RELATIVE BENEFIT FOR INTENSIVE VERSUS NON-INTENSIVE INDUCTION THERAPY FOR PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) USING A COMPOSITE, AGE-COMORBIDITY-CYTOGENETIC, MODEL
Author(s): ,
Mohamed Sorror
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States;University of Washington,Seattle,United States
,
Barry Storer
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States;University of Washington,Seattle,United States
,
Mahmoud Elsawy
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States
,
Amir Fathi
Affiliations:
Massachusetts General Hospital,Boston,United States
,
Andrew Brunner
Affiliations:
Massachusetts General Hospital,Boston,United States
,
Aaron Gerds
Affiliations:
Cleveland Clinic Taussig Cancer Institute,Cleveland,United States
,
Mikkael Sekeres
Affiliations:
Cleveland Clinic Taussig Cancer Institute,Cleveland,United States
,
Sudipto Mukherjee
Affiliations:
Cleveland Clinic Taussig Cancer Institute,Cleveland,United States
,
Bruno Medeiros
Affiliations:
Stanford University,Palo Alto,United States
,
Paul Shami
Affiliations:
University of Utah,Salt Lake City,United States
,
Esteban Pena
Affiliations:
University of Utah,Salt Lake City,United States
,
Shylo Wardyn
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States
,
Jennifer Whitten
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States
,
Pamela Becker
Affiliations:
Seattle Cancer Care Alliance,Seattle,United States;University of Washington,Seattle,United States
,
Jeannine McCune
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States;University of Washington,Seattle,United States
,
Stephanie Lee
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States;University of Washington,Seattle,United States
,
Brenda Sandmaier
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States;University of Washington,Seattle,United States
,
Frederick Appelbaum
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States;University of Washington,Seattle,United States
Elihu Estey
Affiliations:
Seattle Cancer Care Alliance,Seattle,United States;University of Washington,Seattle,United States
EHA Learning Center. Sorror M. Jun 11, 2016; 135337
Prof. Mohamed Sorror
Prof. Mohamed Sorror

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Abstract
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Abstract: LB580

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
Induction therapy for newly diagnosed AML can be classified as “more” or “less” intensive. Currently less intensive therapies such as azacitidine or decitabine (HMA) appear to be increasing in use among patients >65 years, reflecting concerns about the ability of older patients, who often have various comorbidities, to tolerate intensive therapy. However, the issue of relative efficacy of intense versus non- intense therapies arises together with the question about the relative benefit/risk ratios of these options in various populations defined by age, comorbidities, and disease-related characteristics such as cytogenetic and molecular features.

Aims
Our group has designed and validated a new model combining the prognostic effects of age, comorbidity index, and cytogenetic/molecular risks (Blood 2015 126:532). Here, we used this composite model to define distinct prognostic groups and within each, compared two year mortality rates among patients with newly-diagnosed AML according to whether they received intensive or non-intensive therapy at 5 collaborating institutions. Non-intensive therapy principally included HMA or low-dose cytarabine, while intensive therapies primarily consisted of “7+3” or other similar cytotoxic induction regimens.

Methods
We retrospectively collected information regarding comorbidities, laboratory, and survival data from 1079 patients with newly diagnosed AML who received therapy at 5 institutions from 20082012. Median follow-up of patients still alive was 30 months.

Results
Patients were ≤49 (29%), 50-59 (25%), 60-69 (26%), and ≥70 (20%) years old. Cytogenetic-molecular risks were favorable (21%), intermediate I and II (36%), or unfavorable (43%) per European Leukemia Net classification. Induction treatments were non-intensive in 18% and intensive in 81% of patients. Using the composite risk model, 17% of patients had scores of 2-4, 37% scores 5-7, 27% scores 8-10, and 19% scores ≥11. As shown before (Blood 2015 126:532), hazard ratios (HR) for mortality increased with increasing scores.Patients with the lowest scores (2-4) almost always received intensive therapies (98%), and were therefore omitted from the comparison analysis. Table 1 shows distribution of regimen intensity per patient age groups: the proportion of patients receiving non-intensive therapy increased with increasing age. Patients with scores 5-7, 8-10, and ≥11 had statistically significantly higher survival rates when given intensive versus non-intensive therapies (Table 2). We also looked at outcomes specifically among patients 70-79 years old given intensive (46%) or non-intensive (54%) therapies. Intensive therapies among those older patients resulted in statistically significantly higher survival rates at 2-year (27% versus 11%, HR: 0.72, P=0.05, Figure).

Conclusion
Intensive therapy leads to better long term survival even in older patients with significant co-morbidities. Early mortality is not increased in older patients given intensive rather than non-intensive induction therapy, likely due to improvements in supportive care over time.  While we cannot exclude the effects of selection bias, our model accounted for the principal covariates associated with outcome. Absent a randomized trial comparing intensive and non- intensive therapies, our results suggest that the former should be offered to all patients up to the age of 80 regardless of their comorbidity burden. Prospective randomized studies are needed to investigate the role of non-intensive therapies in older patients in light of their comorbidity burden. Studies of physical, cognitive, and social health might further identify groups of patients for whom non-intensive therapies could yield survival benefit.



Session topic: Acute myeloid leukemia - Clinical 3

Keyword(s): Acute myeloid leukemia, Comorbidities, Induction chemotherapy, Prognostic groups
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