Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach

Prajwal Chaitanya Boddu, Hagop M. Kantarjian, Farhad Ravandi, Guillermo Garcia-Manero, Srdan Verstovsek, Elias J. Jabbour, Koichi Takahashi, Kapil Bhalla, Marina Konopleva, Courtney D. DiNardo, Maro Ohanian, Naveen Pemmaraju, Nitin Jain, Sherry Pierce, William G. Wierda, Jorge E. Cortes, Tapan M. Kadia

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important. METHODS: s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine–based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria. RESULTS: Complete remission rates were statistically lower in the HMA group (36%) versus the IC (46%), CPX-351 (45%), and LDAC groups (43%). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P =.048). Only 4.3% of the IC patients proceeded to transplantation, whereas 10.3% of the patients on lower intensity regimens did (P =.001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P =.75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis. CONCLUSIONS: Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies. Cancer 2017;123:3050–60.

Original languageEnglish (US)
Pages (from-to)3050-3060
Number of pages11
JournalCancer
Volume123
Issue number16
DOIs
StatePublished - Aug 15 2017
Externally publishedYes

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Acute Myeloid Leukemia
Therapeutics
Survival
Drug Therapy
Karyotype
Myelodysplastic Syndromes
Cytarabine
Multivariate Analysis
Transplantation

Keywords

  • acute myelogenous leukemia
  • CPX-351
  • epigenetic
  • hypomethylating
  • intensive
  • low-dose cytarabine
  • outcomes
  • secondary

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Boddu, P. C., Kantarjian, H. M., Ravandi, F., Garcia-Manero, G., Verstovsek, S., Jabbour, E. J., ... Kadia, T. M. (2017). Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. Cancer, 123(16), 3050-3060. https://doi.org/10.1002/cncr.30704

Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. / Boddu, Prajwal Chaitanya; Kantarjian, Hagop M.; Ravandi, Farhad; Garcia-Manero, Guillermo; Verstovsek, Srdan; Jabbour, Elias J.; Takahashi, Koichi; Bhalla, Kapil; Konopleva, Marina; DiNardo, Courtney D.; Ohanian, Maro; Pemmaraju, Naveen; Jain, Nitin; Pierce, Sherry; Wierda, William G.; Cortes, Jorge E.; Kadia, Tapan M.

In: Cancer, Vol. 123, No. 16, 15.08.2017, p. 3050-3060.

Research output: Contribution to journalArticle

Boddu, PC, Kantarjian, HM, Ravandi, F, Garcia-Manero, G, Verstovsek, S, Jabbour, EJ, Takahashi, K, Bhalla, K, Konopleva, M, DiNardo, CD, Ohanian, M, Pemmaraju, N, Jain, N, Pierce, S, Wierda, WG, Cortes, JE & Kadia, TM 2017, 'Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach', Cancer, vol. 123, no. 16, pp. 3050-3060. https://doi.org/10.1002/cncr.30704
Boddu PC, Kantarjian HM, Ravandi F, Garcia-Manero G, Verstovsek S, Jabbour EJ et al. Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. Cancer. 2017 Aug 15;123(16):3050-3060. https://doi.org/10.1002/cncr.30704
Boddu, Prajwal Chaitanya ; Kantarjian, Hagop M. ; Ravandi, Farhad ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Jabbour, Elias J. ; Takahashi, Koichi ; Bhalla, Kapil ; Konopleva, Marina ; DiNardo, Courtney D. ; Ohanian, Maro ; Pemmaraju, Naveen ; Jain, Nitin ; Pierce, Sherry ; Wierda, William G. ; Cortes, Jorge E. ; Kadia, Tapan M. / Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. In: Cancer. 2017 ; Vol. 123, No. 16. pp. 3050-3060.
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abstract = "BACKGROUND: The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important. METHODS: s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine–based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria. RESULTS: Complete remission rates were statistically lower in the HMA group (36{\%}) versus the IC (46{\%}), CPX-351 (45{\%}), and LDAC groups (43{\%}). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P =.048). Only 4.3{\%} of the IC patients proceeded to transplantation, whereas 10.3{\%} of the patients on lower intensity regimens did (P =.001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P =.75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis. CONCLUSIONS: Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies. Cancer 2017;123:3050–60.",
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T1 - Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach

AU - Boddu, Prajwal Chaitanya

AU - Kantarjian, Hagop M.

AU - Ravandi, Farhad

AU - Garcia-Manero, Guillermo

AU - Verstovsek, Srdan

AU - Jabbour, Elias J.

AU - Takahashi, Koichi

AU - Bhalla, Kapil

AU - Konopleva, Marina

AU - DiNardo, Courtney D.

AU - Ohanian, Maro

AU - Pemmaraju, Naveen

AU - Jain, Nitin

AU - Pierce, Sherry

AU - Wierda, William G.

AU - Cortes, Jorge E.

AU - Kadia, Tapan M.

PY - 2017/8/15

Y1 - 2017/8/15

N2 - BACKGROUND: The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important. METHODS: s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine–based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria. RESULTS: Complete remission rates were statistically lower in the HMA group (36%) versus the IC (46%), CPX-351 (45%), and LDAC groups (43%). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P =.048). Only 4.3% of the IC patients proceeded to transplantation, whereas 10.3% of the patients on lower intensity regimens did (P =.001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P =.75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis. CONCLUSIONS: Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies. Cancer 2017;123:3050–60.

AB - BACKGROUND: The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important. METHODS: s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine–based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria. RESULTS: Complete remission rates were statistically lower in the HMA group (36%) versus the IC (46%), CPX-351 (45%), and LDAC groups (43%). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P =.048). Only 4.3% of the IC patients proceeded to transplantation, whereas 10.3% of the patients on lower intensity regimens did (P =.001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P =.75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis. CONCLUSIONS: Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies. Cancer 2017;123:3050–60.

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KW - CPX-351

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KW - intensive

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