A systematic review and meta-analysis of the efficacy and adverse events of azacitidine-plus-lenalidomide treatment for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemiaFootnote¹

1 Supplemental data for this article can be accessed https://doi.org/10.1080/16078454.2019.1631425.

References

• Society AC. Cancer Facts & Figures. 2014. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. Accessed 1 October 2018.
   Google Scholar
• Kantarjian H, O’Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090–1098. doi: 10.1002/cncr.21723
   PubMed Web of Science ®Google Scholar
• Juliusson G. Older patients with acute myeloid leukemia benefit from intensive chemotherapy: an update from the Swedish acute leukemia Registry. Clin Lymphoma Myeloma Leuk. 2011;11(Suppl 1):S54–S59. doi: 10.1016/j.clml.2011.02.003
   PubMedGoogle Scholar
• Owattanapanich W, Utchariyaprasit E, Tantiworawit A, et al. Improved survival of elderly-fit patients with acute myeloid leukemia requiring intensive therapy: 3-year multicenter analysis from TALWG. Clin Lymphoma Myeloma Leuk. 2018;18:e509–e514. doi: 10.1016/j.clml.2018.08.002
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network (NCCN). Acute myeloid leukemia (version 2.2018). Available from: https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed 20 October 2018.
   Google Scholar
• National Comprehensive Cancer Network (NCCN). Myelodysplastic syndromes (version 2.2019). Available from: https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf. Accessed 20 October 2018.
   Google Scholar
• Kubasch AS, Platzbecker U. Beyond the edge of hypomethylating agents: novel combination strategies for older adults with advanced MDS and AML. Cancers (Basel). 2018;10. DOI: 10.3390/cancers10060158
   PubMed Web of Science ®Google Scholar
• Ades L, Guerci-Bresler A, Cony-Makhoul P, et al. A phase II study of the efficacy and safety of an intensified schedule of azacitidine in intermediate-2 and high risk patients with myelodysplastic syndromes: a study by the Groupe Francophone des myelodysplasies (GFM). Haematologica. 2018. DOI:10.3324/haematol.2018.203885
   Web of Science ®Google Scholar
• List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355:1456–1465. doi: 10.1056/NEJMoa061292
   PubMed Web of Science ®Google Scholar
• Scherman E, Malak S, Perot C, et al. Interest of the association azacitidine–lenalidomide as frontline therapy in high-risk myelodysplasia or acute myeloid leukemia with complex karyotype. Leukemia. 2012;26:822–824. doi: 10.1038/leu.2011.284
   PubMed Web of Science ®Google Scholar
• Sekeres MA, Tiu RV, Komrokji R, et al. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood. 2012;120:4945–4951. doi: 10.1182/blood-2012-06-434639
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Braulke F, Kundgen A, et al. Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study. Leukemia. 2013;27:1403–1407. doi: 10.1038/leu.2013.26
   PubMed Web of Science ®Google Scholar
• Pollyea DA, Zehnder J, Coutre S, et al. Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica. 2013;98:591–596. doi: 10.3324/haematol.2012.076414
   PubMed Web of Science ®Google Scholar
• Ramsingh G, Westervelt P, Cashen AF, et al. A phase 1 study of concomitant high-dose lenalidomide and 5-azacitidine induction in the treatment of AML. Leukemia. 2013;27:725–728. doi: 10.1038/leu.2012.214
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Daver N, Jabbour E, et al. Sequential azacitidine and lenalidomide in patients with high-risk myelodysplastic syndromes and acute myeloid leukaemia: a single-arm, phase 1/2 study. Lancet Haematol. 2015;2:e12–e20. doi: 10.1016/S2352-3026(14)00026-X
   PubMed Web of Science ®Google Scholar
• Mittelman M, Filanovsky K, Ofran Y, et al. Azacitidine–lenalidomide (ViLen) combination yields a high response rate in higher risk myelodysplastic syndromes (MDS)-ViLen-01 protocol. Ann Hematol. 2016;95:1811–1818. doi: 10.1007/s00277-016-2776-x
   PubMed Web of Science ®Google Scholar
• Narayan R, Garcia JS, Percival ME, et al. Sequential azacitidine plus lenalidomide in previously treated elderly patients with acute myeloid leukemia and higher risk myelodysplastic syndrome. Leuk Lymphoma. 2016;57:609–615. doi: 10.3109/10428194.2015.1091930
   PubMed Web of Science ®Google Scholar
• Sekeres MA, Othus M, List AF, et al. Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup study SWOG S1117. J Clin Oncol. 2017;35:2745–2753. doi: 10.1200/JCO.2015.66.2510
   PubMed Web of Science ®Google Scholar
• Medeiros BC, McCaul K, Kambhampati S, et al. Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide, or azacitidine in persons 65 years and over with newly-diagnosed acute myeloid leukemia. Haematologica. 2018;103:101–106. doi: 10.3324/haematol.2017.172353
   PubMed Web of Science ®Google Scholar
• Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Br Med J. 2009;339:b2535. doi: 10.1136/bmj.b2535
   PubMed Web of Science ®Google Scholar
• Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the international working group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–425. doi: 10.1182/blood-2005-10-4149
   PubMed Web of Science ®Google Scholar
• Common Terminology Criteria for Adverse Events version 3.0. Available from: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed 20 October 2018.
   Google Scholar
• Mathes T, Kuss O. A comparison of methods for meta-analysis of a small number of studies with binary outcomes. Res Synth Methods. 2018;9:366–381.
   PubMed Web of Science ®Google Scholar
• Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. Br Med J. 2003;327:557–660. doi: 10.1136/bmj.327.7414.557
   PubMed Web of Science ®Google Scholar
• Shapiro RM, Lazo-Langner A. Systematic review of azacitidine regimens in myelodysplastic syndrome and acute myeloid leukemia. BMC Hematol. 2018;18(3).
   PubMedGoogle Scholar
• Pleyer L, Burgstaller S, Stauder R, et al. Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications. J Hematol Oncol. 2016;9:39. doi: 10.1186/s13045-016-0263-4
   PubMed Web of Science ®Google Scholar
• Gao C, Wang J, Li Y, et al. Incidence and risk of hematologic toxicities with hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukopenia: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97:e11860. doi: 10.1097/MD.0000000000011860
   PubMed Web of Science ®Google Scholar