Low incidence of thromboembolism in multiple myeloma patients receiving immunomodulatory drugs; a retrospective single-institution analysis
- 30 Downloads
Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30–85 years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184 days (range 21–2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3 years. Multivariate analysis determined that age > 70 years (p = 0.012) and BMI < 18.5 kg/m2 (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings.
KeywordsMultiple myeloma Thromboembolism Anticoagulants Hemorrhage Risk assessment
KT, ST, and ES designed the study. KT enrolled the patients and collected the data. KT, ST, CO, and YK performed the statistical analysis. KT and ST wrote the paper. All authors reviewed and edited the manuscript, which was exclusively and critically revised by CN and ES.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This retrospective study was approved by the Ethics Committee of Chiba University School of Medicine. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Research involving animal studies
This article does not contain any studies with animals performed by any of the authors.
- 2.Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, Harousseau J, Zonder JA, Cavo M, Zangari M, Attal M, Belch A, Knop S, Joshua D, Sezer O, Ludwig H, Vesole D, Blade J, Kyle R, Westin J, Weber D, Bringhen S, Niesvizky R, Waage A, von Lilienfeld-Toal M, Lonial S, Morgan GJ, Orlowski RZ, Shimizu K, Anderson KC, Boccadoro M, Durie BG, Sonneveld P, Hussein MA, International Myeloma Working G (2008) Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 22(2):414–423. https://doi.org/10.1038/sj.leu.2405062 CrossRefGoogle Scholar
- 6.Hinduja A, Limaye K, Ravilla R, Sasapu A, Papanikolaou X, Wei L, Torbey M, Waheed S (2016) Spectrum of cerebrovascular disease in patients with multiple myeloma undergoing chemotherapy-results of a case control study. PLoS ONE 11(11):e0166627. https://doi.org/10.1371/journal.pone.0166627 CrossRefGoogle Scholar
- 7.Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A (2013) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31(17):2189–2204. https://doi.org/10.1200/JCO.2013.49.1118 CrossRefGoogle Scholar
- 8.Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 33(6):654–656. https://doi.org/10.1200/JCO.2014.59.7351 CrossRefGoogle Scholar
- 12.Terpos E, Kleber M, Engelhardt M, Zweegman S, Gay F, Kastritis E, van de Donk NW, Bruno B, Sezer O, Broijl A, Bringhen S, Beksac M, Larocca A, Hajek R, Musto P, Johnsen HE, Morabito F, Ludwig H, Cavo M, Einsele H, Sonneveld P, Dimopoulos MA, Palumbo A, European Myeloma N (2015) European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica 100(10):1254–1266. https://doi.org/10.3324/haematol.2014.117176 CrossRefGoogle Scholar
- 13.Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Hehlmann R, Hoffman R, Kiladjian JJ, Kroger N, Mesa R, McMullin MF, Pardanani A, Passamonti F, Vannucchi AM, Reiter A, Silver RT, Verstovsek S, Tefferi A, European L (2011) Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 29(6):761–770. https://doi.org/10.1200/JCO.2010.31.8436 CrossRefGoogle Scholar
- 14.Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A (2012) Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 120(26):5128–5133. https://doi.org/10.1182/blood-2012-07-444067 CrossRefGoogle Scholar
- 15.Barbui T, Vannucchi AM, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Finazzi G, Carobbio A, Thiele J, Passamonti F, Falcone C, Tefferi A (2015) Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J 5:e369. https://doi.org/10.1038/bcj.2015.94 CrossRefGoogle Scholar
- 16.Kreher S, Ochsenreither S, Trappe RU, Pabinger I, Bergmann F, Petrides PE, Koschmieder S, Matzdorff A, Tiede A, Griesshammer M, Riess H, Haemostasis Working Party of the German Society of H, Oncology, Austrian Society of H, Oncology, Society of T, Haemostasis R (2014) Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (OGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.). Ann Hematol 93(12):1953–1963. https://doi.org/10.1007/s00277-014-2224-8 CrossRefGoogle Scholar
- 18.Koh Y, Bang SM, Lee JH, Yoon HJ, Do YR, Ryoo HM, Lee N, Kim SJ, Kim K, Yoon SS, Won JH, Mun YC, Lee MH, Rhee KH, Kim HJ, Eom H, Kim MK, Shin HC, Korean Multiple Myeloma Working P (2010) Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide. Ann Hematol 89(2):201–206. https://doi.org/10.1007/s00277-009-0807-6 CrossRefGoogle Scholar
- 20.Kato A, Takano H, Ichikawa A, Koshino M, Igarashi A, Hattori K, Nagata K (2013) A retrospective cohort study of venous thromboembolism(VTE) in 1035 Japanese myeloma patients treated with thalidomide; lower incidence without statistically significant association between specific risk factors and development of VTE and effects of thromboprophylaxis with aspirin and warfarin. Thrombos Res 131(2):140–144. https://doi.org/10.1016/j.thromres.2012.11.014 CrossRefGoogle Scholar
- 21.Ichinohe T, Kuroda Y, Okamoto S, Matsue K, Iida S, Sunami K, Komeno T, Suzuki K, Ando K, Taniwaki M, Tobinai K, Chou T, Kaneko H, Iwasaki H, Uemura C, Tamakoshi H, Zaki MH, Doerr T, Hagiwara S (2016) A multicenter phase 2 study of pomalidomide plus dexamethasone in patients with relapsed and refractory multiple myeloma: the Japanese MM-011 trial. Exp Hematol Oncol 5:11. https://doi.org/10.1186/s40164-016-0040-7 CrossRefGoogle Scholar
- 22.Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M (2013) Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 14(11):1055–1066. https://doi.org/10.1016/s1470-2045(13)70380-2 CrossRefGoogle Scholar
- 23.Richard H. White CRK (2009) Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res 123, Supple. 4:S11–S17Google Scholar
- 25.Palmaro A, Rouge-Bugat ME, Gauthier M, Despas F, Moulis G, Lapeyre-Mestre M (2017) Real-life practices for preventing venous thromboembolism in multiple myeloma patients: a cohort study from the French health insurance database. Pharmacoepidemiol Drug Saf 26(5):578–586. https://doi.org/10.1002/pds.4180 CrossRefGoogle Scholar
- 28.Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A (2012) Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 119(4):933–939. https://doi.org/10.1182/blood-2011-03-344333 CrossRefGoogle Scholar