Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease

Christopher S. Hourigan; Laura W. Dillon; Gege Gui; Brent R. Logan; Mingwei Fei; Jack Ghannam; Yuesheng Li; Abel Licon; Edwin P. Alyea; Asad Bashey; H. Joachim Deeg; Steven M. Devine; Hugo F. Fernandez; Sergio Giralt; Mehdi Hamadani; Alan Howard; Richard T. Maziarz; David L. Porter; Bart L. Scott; Erica D. Warlick; Marcelo C. Pasquini; Mitchell E. Horwitz

doi:10.1200/JCO.19.03011

Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease

Christopher S. Hourigan, Laura W. Dillon, Gege Gui, Brent R. Logan, Mingwei Fei, Jack Ghannam, Yuesheng Li, Abel Licon, Edwin P. Alyea, Asad Bashey, H. Joachim Deeg, Steven M. Devine, Hugo F. Fernandez, Sergio Giralt, Mehdi Hamadani, Alan Howard, Richard T. Maziarz, David L. Porter, Bart L. Scott, Erica D. WarlickMarcelo C. Pasquini, Mitchell E. Horwitz

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

295 Scopus citations

Abstract

PURPOSE: Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown.

METHODS: Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC).

RESULTS: No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive.

CONCLUSION: This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

Original language	English (US)
Pages (from-to)	1273-1283
Number of pages	11
Journal	Journal of Clinical Oncology
Volume	38
Issue number	12
DOIs	https://doi.org/10.1200/JCO.19.03011
State	Published - Apr 20 2020

Bibliographical note

Funding Information:
Supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and by Grant No. U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from NHLBI and the National Cancer Institute. This study used BMT CTN 0901 research materials, biospecimens, and clinical trial data provided by the BMT CTN. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2019 by American Society of Clinical Oncology

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Research Support, N.I.H., Intramural
Journal Article
Research Support, N.I.H., Extramural

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Hourigan, C. S., Dillon, L. W., Gui, G., Logan, B. R., Fei, M., Ghannam, J., Li, Y., Licon, A., Alyea, E. P., Bashey, A., Deeg, H. J., Devine, S. M., Fernandez, H. F., Giralt, S., Hamadani, M., Howard, A., Maziarz, R. T., Porter, D. L., Scott, B. L., ... Horwitz, M. E. (2020). Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. Journal of Clinical Oncology, 38(12), 1273-1283. https://doi.org/10.1200/JCO.19.03011

Hourigan, CS, Dillon, LW, Gui, G, Logan, BR, Fei, M, Ghannam, J, Li, Y, Licon, A, Alyea, EP, Bashey, A, Deeg, HJ, Devine, SM, Fernandez, HF, Giralt, S, Hamadani, M, Howard, A, Maziarz, RT, Porter, DL, Scott, BL, Warlick, ED, Pasquini, MC & Horwitz, ME 2020, 'Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease', Journal of Clinical Oncology, vol. 38, no. 12, pp. 1273-1283. https://doi.org/10.1200/JCO.19.03011

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title = "Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease",

abstract = "PURPOSE: Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown.METHODS: Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC).RESULTS: No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION: This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.",

author = "Hourigan, {Christopher S.} and Dillon, {Laura W.} and Gege Gui and Logan, {Brent R.} and Mingwei Fei and Jack Ghannam and Yuesheng Li and Abel Licon and Alyea, {Edwin P.} and Asad Bashey and Deeg, {H. Joachim} and Devine, {Steven M.} and Fernandez, {Hugo F.} and Sergio Giralt and Mehdi Hamadani and Alan Howard and Maziarz, {Richard T.} and Porter, {David L.} and Scott, {Bart L.} and Warlick, {Erica D.} and Pasquini, {Marcelo C.} and Horwitz, {Mitchell E.}",

note = "Funding Information: Supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and by Grant No. U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from NHLBI and the National Cancer Institute. This study used BMT CTN 0901 research materials, biospecimens, and clinical trial data provided by the BMT CTN. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2019 by American Society of Clinical Oncology",

year = "2020",

month = apr,

day = "20",

doi = "10.1200/JCO.19.03011",

language = "English (US)",

volume = "38",

pages = "1273--1283",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "12",

}

TY - JOUR

T1 - Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease

AU - Hourigan, Christopher S.

AU - Dillon, Laura W.

AU - Gui, Gege

AU - Logan, Brent R.

AU - Fei, Mingwei

AU - Ghannam, Jack

AU - Li, Yuesheng

AU - Licon, Abel

AU - Alyea, Edwin P.

AU - Bashey, Asad

AU - Deeg, H. Joachim

AU - Devine, Steven M.

AU - Fernandez, Hugo F.

AU - Giralt, Sergio

AU - Hamadani, Mehdi

AU - Howard, Alan

AU - Maziarz, Richard T.

AU - Porter, David L.

AU - Scott, Bart L.

AU - Warlick, Erica D.

AU - Pasquini, Marcelo C.

AU - Horwitz, Mitchell E.

N1 - Funding Information: Supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and by Grant No. U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from NHLBI and the National Cancer Institute. This study used BMT CTN 0901 research materials, biospecimens, and clinical trial data provided by the BMT CTN. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: © 2019 by American Society of Clinical Oncology

PY - 2020/4/20

Y1 - 2020/4/20

N2 - PURPOSE: Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown.METHODS: Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC).RESULTS: No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION: This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

AB - PURPOSE: Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown.METHODS: Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC).RESULTS: No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION: This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

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DO - 10.1200/JCO.19.03011

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SN - 0732-183X

VL - 38

SP - 1273

EP - 1283

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 12

ER -

Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease

Abstract

Bibliographical note

PubMed: MeSH publication types

UN SDGs

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