Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000

Hagop M. Kantarjian, Courtney D. DiNardo, Graciela M. Nogueras-Gonzalez, Tapan M. Kadia, Elias Jabbour, Carlos E. Bueso-Ramos, Susan M. O'Brien, Marina Konopleva, Nitin B. Jain, Naval G. Daver, Elizabeth J. Shpall, Richard E. Champlin, Aron Simkins, Guillermo Garcia-Manero, Michael J. Keating, Xuelin Huang, Jorge E. Cortes, Sherry A. Pierce, Farhad Ravandi, Emil J. Freireich

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival. METHODS: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of the 673 patients (13%) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets < 50 × 109/L (P <.001), complex karyotype with ≥3 chromosomal abnormalities (P =.02), regimens that did not include cytarabine or hypomethylating agents (P =.014), and no prior CR lasting ≥12 months with frontline or salvage 1 therapies (P <.001). The independent adverse factors associated with worse survival were age ≥60 years (P =.01), platelets < 50 × 109/L (P =.02), peripheral blasts ≥ 20% (P =.03), albumin ≤ 3 g/dL (P =.04), and complex karyotype (P =.003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. Cancer 2018;124:2534-40.

Original languageEnglish (US)
Pages (from-to)2534-2540
Number of pages7
JournalCancer
Volume124
Issue number12
DOIs
StatePublished - Jun 15 2018
Externally publishedYes

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Salvage Therapy
Acute Myeloid Leukemia
Survival
Cytarabine
Karyotype
Blood Platelets
Confidence Intervals
Platelet Count
Chromosome Aberrations
Albumins
Therapeutics
Multivariate Analysis
Survival Rate

Keywords

  • acute myeloid leukemia
  • historic
  • results
  • second salvage
  • survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kantarjian, H. M., DiNardo, C. D., Nogueras-Gonzalez, G. M., Kadia, T. M., Jabbour, E., Bueso-Ramos, C. E., ... Freireich, E. J. (2018). Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000. Cancer, 124(12), 2534-2540. https://doi.org/10.1002/cncr.31370

Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000. / Kantarjian, Hagop M.; DiNardo, Courtney D.; Nogueras-Gonzalez, Graciela M.; Kadia, Tapan M.; Jabbour, Elias; Bueso-Ramos, Carlos E.; O'Brien, Susan M.; Konopleva, Marina; Jain, Nitin B.; Daver, Naval G.; Shpall, Elizabeth J.; Champlin, Richard E.; Simkins, Aron; Garcia-Manero, Guillermo; Keating, Michael J.; Huang, Xuelin; Cortes, Jorge E.; Pierce, Sherry A.; Ravandi, Farhad; Freireich, Emil J.

In: Cancer, Vol. 124, No. 12, 15.06.2018, p. 2534-2540.

Research output: Contribution to journalArticle

Kantarjian, HM, DiNardo, CD, Nogueras-Gonzalez, GM, Kadia, TM, Jabbour, E, Bueso-Ramos, CE, O'Brien, SM, Konopleva, M, Jain, NB, Daver, NG, Shpall, EJ, Champlin, RE, Simkins, A, Garcia-Manero, G, Keating, MJ, Huang, X, Cortes, JE, Pierce, SA, Ravandi, F & Freireich, EJ 2018, 'Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000', Cancer, vol. 124, no. 12, pp. 2534-2540. https://doi.org/10.1002/cncr.31370
Kantarjian HM, DiNardo CD, Nogueras-Gonzalez GM, Kadia TM, Jabbour E, Bueso-Ramos CE et al. Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000. Cancer. 2018 Jun 15;124(12):2534-2540. https://doi.org/10.1002/cncr.31370
Kantarjian, Hagop M. ; DiNardo, Courtney D. ; Nogueras-Gonzalez, Graciela M. ; Kadia, Tapan M. ; Jabbour, Elias ; Bueso-Ramos, Carlos E. ; O'Brien, Susan M. ; Konopleva, Marina ; Jain, Nitin B. ; Daver, Naval G. ; Shpall, Elizabeth J. ; Champlin, Richard E. ; Simkins, Aron ; Garcia-Manero, Guillermo ; Keating, Michael J. ; Huang, Xuelin ; Cortes, Jorge E. ; Pierce, Sherry A. ; Ravandi, Farhad ; Freireich, Emil J. / Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000. In: Cancer. 2018 ; Vol. 124, No. 12. pp. 2534-2540.
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abstract = "BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival. METHODS: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of the 673 patients (13{\%}) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95{\%} confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16{\%} (95{\%} confidence interval, 14{\%}-19{\%}). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets < 50 × 109/L (P <.001), complex karyotype with ≥3 chromosomal abnormalities (P =.02), regimens that did not include cytarabine or hypomethylating agents (P =.014), and no prior CR lasting ≥12 months with frontline or salvage 1 therapies (P <.001). The independent adverse factors associated with worse survival were age ≥60 years (P =.01), platelets < 50 × 109/L (P =.02), peripheral blasts ≥ 20{\%} (P =.03), albumin ≤ 3 g/dL (P =.04), and complex karyotype (P =.003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. Cancer 2018;124:2534-40.",
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TY - JOUR

T1 - Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000

AU - Kantarjian, Hagop M.

AU - DiNardo, Courtney D.

AU - Nogueras-Gonzalez, Graciela M.

AU - Kadia, Tapan M.

AU - Jabbour, Elias

AU - Bueso-Ramos, Carlos E.

AU - O'Brien, Susan M.

AU - Konopleva, Marina

AU - Jain, Nitin B.

AU - Daver, Naval G.

AU - Shpall, Elizabeth J.

AU - Champlin, Richard E.

AU - Simkins, Aron

AU - Garcia-Manero, Guillermo

AU - Keating, Michael J.

AU - Huang, Xuelin

AU - Cortes, Jorge E.

AU - Pierce, Sherry A.

AU - Ravandi, Farhad

AU - Freireich, Emil J.

PY - 2018/6/15

Y1 - 2018/6/15

N2 - BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival. METHODS: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of the 673 patients (13%) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets < 50 × 109/L (P <.001), complex karyotype with ≥3 chromosomal abnormalities (P =.02), regimens that did not include cytarabine or hypomethylating agents (P =.014), and no prior CR lasting ≥12 months with frontline or salvage 1 therapies (P <.001). The independent adverse factors associated with worse survival were age ≥60 years (P =.01), platelets < 50 × 109/L (P =.02), peripheral blasts ≥ 20% (P =.03), albumin ≤ 3 g/dL (P =.04), and complex karyotype (P =.003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. Cancer 2018;124:2534-40.

AB - BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival. METHODS: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of the 673 patients (13%) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets < 50 × 109/L (P <.001), complex karyotype with ≥3 chromosomal abnormalities (P =.02), regimens that did not include cytarabine or hypomethylating agents (P =.014), and no prior CR lasting ≥12 months with frontline or salvage 1 therapies (P <.001). The independent adverse factors associated with worse survival were age ≥60 years (P =.01), platelets < 50 × 109/L (P =.02), peripheral blasts ≥ 20% (P =.03), albumin ≤ 3 g/dL (P =.04), and complex karyotype (P =.003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. Cancer 2018;124:2534-40.

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KW - historic

KW - results

KW - second salvage

KW - survival

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