Page 86 - 2021_06-Haematologica-web

Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2114-2120
Acute Myeloid Leukemia
Survival of patients with newly diagnosed high-grade myeloid neoplasms who do not meet standard trial eligibility
Mary-Elizabeth M. Percival,1,2 Megan Othus,3 Sarah Mirahsani,1
Kelda M. Gardner,1 Carole Shaw,2 Anna B. Halpern,1,2 Pamela S. Becker,1,2 Paul C. Hendrie,1 Mohamed L. Sorror,2,4 Roland B. Walter1,2
and Elihu H. Estey1,2
1Division of Hematology, Department of Medicine, University of Washington; 2Clinical Research Division, Fred Hutchinson Cancer Research Center; 3Public Health Sciences, Fred Hutchinson Cancer Research Center and 4Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
ABSTRACT
Few patients with cancer, including those with acute myeloid leukemia and high-grade myeloid neoplasms, participate in clinical trials. Broadening standard eligibility criteria may increase clinical trial participation. In this retrospective single-center analysis, we identi- fied 442 consecutive newly diagnosed patients from 2014 to 2016. Patients were considered “eligible” if they had a performance status 0-2, normal renal and hepatic function, no recent solid tumor, left ventricular ejection fraction (EF) ≥50%, and no history of congestive heart failure (CHF) or myocardial infarction (MI); “ineligible” patients failed to meet one or more of these criteria. We included 372 patients who received chemotherapy. Ineligible patients represented 40% of the population and had a 1.79-fold greater risk of death (95% Confidence Interval [CI]: 1.37-2.33) than eligible patients. Very few patients had cardiac comor- bidities, including 2% with low EF, 4% with prior CHF, and 5% with prior MI. In multivariable analysis, ineligibility was associated with decreased survival (Hazard ratio [HR] 1.44; 95% CI: 1.07-1.93). Allogeneic transplantation, performed in 150 patients (40%), was associ- ated with improved survival (HR 0.66, 95% CI: 0.48-0.91). Therefore, standard eligibility characteristics identify a patient population with improved survival. Further treatment options are needed for patients considered ineligible for clinical trials.
Introduction
National Comprehensive Cancer Network guidelines state “the best manage- ment of any patient with cancer is in a clinical trial.” Nonetheless, relatively few adults with cancer participate in clinical trials.1 Preferences of patients and physi- cians, and the distances separating patients from an academic center, undoubted- ly contribute and are probably not amenable to change. In contrast, protocol eligi- bility criteria may be more flexible. These are often stereotypical, ignoring the complexity and individualized nature of clinical care. Oncology clinical trials, par- ticularly those sponsored by industry, are generally written with standard eligibil- ity (and ineligibility) criteria which if anything are becoming more stringent over time.2 The American Society of Clinical Oncology (ASCO) and similar groups have encouraged broader eligibility criteria, thus increasing the relevance of clini- cal trial results for the great majority of patients who do not participate in trials.3
An analysis by Lichtman et al., published simultaneously with the ASCO recom- mendations, found 50-85% of over 10,000 patients with breast, colorectal, lung, or bladder cancer seen in 2013 and 2014 at Kaiser Permanente Northern California would not meet standard clinical trial eligibility criteria.4 This analysis defined eli- gibility as meeting the requirements of younger age, relatively normal heart, kid- ney, and liver function, and no recent solid tumor. While some investigational
Correspondence:
MARY-ELIZABETH M. PERCIVAL
mperciva@uw.edu
Received: April 6, 2020. Accepted: July 6, 2020. Pre-published: July 9, 2020.
https://doi.org/10.3324/haematol.2020.254938
©2021 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
2114
haematologica | 2021; 106(8)
ARTICLE