Simplified Treatment Regimen Reduces Early Deaths in Patients With APL

Get Permission

The use of a simplified treatment regimen by oncologists—along with management recommendations and 24/7 support provided by a limited and dedicated group of academic disease experts—resulted in a decrease in early deaths from acute promyelocytic leukemia (APL). In the multicenter prospective trial Study EA9131, led by the ECOG-ACRIN Cancer Research Group, the primary aim was to decrease induction (days 2–35) mortality from an estimated 30% to 15% or less. The study met its primary objective, with a mortality rate of only 3.5%. Lead researcher Anand P. Jillella, MD, presented the unique collaborative care model at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 421).

"A standardized algorithm with expert support decreases early deaths from APL and increases overall survival," said Dr. Jillella, a medical oncologist and APL expert at the Georgia Cancer Center and Medical College of Georgia at Augusta University. "Most oncologists currently lack access to simplified care instructions and institutional pathways for management recommendations to improve patient outcomes."

Anand P. Jillella, MD

Anand P. Jillella, MD

Study Background

APL, a subtype of acute myeloid leukemia (AML), is extremely rare, with only about 3,000 new cases annually in the United States. In addition, its treatment differs from the treatment of most other types of AML. As a result, many providers lack familiarity with how to effectively treat patients with APL.

Prompt diagnosis and treatment of APL are critical because patients can quickly develop life-threatening blood clotting or bleeding problems if not treated emergently. With advances over the last decade, arsenic trioxide and nonchemotherapy drugs called differentiating agents, like all-trans retinoic acid (ATRA), are now the standard APL treatments. These treatments are highly effective; however, the early death rate in APL is high, at up to 30%.

"With our current therapies, APL, previously one of our deadliest leukemias, is now curable, and when that happens, people maintain their quality of life and go back to doing what they used to do. But these treatments cause side effects that are not typical of standard chemotherapy and can lead to death. Since most deaths from APL occur in the first 30 days of treatment, if patients survive the first month, it's a home run," said Dr. Jillella.

The EA9131 Collaborative Care Model

The EA9131 collaborative care model provided contact with a disease expert who suggested ways to adjust or personalize standard treatment based on the patient's disease status and risk factors.

After a successful pilot test at National Cancer Institute (NCI) Community Oncology Research Program (NCORP) community sites in Georgia and South Carolina, Dr. Jillella brought the program to the ECOG-ACRIN Leukemia Committee, where he is a member. Together, they developed EA9131 as a prospective trial.

There were seven academic APL experts at six lead academic centers. They include the Mayo Clinic in Minnesota; Mayo Clinic in Jacksonville, Florida; Medical College of Georgia; Memorial Sloan Kettering Cancer Center; Northwestern University; and the University of Pennsylvania's Abramson Cancer Center.

At the lead centers, the treating oncologists managed their patients with input from the local expert. At the community centers, oncologists contacted one of the seven experts as soon as a patient presented with suspected APL by email or phone. Expert support was available 24/7, and the patient was eligible for enrollment if there was contact with the APL experts within 72 hours of initiating therapy.

The experts provided a suggested initial work-up and treatment plan to the treating physician, then maintained communication throughout induction. Therapy recommendations followed the standard of care, but dose reductions were suggested for older age and comorbidities. For patients with more complex medical issues, all seven experts often discussed the case and made a consensus recommendation.

A total of 202 patients enrolled in the trial; 62 at 6 academic centers and 140 at 37 community hospitals through NCORP.

There were no exclusions for eligibility based on patient age or general health status.

"Clinical trials for APL tend to enroll younger patients with no comorbid conditions, whereas the general population of [patients with] APL tends to be elderly and [have] comorbidities," said Dr. Jillella. "However, since many patients present to hospitals where the doctors are not familiar with the intricacies of managing APL, they can benefit from the guidance of someone with more experience."

Rates of Mortality

Seven deaths (3.5%) occurred during the induction period, all due to differentiation syndrome, with four at lead centers and three at community sites. Six of seven deaths were among the elderly (range = 69–91 years).

One-year survival was 94.5%, with no difference between patients treated at academic and community centers.

Selina M. Luger, MD

Selina M. Luger, MD

"Dr. Jillella has demonstrated that by providing guidance, we can truly optimize the care of and prevent early deaths in [patients with] APL," said ECOG-ACRIN Leukemia Committee Chair Selina M. Luger, MD, the study's APL expert at the University of Pennsylvania’s Abramson Cancer Center. "This model provides us with a framework to enhance the care of patients with other complex diseases who cannot participate in clinical trials or travel to academic medical centers even if they have limited resources or significant medical comorbidities."

"Based on these results, the study team is evaluating other ways to provide guided assistance for patients with complicated leukemias and treatment," continued Dr. Luger. "Additionally, results of this study have provided insight into treatment modifications for [patients with] APL with significant comorbidities that allow them to achieve remission without additional toxicities."

Disclosure: The trial was funded by the Division of Cancer Prevention at the National Cancer Institute, part of the National Institutes of Health. For full disclosures of the study authors, visit


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.