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. 2025 Feb 27;11(4):400-407.
doi: 10.1001/jamaoncol.2024.7033. Online ahead of print.

Academic Community Partnership in Acute Promyelocytic Leukemia and Early Mortality: The ECOG-ACRIN EA9131 Trial

Anand P Jillella  1 , Sandra J Lee  2 , Jessica K Altman  3 , Selina M Luger  4 , Martin S Tallman  3 , James M Foran  5 , Danielle Bradshaw  1 , Lisa Y Law  6 , Locke J Bryan  1 , Abdallah Abou Zahr  7 , Kebede H Begna  5 , Alexander E Perl  4 , Joseph J L Vadakara  8 , Rubina Qamar  9 , Raymond C Bergan  10 , Michael J Fisch  11 , Ruth C Carlos  12 , Lynne I Wagner  13 , Vamsi K Kota  1 , Mark R Litzow  5
Affiliations

Academic Community Partnership in Acute Promyelocytic Leukemia and Early Mortality: The ECOG-ACRIN EA9131 Trial

Anand P Jillella et al. JAMA Oncol. .

Abstract

Importance: Acute promyelocytic leukemia (APL) is an acute illness that presents with cytopenia, infections, and disseminated intravascular coagulation. Achieving remission has been shown to make a major difference in patient outcomes; however, early death rates in the first month have been as high as 30% due to acute presentation, comorbidities, the rarity of APL, and clinician inexperience.

Objective: To develop treatment strategies that would decrease estimated 1-month mortality from 30% to below 15%.

Design, setting, and participants: In this nonrandomized clinical trial, a treatment algorithm that focused on supportive care was used to prevent early death in patients with APL treated at academic and community health centers between August 2017 and July 2021. Because of the rarity of the disease, expert support was available 24/7 from 7 designated APL experts at 6 participating academic lead centers, and included an additional 293 community centers. When a patient presented with APL, an expert was contacted and a consensus treatment plan was developed using the algorithm and expert suggestions. There were no exclusion criteria and all patients with a confirmed diagnosis of APL regardless of age or comorbid conditions were enrolled. Expert support was provided throughout induction. Initial data analysis was conducted May 2023.

Main outcomes and measures: One-month mortality; additional objectives were to compare outcomes in academic and community centers and assess 1-year and overall survival.

Results: A total of 201 patients were enrolled from 43 centers; 62 at lead centers and 139 from 37 community centers. The median age was 53 years (range, 18-91 years), with 72 patients (35.8%) who were aged 60 years or older; 105 patients (52.2%) were male. Fifty-two patients (26.4%) were diagnosed with high-risk APL. The 1-month mortality rate was 6 deaths of 201 patients (3.0%; 95% CI, 1.1%-6.4%) after adjusting for 1 interim analysis. In a secondary analysis using the Kaplan-Meier method, the 1-month overall survival (OS) rate was 97.0% (95% CI, 93.5%-98.6%) and the 1-year OS rate was 94.5% (95% CI, 90.3%-96.9%).

Conclusions and relevance: In this nonrandomized clinical trial, use of an algorithm combined with expert support resulted in a dramatic decrease in early death in academic and community centers. Population-wide survival improved in this highly curable disease, which suggests that implementing an accessible support system with APL experts for comanagement is the most logical next step.

Trial registration: ClinicalTrials.gov Identifier: NCT03253848.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Altman reported receiving personal fees from Glycomimetics DMC, Kura Oncology, Abbvie, Ascentage, Astellas, BioSight, BlueBird, Curio, Daiichi Sankyo, Dark Blue Therapeutics, Gilead, Kymera, Rigel, Stemline Therapeutics, Syros, Treadwell Therapeutics, HMP Global, MD Education, National Cancer Institute (NCI), personal fees from National Comprehensive Cancer Network, PeerView, Physicians Education Resource, VJ HemOnc, Syndax, and Onviv outside the submitted work. Dr Tallman reported receiving personal fees for service on an advisory board for Moleculin Biotech; he reported nonfinancial support for committee work with Foghorn and data safety monitoring board work for the HOVON HO156 trial; he reported royalties with UpToDate; and he reported personal fees for conducting grand rounds from Northwestern University Medicine, MetroHealth Medical Center, and Ohio State University Cancer Center outside the submitted work. Dr Foran reported receiving personal fees from Astellas, Syndax, Treadwell Therapeutics, Bristol-Myers Squibb; he reported receiving grants from Kura Oncology and Sellas outside the submitted work; and he reported ownership of publicly traded stock in Aurinia Pharmaceuticals. Dr Perl reported grants from Astellas, Daiichi Sankyo, Abbvie, and Syndax paid to his institution; he reported receiving personal fees from Astellas, Daiichi Sankyo, Foghorn, Beat AML, LLC, Abbvie, Genentech, Rigel, Bristol-Myers Squibb, Schrodinger, Aptose, Curis, Immunogen, BerGenBio, and Syndax outside the submitted work. Dr Vadakara reported receiving honoraria from Dava Oncology and Curio Science outside the submitted work. Dr Carlos reported receiving grants from ECOG-ACRIN during the conduct of the study; and she reported receiving salary support as the Editor in Chief of Journal of the American College of Radiology. Dr Wagner reported consulting fees from Celgene/Bristol-Myers Squibb, Myeloma registry PRO analysis outside the submitted work. Dr Kota reported receiving personal fees from Novartis and Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Trial Flowchart
APL indicates acute promyelocytic leukemia; NCORP, National Cancer Institute Community Oncology Research Program. aOne patient was excluded from analysis due to a registration error and 1 patient withdrew consent. No patients were excluded on enrollment.
Figure 2.
Figure 2.. Kaplan-Meier Plot of Survival Probability of Study Patients
See this image and copyright information in PMC

Comment in

  • doi: 10.1001/jamaoncol.2024.6649

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