patient care perspectives

High-Risk MDS and AML: Talking to Patients About Therapeutic Intensity, Risks, and Benefits

by Guillermo Garcia-Manero, MD

Overview

Conversations with patients about initial therapy for high-risk myelodysplastic syndrome (HR-MDS) and acute myeloid leukemia (AML) may include the consideration of the anticipated duration of remissions, tolerability, and quality of life. Clinical trial participation may also be an important part of this discussion.

Expert Commentary

Guillermo Garcia-Manero, MD

Professor and Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research
Chief, Section of Myelodysplastic Syndromes
Department of Leukemia, Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

I am optimistic that, with the novel therapies that are under investigation, more of the medically frail population will have a better chance of achieving remission.”

Guillermo Garcia-Manero, MD

Although treatment approaches for HR-MDS and AML may overlap, the diseases have different US Food and Drug Administration–approved treatment options. In either disease, conversations about initial therapy may involve discussions of therapeutic intensity, side effects, anticipated duration of remissions, and quality-of-life issues. Patients who are younger and medically fit may be more accepting of the side effects associated with aggressive treatment, and they may be candidates for allogeneic hematopoietic stem cell transplantation. In contrast, patients who are older and medically frail might opt for lower-intensity treatment with fewer side effects or perhaps supportive care alone, in some circumstances. Chronological age is just one of the many factors that guide treatment. By taking a holistic approach to each individual, treatment decisions can be tailored to the patient’s medical fitness and comorbidities, as well as their preferences and goals.

Traditionally, the hypomethylating agents (HMAs), including azacitidine and decitabine, have been shown to reduce symptoms, improve quality of life, and prolong survival in a subset of patients with HR-MDS. Thus, HMAs are the backbone of low-intensity treatment; however, they are not the most active of compounds. The combination of an HMA with venetoclax, a BCL-2 inhibitor, or ivosidenib/enasidenib in patients with IDH1/IDH2 mutation has been a positive development in AML and is also promising in HR-MDS; the early data have been very positive, in my opinion.

If the standard of care for HR-MDS were optimal, there might be a reluctance on the part of patients to participate in clinical trials, but what we are seeing is the opposite (ie, patients want to be on these study protocols because the current standard is suboptimal). For such patients, we may administer a low-intensity regimen of decitabine and venetoclax, with the goal of getting more of them to achieve remission, which allows for more patients to proceed to allogeneic stem cell transplantation.

Thus, I think that it is necessary to change the perception of treatment futility and encourage eligible patients to enroll in clinical trials. Such trials might offer patients different, less-intense dosing schedules of established drugs, investigational new therapies and novel targeted combinations, and/or immune-based therapies. Once these investigational trials reach accrual, we will have sufficient data to establish the safety and efficacy of these novel treatments, and we hope for the approval of more treatment options for HR-MDS. Ongoing research will also continue to explore the use of targeted therapy for driver mutations in various settings, including in combination with immune checkpoint inhibitors in AML. It is important that patients have genomic analysis done so as not to miss an opportunity for targeted treatment. I am optimistic that, with the novel therapies that are under investigation, more of the medically frail population will have a better chance of achieving remission.

References

Bewersdorf JP, Carraway H, Prebet T. Emerging treatment options for patients with high-risk myelodysplastic syndrome. Ther Adv Hematol. 2020;11:2040620720955006. doi:10.1177/2040620720955006

Crossnohere NL, Richardson DR, Reinhart C, et al. Side effects from acute myeloid leukemia treatment: results from a national survey. Curr Med Res Opin. 2019;35(11):1965-1970. doi:10.1080/03007995.2019.1631149

DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17. doi:10.1182/blood-2018-08-868752

Estey EH. Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol. 2018;93(10):1267-1291. doi:10.1002/ajh.25214

Garcia-Manero G, Chien KS, Montalban-Bravo G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020;95(11):1399-1420. doi:10.1002/ajh.25950

Kayser S, Levis MJ. Advances in targeted therapy for acute myeloid leukaemia. Br J Haematol. 2018;180(4):484-500. doi:10.1111/bjh.15032

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