Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia

Brian Ball, Rami S. Komrokji, Lionel Adès, Mikkael A. Sekeres, Amy Dezern, Lisa Pleyer, Norbert Vey, Antonio Almeida, Ulrich Germing, Thomas Cluzeau, Uwe Platzbecker, Steven D. Gore, Pierre Fenaux, Thomas Prebet

Research output: Contribution to journalArticle

Abstract

Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients afterHMAfailure. Patients received 713, intermediate-to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens. For the MDS cohort (n 5 307), the overall response rate (ORR) was 41%; median overall survival (OS) was 10.8 months, and 40% of responding patients bridged to allogeneic stem cell transplant (allo-SCT). For the AML cohort (n 5 59), the ORR was 32%, OS 6 months, and 42% of responding patients bridged to allo-SCT. Prognostic factors for response in MDS included adverse cytogenetics (odds ratio [OR], 0.46, P 5 .01), age $65 years (OR, 0.47; P, .01), and use of IDAC (OR, 2.91, P 5 .01). Shorter survival was associated with adverse cytogenetics (hazard ratio [HR], 1.43; P 5 .06). In the AML cohort, OS was decreased by disease progression at time of HMA failure (HR, 2.66; P 5 .02) and prolonged with use of an anthracycline-containing regimen (HR, 0.37; P 5 .01). In conclusion, intensive chemotherapy after HMA failure may be a reasonable treatment option for selected patients as a bridge to allogeneic transplantation and should be considered a potential platform for future investigations.

Original languageEnglish (US)
Pages (from-to)2063-2071
Number of pages9
JournalBlood Advances
Volume2
Issue number16
DOIs
StatePublished - Aug 28 2018

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Induction Chemotherapy
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Survival
Odds Ratio
Homologous Transplantation
Cytogenetics
Stem Cells
Purine Nucleosides
Transplants
Remission Induction
Anthracyclines
Cytarabine
Disease Progression
Survival Rate
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia. / Ball, Brian; Komrokji, Rami S.; Adès, Lionel; Sekeres, Mikkael A.; Dezern, Amy; Pleyer, Lisa; Vey, Norbert; Almeida, Antonio; Germing, Ulrich; Cluzeau, Thomas; Platzbecker, Uwe; Gore, Steven D.; Fenaux, Pierre; Prebet, Thomas.

In: Blood Advances, Vol. 2, No. 16, 28.08.2018, p. 2063-2071.

Research output: Contribution to journalArticle

Ball, B, Komrokji, RS, Adès, L, Sekeres, MA, Dezern, A, Pleyer, L, Vey, N, Almeida, A, Germing, U, Cluzeau, T, Platzbecker, U, Gore, SD, Fenaux, P & Prebet, T 2018, 'Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia', Blood Advances, vol. 2, no. 16, pp. 2063-2071. https://doi.org/10.1182/bloodadvances.2018015529
Ball, Brian ; Komrokji, Rami S. ; Adès, Lionel ; Sekeres, Mikkael A. ; Dezern, Amy ; Pleyer, Lisa ; Vey, Norbert ; Almeida, Antonio ; Germing, Ulrich ; Cluzeau, Thomas ; Platzbecker, Uwe ; Gore, Steven D. ; Fenaux, Pierre ; Prebet, Thomas. / Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia. In: Blood Advances. 2018 ; Vol. 2, No. 16. pp. 2063-2071.
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abstract = "Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients afterHMAfailure. Patients received 713, intermediate-to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens. For the MDS cohort (n 5 307), the overall response rate (ORR) was 41{\%}; median overall survival (OS) was 10.8 months, and 40{\%} of responding patients bridged to allogeneic stem cell transplant (allo-SCT). For the AML cohort (n 5 59), the ORR was 32{\%}, OS 6 months, and 42{\%} of responding patients bridged to allo-SCT. Prognostic factors for response in MDS included adverse cytogenetics (odds ratio [OR], 0.46, P 5 .01), age $65 years (OR, 0.47; P, .01), and use of IDAC (OR, 2.91, P 5 .01). Shorter survival was associated with adverse cytogenetics (hazard ratio [HR], 1.43; P 5 .06). In the AML cohort, OS was decreased by disease progression at time of HMA failure (HR, 2.66; P 5 .02) and prolonged with use of an anthracycline-containing regimen (HR, 0.37; P 5 .01). In conclusion, intensive chemotherapy after HMA failure may be a reasonable treatment option for selected patients as a bridge to allogeneic transplantation and should be considered a potential platform for future investigations.",
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T1 - Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia

AU - Ball, Brian

AU - Komrokji, Rami S.

AU - Adès, Lionel

AU - Sekeres, Mikkael A.

AU - Dezern, Amy

AU - Pleyer, Lisa

AU - Vey, Norbert

AU - Almeida, Antonio

AU - Germing, Ulrich

AU - Cluzeau, Thomas

AU - Platzbecker, Uwe

AU - Gore, Steven D.

AU - Fenaux, Pierre

AU - Prebet, Thomas

PY - 2018/8/28

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N2 - Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients afterHMAfailure. Patients received 713, intermediate-to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens. For the MDS cohort (n 5 307), the overall response rate (ORR) was 41%; median overall survival (OS) was 10.8 months, and 40% of responding patients bridged to allogeneic stem cell transplant (allo-SCT). For the AML cohort (n 5 59), the ORR was 32%, OS 6 months, and 42% of responding patients bridged to allo-SCT. Prognostic factors for response in MDS included adverse cytogenetics (odds ratio [OR], 0.46, P 5 .01), age $65 years (OR, 0.47; P, .01), and use of IDAC (OR, 2.91, P 5 .01). Shorter survival was associated with adverse cytogenetics (hazard ratio [HR], 1.43; P 5 .06). In the AML cohort, OS was decreased by disease progression at time of HMA failure (HR, 2.66; P 5 .02) and prolonged with use of an anthracycline-containing regimen (HR, 0.37; P 5 .01). In conclusion, intensive chemotherapy after HMA failure may be a reasonable treatment option for selected patients as a bridge to allogeneic transplantation and should be considered a potential platform for future investigations.

AB - Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients afterHMAfailure. Patients received 713, intermediate-to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens. For the MDS cohort (n 5 307), the overall response rate (ORR) was 41%; median overall survival (OS) was 10.8 months, and 40% of responding patients bridged to allogeneic stem cell transplant (allo-SCT). For the AML cohort (n 5 59), the ORR was 32%, OS 6 months, and 42% of responding patients bridged to allo-SCT. Prognostic factors for response in MDS included adverse cytogenetics (odds ratio [OR], 0.46, P 5 .01), age $65 years (OR, 0.47; P, .01), and use of IDAC (OR, 2.91, P 5 .01). Shorter survival was associated with adverse cytogenetics (hazard ratio [HR], 1.43; P 5 .06). In the AML cohort, OS was decreased by disease progression at time of HMA failure (HR, 2.66; P 5 .02) and prolonged with use of an anthracycline-containing regimen (HR, 0.37; P 5 .01). In conclusion, intensive chemotherapy after HMA failure may be a reasonable treatment option for selected patients as a bridge to allogeneic transplantation and should be considered a potential platform for future investigations.

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