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.
N1 - Funding Information:
This work was supported by the Charif Souki Cancer Research Grant and in part by the University of Texas MD Anderson Cancer Center Leukemia Specialized Programs of Research Excellence (SPORE) grant P50 CA100632.
Funding Information:
Jorge E. Cortes reports grants and personal fees from Astellas Pharma US, Daiichi Sankyo, Novartis, Jazz Pharmaceuticals, Pfizer, and ImmunoGen and grants from Celgene, outside the submitted work. Marina Konopleva reports grants from AbbVie, Genetech, and Cellectis; funding for trial support from Stemline Therapeutics and Eli Lilly and Company; personal fees from Roche, all outside the submitted work; and owns stock options in Reata Pharmaceuticals. The remaining authors made no disclosures.
Publisher Copyright:
© 2018 American Cancer Society
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.
KW - acute myeloid leukemia
KW - historic
KW - results
KW - second salvage
KW - survival
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U2 - 10.1002/cncr.31370
DO - 10.1002/cncr.31370
M3 - Article
C2 - 29645075
AN - SCOPUS:85045276776
SN - 0008-543X
VL - 124
SP - 2534
EP - 2540
JO - Cancer
JF - Cancer
IS - 12
ER -