patient care perspectives
Relapsed AML: Past, Present, and Future
Patients with acute myeloid leukemia (AML) have more options for treatment today than in the past. Our featured expert highlights this progress, noting the potential for more effective, more individualized AML therapy in the future.
Courtney D. DiNardo, MD, MSCE
“In the future, I think that we will be developing even more targeted and individualized options that will be used in rational combinations to treat our patients more effectively.”
In the past, we had our standard intensive chemotherapy that cured only a minority of patients. Many of our older patients who were ineligible for that standard therapy would receive azacitidine or decitabine alone, and treatment was palliative with an anticipated survival of under 1 year, which was certainly discouraging.
In the present paradigm, we have multiple different treatment options for patients, including those who are eligible for intensive chemotherapy and those who are not. For our younger patients or for those who are fit for intensive chemotherapy, we now have the benefit of adding the CD33 monoclonal antibody gemtuzumab ozogamicin for patients with core binding factor AML, or an FLT3 inhibitor for those with FLT3-mutated AML. If they have AML with myelodysplasia-related changes, US Food and Drug Administration–approved CPX-351 is an option, with data showing that it is more efficacious than standard 7+3 therapy (ie, 7 days of cytarabine plus 3 days of daunorubicin).
In our older chemotherapy-ineligible patients, the combination of azacitidine with venetoclax has dramatically improved overall survival. We also have combinations with IDH inhibitors and with FLT3 inhibitors that are under development, so a number of newer treatment options have improved our standard of care, and still others are likely to emerge.
Further, maintenance therapy is another important new paradigm for AML. Oral maintenance therapy (eg, oral azacitidine) is an option for our patients who receive standard intensive chemotherapy and who are not transitioning to allogeneic stem cell transplantation. The goal of this approach is to try to improve the duration of remission and, subsequently, overall survival.
In the future, I think that we will be developing even more targeted and individualized options that will be used in rational combinations to treat our patients more effectively. The “induction, consolidation, and then you're done” paradigm will continue to give way to newer approaches. There will be a continuum or pathway that includes various different combinations, also folding in the targeted therapeutics. Some patients will go to transplant, while others will get more effective maintenance therapies to clear any low-level leukemia that previously persisted at or below the limits of our detection. I think that the maintenance area is where some of our immunotherapy approaches might really be the most effective, where there is less leukemic burden and a better likelihood for that type of immune-modulating approach to be the most effective.
Borthakur G, Kantarjian H. Core binding factor acute myelogenous leukemia-2021 treatment algorithm. Blood Cancer J. 2021;11(6):114. doi:10.1038/s41408-021-00503-6
DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971
Khan N, Hills RK, Virgo P, et al. Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia. Leukemia. 2017;31(5):1059-1068. doi:10.1038/leu.2016.309
Lambert J, Pautas C, Terré C, et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019;104(1):113-119. doi:10.3324/haematol.2018.188888
Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26):2684-2692. doi:10.1200/JCO.2017.77.6112
Molica M, Breccia M, Foa R, Jabbour E, Kadia TM. Maintenance therapy in AML: the past, the present and the future. Am J Hematol. 2019;94(11):1254-1265. doi:10.1002/ajh.25620
Rautenberg C, Stölzel F, Röllig C, et al. Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia. Blood Cancer J. 2021;11(10):164. doi:10.1038/s41408-021-00558-5