QOL Remains Key Consideration for First-Line Treatment of Anemia in Lower-Risk MDS

Jorge Cortes, MD

Although improving efficacy outcomes remains a key component for the development of therapies and the treatment of anemia in patients with lower-risk myelodysplastic syndrome (MDS), striking a balance between efficacy and quality of life (QOL) is a key consideration when selecting a treatment for this patient population, according to Jorge Cortes, MD.

The first-line treatment paradigm for anemia in this patient population expanded when, in August 2023, the FDA approved luspatercept-aamt (Reblozyl) for the treatment of anemia without prior erythropoiesis-stimulating agent (ESA) use in adult patients with very low– to intermediate-risk MDS who may require regular red blood cell transfusions. Cortes explained that along with the addition of an efficacious treatment option in the first-line setting for this patient population, the frontline approval of luspatercept added another well-tolerated treatment option in this setting.

“We need to think about improving the overall health of the patient [when treating for anemia in lower-risk MDS, including] the QOL of the patient,” Cortes said in an interview with OncLive^®.

In the interview, Cortes discussed the implications of the expanded indication for luspatercept, highlighted the need to consider QOL when selecting a treatment for anemia in patients with lower-risk MDS, and expanded on the ultimate treatment goals for this patient population.

Cortes serves as director and Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer at the Georgia Cancer Center in Augusta.

OncLive: How has the first-line approval of luspatercept affected the treatment paradigm for patients with lower-risk MDS?

Cortes: It's valuable. In patients with low-risk MDS, their main problem is frequently anemia, and with that, all the symptoms [of anemia]. Our [treatment] options that we've had historically have been limited [for anemia in patients with lower-risk MDS]. If patients have 5q deletions, we know that lenalidomide [Revlimid] works well. If patients do not have 5q deletions, some may respond [to lenalidomide], but it's not as good, and [responses] are not as durable.

We also have ESAs, and we use them, but in this context, [patients] have a much better response to luspatercept. That changes the main problem that these patients have. With anemia, patients feel fatigued, they cannot do activities [that come with] daily living, and they can sometimes feel mental fogginess. These are all things that affect the QOL of patients; therefore, it becomes critical to have something that's more effective [in treating anemia for patients with lower-risk MDS without compromising QOL]. The difference [of luspatercept] compared with ESAs was quite significant [in the phase 3 COMMANDS trial (NCT03682536)].

What has been observed regarding QOL for luspatercept vs ESAs in the first-line setting for anemia in patients with lower-risk MDS?

Hemoglobin is not just a number or a value that you're trying to improve. Patients with anemia feel it. They are more tired, and they may be unable to take care of themselves or others. Frequently, [patients with lower-risk MDS] are older, where all these [QOL] issues are amplified, and they may put them at risk of [additional] problems. For example, if a patient is anemic and [already] has a risk of heart attack, [anemia] may increase the risk of developing one of these complications.

[Treating anemia] is not just [seeing] the hemoglobin level rise from 9 g/dL to 10 g/dL. The [QOL] impact is a lot more significant, particularly when talking about a drug that is very well tolerated. Therefore, you are not exchanging one symptom for another [in the form of an adverse effect]; instead, you are providing mostly benefit.

What factors influence risk stratification for treatment in patients with lower-risk MDS?

We always need to look at other factors, such as gene mutations, cytogenetics, and so on. That's part of what goes into classifying a patient as lower-risk. In terms of the anemia itself, you also need to see how symptomatic it is and other elements. All of these factors need to go into the equation when defining that they are low-risk. Not all patients with low-risk MDS are anemic; sometimes they have low-risk [disease] and there's [anemia]; that is not the patient [to consider] for luspatercept.

[We also need] to assess those other elements, such as mutations and cytogenetics, because they also determine the probability that these patients will progress to higher-risk [disease] and require other interventions beyond the management of anemia.

What are the ultimate treatment goals when selecting a therapy for patients with lower-risk MDS?

Patients [with lower-risk MDS] tend to be symptomatic; these are the patients in which you worry about managing anemia. That is what you want to address in these patients. You want to ensure that the patients are tolerating the drug and that they are feeling better and able to do their daily activities. [This is true] whether they are living by themselves and must take care of themselves, or if they are living with others. They may just want to enjoy life, which is [important].

However, we need to be clear that [luspatercept] is not a curative approach; we don't have curative strategies for MDS other than [stem cell] transplant, but [transplant] is not what you're thinking about in a patient with a low-risk MDS. The main goal for these patients is to improve their symptoms and QOL.

Even with luspatercept integrated into the first-line setting for anemia in patients with lower-risk MDS, how could ongoing research address remaining challenges?

The main challenge [is that] the disease will eventually progress and can be fatal. We need to focus on how we can change the natural history of the disease for these patients. Although [stem cell] transplant [is sometimes an option], it is very invasive, and it's not available for many patients with MDS, who tend to be older.

Although we have some good treatments and developments, we're still lacking a transformative approach that could be accessible to most patients that can eradicate the disease and provide a cure, which has been elusive.

Reference

US FDA approves Bristol Myers Squibb's Reblozyl (luspatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes who may require transfusions. News release. Bristol Myers Squibb. August 28, 2023. Accessed October 24, 2024. https://news.bms.com/news/details/2023/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Reblozyl-luspatercept-aamt-as-First-Line-Treatment-of-Anemia-in-Adults-with-Lower-Risk-Myelodysplastic-Syndromes-MDS-Who-May-Require-Transfusions/default.aspx