Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort

Maximilian Stahl; Michelle DeVeaux; Pau Montesinos; Raphael Itzykson; Ellen K. Ritchie; Mikkael A. Sekeres; John D. Barnard; Nikolai A. Podoltsev; Andrew M. Brunner; Rami S. Komrokji; Vijaya R. Bhatt; Aref Al-Kali; Thomas Cluzeau; Valeria Santini; Amir T. Fathi; Gail J. Roboz; Pierre Fenaux; Mark R. Litzow; Sarah Perreault; Tae Kon Kim; Thomas Prebet; Norbert Vey; Vivek Verma; Ulrich Germing; Juan Miguel Bergua; Josefina Serrano; Steven D. Gore; Amer M. Zeidan

doi:10.1182/bloodadvances.2018016121

Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort

Maximilian Stahl, Michelle DeVeaux, Pau Montesinos, Raphael Itzykson, Ellen K. Ritchie, Mikkael A. Sekeres, John D. Barnard, Nikolai A. Podoltsev, Andrew M. Brunner, Rami S. Komrokji, Vijaya R. Bhatt, Aref Al-Kali, Thomas Cluzeau, Valeria Santini, Amir T. Fathi, Gail J. Roboz, Pierre Fenaux, Mark R. Litzow, Sarah Perreault, Tae Kon KimThomas Prebet, Norbert Vey, Vivek Verma, Ulrich Germing, Juan Miguel Bergua, Josefina Serrano, Steven D. Gore, Amer M. Zeidan

Hematology

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Abstract

Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

Original language	English (US)
Pages (from-to)	923-932
Number of pages	10
Journal	Blood Advances
Volume	2
Issue number	8
DOIs	https://doi.org/10.1182/bloodadvances.2018016121
State	Published - Apr 24 2018

ASJC Scopus subject areas

Hematology

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10.1182/bloodadvances.2018016121

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Stahl, M., DeVeaux, M., Montesinos, P., Itzykson, R., Ritchie, E. K., Sekeres, M. A., Barnard, J. D., Podoltsev, N. A., Brunner, A. M., Komrokji, R. S., Bhatt, V. R., Al-Kali, A., Cluzeau, T., Santini, V., Fathi, A. T., Roboz, G. J., Fenaux, P., Litzow, M. R., Perreault, S., ... Zeidan, A. M. (2018). Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort. Blood Advances, 2(8), 923-932. https://doi.org/10.1182/bloodadvances.2018016121

Stahl, M, DeVeaux, M, Montesinos, P, Itzykson, R, Ritchie, EK, Sekeres, MA, Barnard, JD, Podoltsev, NA, Brunner, AM, Komrokji, RS, Bhatt, VR, Al-Kali, A, Cluzeau, T, Santini, V, Fathi, AT, Roboz, GJ, Fenaux, P, Litzow, MR, Perreault, S, Kim, TK, Prebet, T, Vey, N, Verma, V, Germing, U, Bergua, JM, Serrano, J, Gore, SD & Zeidan, AM 2018, 'Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort', Blood Advances, vol. 2, no. 8, pp. 923-932. https://doi.org/10.1182/bloodadvances.2018016121

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title = "Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort",

abstract = "Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.",

author = "Maximilian Stahl and Michelle DeVeaux and Pau Montesinos and Raphael Itzykson and Ritchie, {Ellen K.} and Sekeres, {Mikkael A.} and Barnard, {John D.} and Podoltsev, {Nikolai A.} and Brunner, {Andrew M.} and Komrokji, {Rami S.} and Bhatt, {Vijaya R.} and Aref Al-Kali and Thomas Cluzeau and Valeria Santini and Fathi, {Amir T.} and Roboz, {Gail J.} and Pierre Fenaux and Litzow, {Mark R.} and Sarah Perreault and Kim, {Tae Kon} and Thomas Prebet and Norbert Vey and Vivek Verma and Ulrich Germing and Bergua, {Juan Miguel} and Josefina Serrano and Gore, {Steven D.} and Zeidan, {Amer M.}",

note = "Publisher Copyright: {\textcopyright} 2018 by The American Society of Hematology.",

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doi = "10.1182/bloodadvances.2018016121",

language = "English (US)",

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T1 - Hypomethylating agents in relapsed and refractory AML

T2 - Outcomes and their predictors in a large international patient cohort

AU - Stahl, Maximilian

AU - DeVeaux, Michelle

AU - Montesinos, Pau

AU - Itzykson, Raphael

AU - Ritchie, Ellen K.

AU - Sekeres, Mikkael A.

AU - Barnard, John D.

AU - Podoltsev, Nikolai A.

AU - Brunner, Andrew M.

AU - Komrokji, Rami S.

AU - Bhatt, Vijaya R.

AU - Al-Kali, Aref

AU - Cluzeau, Thomas

AU - Santini, Valeria

AU - Fathi, Amir T.

AU - Roboz, Gail J.

AU - Fenaux, Pierre

AU - Litzow, Mark R.

AU - Perreault, Sarah

AU - Kim, Tae Kon

AU - Prebet, Thomas

AU - Vey, Norbert

AU - Verma, Vivek

AU - Germing, Ulrich

AU - Bergua, Juan Miguel

AU - Serrano, Josefina

AU - Gore, Steven D.

AU - Zeidan, Amer M.

PY - 2018/4/24

Y1 - 2018/4/24

N2 - Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

AB - Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

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Hypomethylating agents in relapsed and refractory AML: Outcomes and their predictors in a large international patient cohort

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