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. 2020 Apr 28;4(8):1690-1699.
doi: 10.1182/bloodadvances.2019001150.

Clinical value of event-free survival in acute myeloid leukemia

Abhishek Maiti  1   2 , Hagop M Kantarjian  1 , Vinita Popat  1   3 , Gautam Borthakur  1 , Guillermo Garcia-Manero  1 , Marina Y Konopleva  1 , Courtney D DiNardo  1 , Srdan Verstovsek  1 , Michael Andreeff  1 , Tapan M Kadia  1 , Helen O Ajufo  4 , Rohit V Goswamy  4 , Carlos Blanco  1 , Miguel Velasquez  1 , Naval G Daver  1 , Naveen Pemmaraju  1 , Sherry R Pierce  1 , William G Wierda  1 , Steven M Kornblau  1 , Farhad Ravandi  1 , Jorge E Cortes  1   5
Affiliations

Clinical value of event-free survival in acute myeloid leukemia

Abhishek Maiti et al. Blood Adv. .

Abstract

The value of event-free survival (EFS) as an end point in acute myeloid leukemia (AML) trials has been questioned. We hypothesized that rather than a surrogate for overall survival (OS), improvement in EFS may decrease the use of health care. In this retrospective study, we identified 400 patients with AML who were treated on first-line therapy trials and had OS between 2 and 36 months. We captured health care use from diagnosis until death or until the patient was censored at stem cell transplantation (SCT). We used correlation and regression analysis to determine the relation between health care use and EFS. Among patients with newly diagnosed AML, 35% had adverse-risk AML, 48% received intensive chemotherapy, and 28% received hypomethylating agents. The median EFS censored at SCT was 9.7 months. Longer EFS led to a significant decline in health care use regardless of OS. This held true for all observations, including overall health care use (r = -0.45), sum of clinic visits, emergency room visits, hospitalizations, consultations (r = -0.44), sum of invasive procedures, laboratory and imaging studies (r = -0.51), and blood product transfusions (r = -0.19). These correlations were stronger for patients who achieved a complete remission and held true across age, treatment, and disease risk subgroups. In patients with newly diagnosed AML, improvement in EFS correlates with a decrease in all health care use irrespective of OS duration.

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Conflict of interest statement

Conflict-of-interest disclosure: A.M. received research funding from Celgene. H.M.K. received honoraria and research funding from Pfizer, ARIAD, Bristol-Myers Squibb, and Amgen, honoraria from Orsenix, Immunogen, Actinium, and AbbVie, and research funding from Novartis and Astex. M.Y.K. received research funding from Stemline Therapeutics. S.V. received research funding from Genentech, Lilly Oncology, NS Pharma, CTI BioPharma, Incyte, Seattle Genetics, Blueprint Medicines, Celgene, Pfizer, Roche, AstraZeneca, Bristol-Myers Squibb, Promedior, Galena BioPharma, and Gilead. M.A. received research funding from AstraZeneca. H.M.K. received honoraria and research funding from Pfizer, Bristol-Myers Squibb, ARIAD, and Amgen, honoraria from Orsenix, Immunogen, Actinium, and AbbVie, and research funding from Novartis and Astex. T.M.K. has served as a consultant for and received research funding from Amgen, Jazz Pharmaceuticals, and Pfizer, served as a consultant for Takeda, Novartis, and AbbVie, and received research funding from Celgene and Bristol-Myers Squibb. N.G.D. served as a consultant for and received research funding from Incyte, Daiichi-Sankyo, ImmunoGen, Karyopharm, Bristol-Myers Squibb, Pfizer, and Novartis, served as a consultant for Sunesis, Alexion, and Otsuka, and has received research funding from Pfizer, Novartis, Kiromic, and ARIAD. N.P. served as a consultant for and received honoraria from Celgene, and has served as a consultant for and received honoraria and research funding from Stemline. C.D.D. served as a consultant and adviser for AbbVie and Agios, as an adviser for Bayer, Celgene, Medimmune, and Karyopharm, and received research funding from Plexxikon, Novartis, Affymetrix, Samus, Cellectis, SagerStrong Foundation, AbbVie, and Daiichi Sankyo. W.G.W. received research funding from AbbVie and Genentech. F.R. has received honoraria and research funding from and served on the Speakers Bureau for Amgen, has received honoraria from Jazz Pharmaceuticals, Sunesis, and Orsenix, has received research funding from AbbVie, Xencor, Bristol-Myers Squibb, and Seattle Genetics, has received honoraria and research funding from Macrogenix, and has served as a consultant for and received honoraria from Astellas Pharmaceuticals. J.E.C. has received research funding from Amphivena, Arog, Astellas Pharma, Bristol-Myers Squibb, Celgene, Daiichi-Sankyo, Immunogen, Jazz Pharmaceuticals, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Teva, and Rafael, and has served as a consultant for Astellas Pharma, BiolineRx, Biopath Holdings, Bristol-Myers Squibb, Daiichi-Sankyo, Novartis, Pfizer, Takeda, and Jazz Pharmaceuticals (all to the institution). The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Correlation between increasing EFS and decreasing use of health care for all patients. Overall use of health care per month of OS (A), combined clinic visits, ER visits, hospitalizations, and consultations per month of OS (B), combined invasive procedures, imaging, and laboratory studies per month of OS (C), and blood product transfusions per month of OS (D). Overall use of health care consisted of the sum of the number of clinic visits, ER visits, hospital admissions, consultations, blood product transfusions, laboratory studies, imaging studies, and invasive procedures. Blood product transfusions included packed red blood cell and platelet transfusions.
Figure 2.
Figure 2.
Correlation between increasing EFS and decreasing use of health care in 286 patients achieving a complete response. Correlation with overall use of health care per month of OS (A), combined clinic visits, ER visits, hospitalizations, and consultations per month of OS (B), combined invasive procedures, imaging, and laboratory studies per month of OS (C), blood product transfusions per month of OS (D), hospitalizations per month (E), and ER visits per month (F).
Figure 3.
Figure 3.
Correlation between increasing EFS and decreasing overall use of health care per month of OS. Among patients with ELN intermediate-risk AML (A), ELN adverse-risk AML (B), age <65 years (C), age ≥65 years (D), receiving intensive chemotherapy with or without other non-chemotherapy agents (E), and receiving hypomethylating agents with or without other non-chemotherapy agents (F).
Figure 4.
Figure 4.
Linear correlation and nonlinear fit between increasing EFS and decreasing use of health care per month of EFS for all patients. Overall use of health care per month of EFS (A), combined clinic visits, ER visits, hospitalizations, and consultations per month of EFS (B), combined invasive procedures, imaging, and laboratory studies per month of EFS (C), and blood product transfusions per month of EFS (D). (E) Use of health care in patients grouped according to increasing EFS. The decline in use of health care between patients with EFS of 1 to 6 months, >6 to 12 months, and >12 to 18 months was highly statistically significant. (F) Trend of overall use of health care with increasing EFS in patients grouped according to narrow OS ranges. Overall use of health care consisted of the sum of the number of clinic visits, ER visits, hospital admissions, consultations, blood product transfusions, laboratory studies, imaging studies, and invasive procedures. Blood product transfusions included packed red blood cell and platelet transfusions.
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