Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome

Naval Daver, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Gautam Borthakur, Mark Brandt, Sherry Pierce, Kenneth Vaughan, Jing Ning, Graciela M. Nogueras González, Keyur Patel, Jeffery Jorgensen, Naveen Pemmaraju, Tapan Kadia, Marina Konopleva, Michael Andreeff, Courtney DiNardo, Jorge Cortes, Renee Ward, Adam CraigFarhad Ravandi

Research output: Contribution to journalArticle

Abstract

Vosaroxin is an anti-cancer quinolone-derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥60 years of age with newly diagnosed acute myeloid leukemia (n=58) or myelodysplastic syndrome (≥10% blasts) (n=7) in a phase II non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on days 1 and 4 with decitabine 20 mg/m2 on days 1-5 every 4-6 weeks for up to seven cycles. Due to a high incidence of mucositis the subsequent 43 patients were given vosaroxin 70 mg/m2 on days 1 and 4. These 65 patients, with a median age of 69 years (range, 60-78), some of whom with secondary leukemia (22%), adverse karyotype (35%), or TP53 mutation (20%), are evaluable. The overall response rate was 74% including complete remission in 31 (48%), complete remission with incomplete platelet recovery in 11 (17%), and complete remission with incomplete count recovery in six (9%). The median number of cycles to response was one (range, 1-4). Grade 3/4 mucositis was noted in 17% of all patients. The 70 mg/m2 induction dose of vosaroxin was associated with similar rates of overall response (74% versus 73%) and complete remission (51% versus 41%, P=0.44), reduced incidence of mucositis (30% versus 59%, P=0.02), reduced 8-week mortality (9% versus 23%; P=0.14), and improved median overall survival (14.6 months versus 5.5 months, P=0.007). Minimal residual disease-negative status by multiparametric flow-cytometry at response (± 3 months) was achieved in 21 of 39 (54%) evaluable responders and was associated with better median overall survival (34.0 months versus 8.3 months, P=0.023). In conclusion, the combination of vosaroxin with decitabine is effective and well tolerated at a dose of 70 mg/m2 and warrants randomized prospective evaluation.

Original languageEnglish (US)
Pages (from-to)1709-1717
Number of pages9
JournalHaematologica
Volume102
Issue number10
DOIs
StatePublished - Sep 30 2017
Externally publishedYes

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decitabine
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Mucositis
Topoisomerase II Inhibitors
Survival
Quinolones
Incidence
Residual Neoplasm
Karyotype
vosaroxin
Flow Cytometry
Leukemia
Blood Platelets

ASJC Scopus subject areas

  • Hematology

Cite this

Daver, N., Kantarjian, H., Garcia-Manero, G., Jabbour, E., Borthakur, G., Brandt, M., ... Ravandi, F. (2017). Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Haematologica, 102(10), 1709-1717. https://doi.org/10.3324/haematol.2017.168732

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. / Daver, Naval; Kantarjian, Hagop; Garcia-Manero, Guillermo; Jabbour, Elias; Borthakur, Gautam; Brandt, Mark; Pierce, Sherry; Vaughan, Kenneth; Ning, Jing; Nogueras González, Graciela M.; Patel, Keyur; Jorgensen, Jeffery; Pemmaraju, Naveen; Kadia, Tapan; Konopleva, Marina; Andreeff, Michael; DiNardo, Courtney; Cortes, Jorge; Ward, Renee; Craig, Adam; Ravandi, Farhad.

In: Haematologica, Vol. 102, No. 10, 30.09.2017, p. 1709-1717.

Research output: Contribution to journalArticle

Daver, N, Kantarjian, H, Garcia-Manero, G, Jabbour, E, Borthakur, G, Brandt, M, Pierce, S, Vaughan, K, Ning, J, Nogueras González, GM, Patel, K, Jorgensen, J, Pemmaraju, N, Kadia, T, Konopleva, M, Andreeff, M, DiNardo, C, Cortes, J, Ward, R, Craig, A & Ravandi, F 2017, 'Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome', Haematologica, vol. 102, no. 10, pp. 1709-1717. https://doi.org/10.3324/haematol.2017.168732
Daver, Naval ; Kantarjian, Hagop ; Garcia-Manero, Guillermo ; Jabbour, Elias ; Borthakur, Gautam ; Brandt, Mark ; Pierce, Sherry ; Vaughan, Kenneth ; Ning, Jing ; Nogueras González, Graciela M. ; Patel, Keyur ; Jorgensen, Jeffery ; Pemmaraju, Naveen ; Kadia, Tapan ; Konopleva, Marina ; Andreeff, Michael ; DiNardo, Courtney ; Cortes, Jorge ; Ward, Renee ; Craig, Adam ; Ravandi, Farhad. / Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. In: Haematologica. 2017 ; Vol. 102, No. 10. pp. 1709-1717.
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T1 - Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome

AU - Daver, Naval

AU - Kantarjian, Hagop

AU - Garcia-Manero, Guillermo

AU - Jabbour, Elias

AU - Borthakur, Gautam

AU - Brandt, Mark

AU - Pierce, Sherry

AU - Vaughan, Kenneth

AU - Ning, Jing

AU - Nogueras González, Graciela M.

AU - Patel, Keyur

AU - Jorgensen, Jeffery

AU - Pemmaraju, Naveen

AU - Kadia, Tapan

AU - Konopleva, Marina

AU - Andreeff, Michael

AU - DiNardo, Courtney

AU - Cortes, Jorge

AU - Ward, Renee

AU - Craig, Adam

AU - Ravandi, Farhad

PY - 2017/9/30

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N2 - Vosaroxin is an anti-cancer quinolone-derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥60 years of age with newly diagnosed acute myeloid leukemia (n=58) or myelodysplastic syndrome (≥10% blasts) (n=7) in a phase II non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on days 1 and 4 with decitabine 20 mg/m2 on days 1-5 every 4-6 weeks for up to seven cycles. Due to a high incidence of mucositis the subsequent 43 patients were given vosaroxin 70 mg/m2 on days 1 and 4. These 65 patients, with a median age of 69 years (range, 60-78), some of whom with secondary leukemia (22%), adverse karyotype (35%), or TP53 mutation (20%), are evaluable. The overall response rate was 74% including complete remission in 31 (48%), complete remission with incomplete platelet recovery in 11 (17%), and complete remission with incomplete count recovery in six (9%). The median number of cycles to response was one (range, 1-4). Grade 3/4 mucositis was noted in 17% of all patients. The 70 mg/m2 induction dose of vosaroxin was associated with similar rates of overall response (74% versus 73%) and complete remission (51% versus 41%, P=0.44), reduced incidence of mucositis (30% versus 59%, P=0.02), reduced 8-week mortality (9% versus 23%; P=0.14), and improved median overall survival (14.6 months versus 5.5 months, P=0.007). Minimal residual disease-negative status by multiparametric flow-cytometry at response (± 3 months) was achieved in 21 of 39 (54%) evaluable responders and was associated with better median overall survival (34.0 months versus 8.3 months, P=0.023). In conclusion, the combination of vosaroxin with decitabine is effective and well tolerated at a dose of 70 mg/m2 and warrants randomized prospective evaluation.

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