Unique Clinical Trial Leads to Dramatic Decrease in Early Deaths from Rare and Aggressive, Yet Highly Curable Acute Promyelocytic Leukemia (APL)

Unique Clinical Trial Leads to Dramatic Decrease in Early Deaths from Rare and Aggressive, Yet Highly Curable Acute Promyelocytic Leukemia (APL)

Dr Anand Jillella

Image: Dr. Anand Jillella
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Credit: Augusta University

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, has resulted in a dramatic decrease in early deaths from acute promyelocytic leukemia (APL). The discovery comes from a prospective multicenter trial by the ECOG-ACRIN cancer research group (study EA9131). The primary goal was to reduce induction mortality (days 2-35) from approximately 30% to 15% or less. The EA9131 study met its primary objective, with a mortality rate of only 3.5%.

Principal Investigator Anand P. Jillella, MDpresented the unique collaborative care model today at the American Society of Hematology (ASH) 64th Annual Meeting and Exposition in New Orleans.

“A standardized algorithm with expert support decreases early APL deaths and increases overall survival,” said Dr. Jillella, a medical oncologist and APL expert at the Georgia Cancer Center and the Medical College of Georgia at Augusta University. “Most oncologists currently do not have access to simplified care instructions and institutional pathways for management recommendations aimed at improving patient outcomes.”

APL, a subtype of acute myeloid leukemia (AML), is extremely rare, with only about 3,000 new cases per year in the United States. Also, the treatment differs from the treatment of most other types of AML. As a result, many providers do not know how to treat this disease.

Prompt diagnosis and treatment of APL is essential because patients can quickly develop life-threatening blood clotting or bleeding problems if not treated urgently. With advances in the past decade, arsenic trioxide and non-chemotherapeutic drugs called differentiating agents, such as all-trans-retinoic acid (ATRA), are now standard treatments for APL. These treatments are very effective; however, the early mortality rate in PLA is high up to 30%.

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

The three most common causes of early death during the induction period are bleeding, infection, and differentiation syndrome, the latter being caused by complications that develop as a result of treatment. Other risk factors for mortality include advanced age (over 60), comorbid conditions, particularly obesity, and the complexity of LAP at presentation.

“In my opinion, many early deaths from APL are preventable, and I don’t think there’s a good reason most of these patients die,” said Dr Jillella. “The involvement of clinicians familiar with potential complications is essential.”

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. A total of 202 patients enrolled in the trial; 62 at six major academic centers and 140 at 37 community hospitals through the National Cancer Institute (NCI) Community Oncology Research Program (NCORP).

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

“Clinical trials for APL tend to enroll younger patients without comorbid conditions, whereas the general APL patient population tends to be older and with comorbidities,” said Dr. Jillella. “However, since many patients present to hospitals where doctors are unfamiliar with the intricacies of managing APL, they may benefit from the advice of someone more experienced.”

Seven deaths (3.5%) occurred during the induction period, all due to differentiation syndrome, including four at primary centers and three at community sites. Six of the seven deaths were in the elderly (69-91 years old).

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

“Dr. Jillella has demonstrated that by providing guidance, we can truly optimize care and prevent early death in patients with APL,” said ECOG-ACRIN Leukemia Committee Chair Selina M. Luger, MDthe study’s APL expert at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

“This model provides us with a framework to improve the care of patients with other complex diseases who cannot participate in clinical trials or attend academic medical centers, even if they have limited resources or significant medical comorbidities. .”

The trial was funded by the Cancer Prevention Division of the National Cancer Institute, part of the National Institutes of Health.

“Based on these results, we are evaluating other ways to provide guided assistance to patients with complicated and treatment leukemias,” said Dr AS Luger. “Additionally, the results of this study provided insight into treatment modifications for APL patients with significant comorbidities that allow them to achieve remission without additional toxicities.”

Summary 421 – A simplified patient management strategy to reduce early deaths in acute promyelocytic leukemia (APL): results from the ECOG-ACRIN EA9131 trial, part of Session 613.

ClinicalTrials.gov ID: NCT03253848.

About the Collaborative Care Plan

After successful pilot testing at NCORP community sites in Georgia and South Carolina, with Dr. Jillella and a colleague serving as APL experts, he presented the program to the ECOG-ACRIN Leukemia Committee, of which he is a member. Together they developed EA9131 in a prospective trial.

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

In the main centres, the referring oncologists managed their patients with input from the local expert. At community centers, oncologists contacted one of seven experts as soon as a patient presented with suspected APL by email or phone. Expert assistance was available 24 hours a day, 7 days a week, and the patient was eligible for enrollment if there was contact with APL experts within 72 hours of starting treatment .

The experts provided an initial workup suggestion and treatment plan to the treating physician, then maintained communication throughout the induction. Treatment recommendations followed the standard of care, but dose reductions were suggested for advanced age and comorbidities. For patients with more complex medical issues, the seven experts would often discuss the case and make a consensus recommendation.


The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. ECOG-ACRIN includes nearly 1,300 member institutions in the United States and around the world. Around 15,000 physicians, translational researchers and associate research professionals from member institutions are involved in the Group’s research. For more information, visit http://www.ecog-acrin.org, follow us on Twitter @eaonc, Facebook and LinkedIn, or call 215.789.3631.


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