion of side population cells in a myeloma cell line by down-regulating the expression of ABCG2 protein. Asian Pac J Cancer Prev, 14, 7179-86.
  19. Lopez-Girona A, Mendy D, Ito T, et al (2012). Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia, 26, 2326-35. https://doi.org/10.1038/leu.2012.119
  20. Ludwig H, Beksac M, Blade J, et al (2011). Multiple myeloma treatment strategies with novel agents in 2011: a European perspective. The Oncologist, 16, 388-403. https://doi.org/10.1634/theoncologist.2010-0386
  21. Ocio EM, Fernandez-Lazaro D, San-Segundo L, et al (2011). Reversibility of the resistance to lenalidomide and pomalidomide and absence of cross-resistance in a murine model of MM Blood (ASH Annu Meet Abstr) (abstract 134).
  22. Palumbo A, Rajkumar V, San Miguel F, et al (2014). International Myeloma Working Group Consensus Statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol, 32, 587-600. https://doi.org/10.1200/JCO.2013.48.7934
  23. Pratt G (2002). Molecular aspects of multiple myeloma. Mol Pathol, 55, 273-83. https://doi.org/10.1136/mp.55.5.273
  24. Quach H, Ritchie D, Stewart AK, et al (2010). Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia, 24, 22-32. https://doi.org/10.1038/leu.2009.236
  25. Richardson PG, Siegel DS, Vij R, et al (2014). Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood, 123, 1826-32. https://doi.org/10.1182/blood-2013-11-538835
  26. Rollig C, Illmer T (2009). The efficacy of arsenic trioxide for the treatment of relapsed and refractory multiple myeloma:a systematic review. Cancer Treat Rev, 35, 425-30. https://doi.org/10.1016/j.ctrv.2009.04.007
  27. Rychak E, Mendy D, Miller K, et al (2011). Overcoming resistance; the use of pomalidomide (POM) and dexamethasone (DEX) in re-sensitizing lenalidomide (LEN)-resistant multiple myeloma (MM) cells Haematologica (EHA Annu Meet Abstr) (abstract P-328).
  28. Rychak E, Mendy D, Shi T, et al (2013). Pomalidomide and dexamethasone are synergistic in preclinical models of lenalidomide-refractory multiple myeloma (MM) Clin Lymphoma Myeloma Leuk (IMW Annu Meet Abstr) (Suppl 1)): abstract P-294.
  29. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  30. Stewart AK, Bergsagel PL, Greipp PR, et al (2007). A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia, 21, 529-34. https://doi.org/10.1038/sj.leu.2404516
  31. Weng WW, Dong MJ, Zhang J, et al (2014). A systematic review of MRI, scintigraphy, FDG-PET and PET/CT for diagnosis of multiple myeloma related bone disease--which is best? Asian Pac J Cancer Prev, 15, 9879-84. https://doi.org/10.7314/APJCP.2014.15.22.9879
  32. Zhang XZ, Su AL, Hu MQ, et al (2014). Elevated serum ferritin levels in patients with hematologic malignancies. Asian Pac J Cancer Prev, 15, 6099-101. https://doi.org/10.7314/APJCP.2014.15.15.6099
  33. Zheng H, Yang F (2014). Gemcitabine in treating patients with refractory or relapsed multiple myeloma. Asian Pac J Cancer Prev, 15, 9291-3. https://doi.org/10.7314/APJCP.2014.15.21.9291

Cited by

  1. Multiple Myeloma: a Retrospective Analysis of 61 Patients from a Tertiary Care Center vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.1833
  2. International Scoring System in Symptomatic Multiple Myeloma: Experience from a Tertiary Care Center vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.2031