All Title Author
Keywords Abstract


Pulmonary Hypertension Induced by Thalidomide (and Derivatives) in Patients with Multiple Myeloma: A Systematic Review

DOI: 10.4236/jct.2016.713094, PP. 971-978

Keywords: Thalidomide, Thalidomide Derivatives, Pulmonary Hypertension, Multiple Myeloma

Full-Text   Cite this paper   Add to My Lib

Abstract:

Thalidomide is widely used in the treatment of multiple myeloma (MM). In recent years, several cases of pulmonary hypertension have been reported following treatment with thalidomide. The aim of this review was to evaluate the published literature on multiple myeloma patients with pulmonary hypertension following thalidomide treatment. A literature search was performed between 2000 and 2016. A total of 7 eligible studies were identified and deemed eligible, including 11 cases—approximately 37% (4 cases) with IgA (k), 27% (3 cases) with IgG (λ) MM, 27% (3 cases) with IgG (k) MM, and one case (9%) with primary plasma cell leukemia (PPCL). The vast majority of cases—82% (9 cases)—are associated with thalidomide, while only 18% (2 cases) are related to thalidomide derivatives (lenalidomide and pomalidomide). In conclusion, pulmonary hypertension induced by thalidomide or derivatives in multiple myeloma (MM) patients is related to a multifactorial etiology including the pathophysiology of the disease, thromboembolic events, preexisted cardiovascular conditions, comorbidities, and combination with other chemo- or bio-therapeutic agents. MM patients should be evaluated for signs and symptoms underlying cardiopulmonary disease before initiating, and during treatment with thalidomide.

