Anand P. Jillella, MD, on Acute Promyelocytic Leukemia: A Simplified Patient Care Strategy to Decrease Early Deaths
2022 ASH Annual Meeting and Exposition
Anand P. Jillella, MD, of Georgia Cancer Center at Augusta University, discusses results from the ECOG-ACRIN EA9131 Trial, which showed that using a simplified treatment algorithm and management recommendations made by a group of specialists, resulted in a dramatic improvement in 1-year survival of patients with acute promyelocytic leukemia (Abstract 421).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Acute promyelocytic leukemia is a highly aggressive but very curable leukemia. The current standard of care is all-trans retinoic acid and arsenic trioxide with or without chemotherapy. In clinical trials, about 95% to 98% of patients are cured. The induction death or early death, which is death within the first 30 days after diagnosis, is under 5%, and the relapse rate is less than 2%. So virtually everyone who survives induction is cured of their leukemia. However, that is not the case in the general population because in clinical trials the patients are usually younger and do not have any comorbid conditions. Whereas in the general population, you have older patients who might have other health issues. About 30% of patients do not survive induction or die during the first month after diagnosis. The one-year survival among all comers is about 60% to 70%.
The only way to decrease survival among the general population is to decrease early deaths. The purpose of the ECOG-ACRIN 9131 trial was to decrease the induction mortality from an estimated 30% to less than 15%.
At the Medical College of Georgia, in Augusta, Georgia, we recognized this as a problem way back in 2009. We evaluated our own experience and realized that 37% of our patients died within the first month after diagnosis. So we critically analyzed the problem and came up with a plan to decrease early deaths. Number one, we wrote a treatment algorithm or an operating procedure, which is a simplified procedure that tells you exactly how you have to manage the patient and the complications. The second thing is it is a rare disease, so we set up a panel of four experts. If there was a patient with APL in the community, the community oncologist would call one of the experts. The expert and the community oncologist would determine a consensus treatment plan, and the patient would be treated locally in the community but with ongoing communication with the APL expert. In this pilot trial, we accrued 120 patients. We had an early death rate of 8.5%.
We used a similar model in the ECOG-ACRIN 9131 trial. We used the same algorithm. We set up seven APL experts who were available 24/7, and we rolled it out nationwide. There were absolutely no exclusion criteria. Elderly patients or patients with other health issues were recruited into the trial. A total of 200 patients were accrued, and we had seven deaths, which is an early death rate of 3.5%. As best as I know, this is the only proven concept that decreases early deaths in APL. This concept has also been proven in Latin America. The next steps would be to find a way to scale this and find a sustainable way to implement this nationwide.
Tomohiro Aoki, MD, PhD, of the University of British Columbia and the Centre for Lymphoid Cancer at BC Cancer, discusses a novel prognostic model applicable to patients with relapsed or refractory classical Hodgkin lymphoma who were treated with autologous stem cell transplantation. The model has shown the interaction between the biomarker CXCR5 on HRS cells (Hodgkin and Reed/Sternberg cells, hallmarks of Hodgkin lymphoma) with specific follicular T helper cells and macrophages, a prominent crosstalk axis in relapsed disease. This insight opens new avenues to developing predictive biomarkers (Abstract 71).
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, discusses preliminary results from the dose-expansion phase of the CC-92480-MM-001 Trial, which showed promising efficacy in patients with relapsed and refractory multiple myeloma, including those with prior BCMA-targeted therapies. Patients in these two groups had an overall response rate of 40% and 50%, respectively. The results support the development of mezigdomide, currently being evaluated in combination with standard therapies in multiple myeloma as part of a large, ongoing phase I/II trial (NCT03989414) and planned phase III studies (Abstract 568).
Smita Bhatia, MD, MPH, of the Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, discusses study findings that showed key somatic mutations in the peripheral blood stem cell product increases the risk of developing therapy-related myeloid neoplasms (Abstract 119).
Joseph Schroers-Martin, MD, of Stanford University, discusses immunogenomic features reflecting divergent biology in posttransplant lymphoproliferative disorders (PTLD). These include evidence of mismatch repair defects in Epstein-Barr virus–positive PTLD, tumor microenvironment depletion, and MYC pathway enrichment in certain patients (Abstract 72).
Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.