References

[1]  McLaughlin, V.V. and McGoon, M.D. (2006) Pulmonary Arterial Hypertension. Circulation, 114, 1417-1431.
https://doi.org/10.1161/CIRCULATIONAHA.104.503540
[2]  Yuan, J.X.L. and Rubin, L.J. (2005) Pathogenesis of Pulmonary Arterial Hypertension: The Need for Multiple Hits. Circulation, 111, 534-538.
https://doi.org/10.1161/01.CIR.0000156326.48823.55
[3]  Egan, J.B., Shi, C.X., Tembe, W., Christoforides, A., Kurdoglu, A., Sinari, S., et al. (2012) Whole-Genome Sequencing of Multiple Myeloma from Diagnosis to Plasma Cell Leukemia Reveals Genomic Initiating Events, Evolution, and Clonal Tides. Blood, 120, 1060-1066.
https://doi.org/10.1182/blood-2012-01-405977
[4]  Van Marion, A.M., Auwerda, J.J.A., Lisman, T., Sonneveld, P., de Maat, M.P., Lokhorst, H.M., et al. (2008) Prospective Evaluation of Coagulopathy in Multiple Myeloma Patients before, during and after Various Chemotherapeutic Regimens. Leukemia Research, 32, 1078-1084.
https://doi.org/10.1016/j.leukres.2007.12.002
[5]  Auwerda, J.J.A., Sonneveld, P., de Maat, M.P. and Leebeek, F.W. (2007) Prothrombotic Coagulation Abnormalities in Patients with Newly Diagnosed Multiple Myeloma. Haematologica, 92, 279-280.
https://doi.org/10.3324/haematol.10454
[6]  Rajkumar, S.V., Blood, E., Vesole, D., Fonseca, R. and Greipp, P.R. (2006) Phase III Clinical Trial of Thalidomide plus Dexamethasone Compared with Dexamethasone alone in Newly Diagnosed Multiple Myeloma: A Clinical Trial Coordinated by the Eastern Cooperative Oncology Group. Journal of Clinical Oncology, 24, 431-436.
https://doi.org/10.1200/JCO.2005.03.0221
[7]  Rajkumar, S.V., Rosinol, L., Hussein, M., Catalano, J., Jedrzejczak, W., Lucy, L., et al. (2008) Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Thalidomide plus Dexamethasone Compared with Dexamethasone as Initial Therapy for Newly Diagnosed Multiple Myeloma. Journal of Clinical Oncology, 26, 2171-2177.
[8]  Hulin, C., Facon, T., Rodon, P., et al. (2009) Efficacy of Melphalan and Prednisone plus Thalidomide in Patients Older than 75 Years with Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial. Journal of Clinical Oncology, 27, 3664-3670.
https://doi.org/10.1200/JCO.2008.21.0948
[9]  Zervas, K., Mihou, D., Katodritou, E., Pouli, A., Mitsouli, C.H., Anagnostopoulos, A., et al. (2007) VAD-Doxil versus VAD-Doxil plus Thalidomide as Initial Treatment for Multiple Myeloma: Results of a Multicenter Randomized Trial of the Greek Myeloma Study Group. Annals of Oncology, 18, 1369-1375.
https://doi.org/10.1093/annonc/mdm178
[10]  Palumbo, A., Bringhen, S., Liberati, A.M., Caravita, T., Falcone, A., Callea, V., et al. (2008) Oral Melphalan, Prednisone, and Thalidomide in Elderly Patients with Multiple Myeloma: Updated Results of a Randomized Controlled Trial. Blood, 112, 3107-3114.
https://doi.org/10.1182/blood-2008-04-149427
[11]  Glasmacher, A., Hahn, C., Hoffmann, F., Naumann, R., Goldschmidt, H., Lilienfeld-Toal, M., et al. (2006) A Systematic Review of Phase-II Trials of Thalidomide Monotherapy in Patients with Relapsed or Refractory Multiple Myeloma. British Journal of Haematology, 132, 584-593.
https://doi.org/10.1111/j.1365-2141.2005.05914.x
[12]  Prince, H.M., Schenkel, B. and Mileshkin, L. (2007) An Analysis of Clinical Trials Assessing the Efficacy and Safety of Single-Agent Thalidomide in Patients with Relapsed or Refractory Multiple Myeloma. Leukemia & Lymphoma, 48, 46-55.
https://doi.org/10.1080/10428190601001904
[13]  Morgan, G.J., Gregory, W.M., Davies, F.E., Bell, S.E., Szubert, A.J., Brown, J.M., et al. (2012) The Role of Maintenance Thalidomide Therapy in Multiple Myeloma: MRC Myeloma IX Results and Meta-Analysis. Blood, 119, 7-15.
https://doi.org/10.1182/blood-2011-06-357038
[14]  Holstein, S.A., Tong, H. and Hohl, R.J. (2010) Differential Activities of Thalidomide and Isoprenoid Biosynthetic Pathway Inhibitors in Multiple Myeloma Cells. Leukemia Research, 34, 344-351.
https://doi.org/10.1016/j.leukres.2009.06.035
[15]  Hideshima, T., Chauhan, D., Shima, Y., Raje, N., Davies, F.E., Tai, Y.T., et al. (2000) Thalidomide and Its Analogs Overcome Drug Resistance of Human Multiple Myeloma Cells to Conventional Therapy. Blood, 96, 2943-2950.
[16]  Bartlett, J.B., Dredge, K. and Dalgleish, A.G. (2004) The Evolution of Thalidomide and Its IMiD Derivatives as Anticancer Agents. Nature Reviews Cancer, 4, 314-322.
https://doi.org/10.1038/nrc1323
[17]  Hayashi, T., Hideshima, T., Akiyama, M., Podar, K., Yasui, H., Raje, N., et al. (2005) Molecular Mechanisms Whereby Immunomodulatory Drugs Activate Natural Killer Cells: Clinical Application. British Journal of Haematology, 128, 192-203.
https://doi.org/10.1111/j.1365-2141.2004.05286.x
[18]  Cavo, M.I., Zamagni, E., Tosi, P., Cellini, C., Cangini, D., Tacchetti, P.A., et al. (2004) First-Line Therapy with Thalidomide and Dexamethasone in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma. Haematologica, 89, 826-831.
[19]  Hussein, M.A. (2006) Thromboembolism Risk Reduction in Multiple Myeloma Patients Treated with Immunomodulatory Drug Combinations. Thrombosis and Haemostasis, 95, 917-1051.
https://doi.org/10.1160/th06-02-0080
[20]  Farber, H.W. and Loscaizo, J. (2004) Pulmonary Arterial Hypertension. New England Journal of Medicine, 351, 1655-1665.
https://doi.org/10.1056/NEJMra035488
[21]  Hoeper, M.M., Bogaard, H.J., Condliffe, R., Frantz, R., Khanna, D., Kurzyna, M., et al. (2013) Definitions and Diagnosis of Pulmonary Hypertension. Journal of the American College of Cardiology, 62, D42-D50.
https://doi.org/10.1016/j.jacc.2013.10.032
[22]  Simonneau, G., Gatzoulis, M.A., Adatia, I., Celermajer, D., Denton, C., Ghofrani, A., et al. (2013) Updated Clinical Classification of Pulmonary Hypertension. Journal of the American College of Cardiology, 62, D34-D41.
https://doi.org/10.1016/j.jacc.2013.10.029
[23]  Lafaras, C., Mandala, E., Verrou, E., Platogiannis, D., Barbetakis, N., Bischiniotis, T., et al. (2008) Non-Thromboembolic Pulmonary Hypertension in Multiple Myeloma, after Thalidomide Treatment: A Pilot Study. Annals of Oncology, 19, 1765-1769.
https://doi.org/10.1093/annonc/mdn287
[24]  Hurtado, G.R. and García, R.M. (2013) [Pulmonary Hypertension in a Patient with Talidomide]. Farmacia hospitalaria: organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria, 37, 267-269. (In Spanish)
[25]  International Myeloma Working Group (2003) Criteria for the Classification of Monoclonal Gammopathies, Multiple Myeloma and Related Disorders: A Report of the International Myeloma Working Group. British Journal of Haematology, 121, 749-757.
[26]  Younis, T.H. (2003) Reversible Pulmonary Hypertension and Thalidomide Therapy for Multiple Myeloma. British Journal of Haematology, 121, 191-192.
https://doi.org/10.1046/j.1365-2141.2003.04245_2.x
[27]  Hattori, Y., Shimoda, M., Okamoto, S., Satoh, T., Kakimoto, T. and Ikeda, Y. (2005) Pulmonary Hypertension and Thalidomide Therapy in Multiple Myeloma. British Journal of Haematology, 128, 885-887.
https://doi.org/10.1111/j.1365-2141.2005.05389.x
[28]  Antonioli, E., Nozzoli, C., Gianfaldoni, G., Mannelli, F., Rossi, S., Betti, S., et al. (2005) Pulmonary Hypertension Related to Thalidomide Therapy in Refractory Multiple Myeloma. Annals of Oncology, 16, 1849-1850.
https://doi.org/10.1093/annonc/mdi357
[29]  Villa, A., Mazzola, A.A., Ghio, S., Martinoli, E. and Marino, P. (2011) Reversible Pulmonary Hypertension Related to Thalidomide Treatment for Multiple Myeloma. Case Reports in Oncology, 4, 487-489.
https://doi.org/10.1159/000333016
[30]  Tamura, S., Koyama, A., Shiotani, C., Kurihara, T., Nishikawa, A., Okamoto, Y., et al. (2014) Successful Bortezomib/Dexamethasone Induction Therapy with Lenalidomide in an Elderly Patient with Primary Plasma Cell Leukemia Complicated by Renal Failure and Pulmonary Hypertension. Internal Medicine, 53, 1171-1175.
https://doi.org/10.2169/internalmedicine.53.1672
[31]  Krishnan, U., Mark, T.M., Niesvizky, R. and Sobol, I. (2015) Pulmonary Hypertension Complicating Multiple Myeloma. Pulmonary Circulation, 5, 590-597.
https://doi.org/10.1086/682430

Full-Text

comments powered by Disqus