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School of Nursing
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
Ashley Leak Bryant, PhD, RN, OCN, FAAN, has disclosed that she has received funds for research support from Jazz.
Myelodysplastic syndromes (MDS) are a spectrum of blood cancers. Many patients with MDS are asymptomatic, but MDS may be suspected if ≥1 cytopenias are detected during routine lab workups. A diagnosis of MDS is made after a bone marrow biopsy. As the disease progresses, bone marrow function declines, resulting in myelosuppression. A subset of patients with MDS will develop symptomatic cytopenias that present primarily with anemia, neutropenia, and thrombocytopenia. Treatment selection for patients with MDS can be complex, and I will discuss risk stratification and treatment of lower-risk MDS while also highlighting the importance of nurses in supportive care.
Risk Stratification in MDS
The Revised International Prognostic Scoring System (IPSS‑R) is an important tool to guide MDS management. This scoring system is used to assess patient risk of progression to acute myeloid leukemia (AML) or death by assigning a score value for different variables including cytogenetics, bone marrow blast percentage, hemoglobin levels, and platelet and neutrophil counts. We consider lower-risk MDS anything with a score <1.5-3.0.
Treatment Selection and Approach for Patients With Lower‑Risk MDS
Several criteria are used to guide treatment selection for patients with lower‑risk MDS. Age and performance status are critically important, as individuals with MDS often are older adults with worse performance status. Comorbid conditions such as chronic kidney disease, high blood pressure, and arthritis may also impact our treatment selection. In addition, the number and depth of cytopenias should be considered. Other important factors are transfusion dependence and frequency, erythropoietin (EPO) level, and karyotype. It is important to measure the patient’s baseline values and monitor for changes over time.
The treatment approach for lower-risk MDS is different depending on whether the patient is experiencing symptoms. For asymptomatic patients, we often observe them until disease progression or symptoms appear, at which point we move forward to treatment. We also can consider molecular testing to supplement risk stratification with IPSS-R to assist in decision-making. The most common symptoms result from anemia, and there are several approaches to anemia management. For patients with anemia and a serum EPO <500 U/L, erythropoiesis-stimulating agents (ESAs) are recommended. Other options for select patient populations include luspatercept, lenalidomide, a hypomethylating agent (HMA), or supportive care alone. For cytopenias other than anemia treatment, options include hematopoietic growth factors, HMAs, immunosuppressive therapy, or supportive care alone. All patients should receive supportive care. Communicating with the patient about clinical trial enrollment is critical in MDS studies, as is breaking down barriers to clinical trial participation by reaching patients who often are underrepresented in MDS trials—older adults with chronic illnesses and Black, indigenous, and people of color.
Luspatercept in Lower-Risk MDS
Luspatercept is one option for anemia management in patients with ring sideroblasts and after ESA failure. MEDALIST was a phase III trial evaluating luspatercept vs placebo in adults with very low-, low-, or intermediate-risk non‒deletion 5q (del[5q]) MDS with ring sideroblasts. Enrolled patients were intolerant to or ineligible for ESAs and were red blood cell (RBC) transfusion dependent. The primary endpoint was RBC-transfusion independence (TI) for ≥8 weeks between Weeks 1 and 24. In the MEDALIST trial, luspatercept significantly reduced transfusion burden and MDS‑related anemia in patients with lower‑risk MDS. The most common any-grade adverse events (AEs) related to luspatercept were fatigue and diarrhea. The most common grade 3/4 AEs with luspatercept were anemia, fatigue, and falls. Four patients progressed to AML during this trial: 3 in the luspatercept arm and 1 in the placebo arm.
Lenalidomide in Lower-Risk MDS
Lenalidomide is approved for patients with low- or intermediate-1–risk MDS, transfusion-dependent anemia, and a del(5q) mutation. Evidence for the efficacy of lenalidomide comes from the MDS‑004 phase III trial comparing lenalidomide vs placebo in transfusion-dependent patients with lower‑risk MDS with del(5q). Lenalidomide increased TI at doses of 5 mg or 10 mg, and the most common grade 3/4 AEs were neutropenia, thrombocytopenia, leukopenia, anemia, and deep vein thrombosis. Although not currently indicated for patients without a del(5q) mutation, the phase III MDS-005 trial found that significantly more patients achieved RBC-TI ≥8 weeks with lenalidomide vs placebo. In the phase III ECOG 2905 study, patients with low or intermediate-1–risk MDS and symptomatic anemia or RBC transfusion dependence received lenalidomide plus EPO alfa or lenalidomide alone. The primary endpoint of major erythroid response was significantly higher with the combination of lenalidomide/EPO alfa.
For MDS, the recommended dosing of lenalidomide is 10 mg/day. At this dose, the most common AEs include myelosuppression with some gastrointestinal concerns, peripheral edema, and coughing. Dose interruptions and dose reductions are used to manage treatment‑related cytopenias. Dose reductions are required for patients with poor kidney function; both creatinine and blood urea nitrogen levels should be monitored closely. There is a boxed warning for hematologic toxicity, thromboembolism, and embryo‑fetal toxicity, so it is important to advise patients of child-bearing age to use contraception to reduce the risk of any embryo‑fetal toxicity.
Hypomethylating Agents and Lower-Risk MDS
Although HMAs such as azacitidine and decitabine are usually used for higher-risk MDS, some evidence supports their use at lower doses for lower-risk MDS. In a phase II trial, low-dose azacitidine or decitabine were evaluated in 113 patients with low- or intermediate-risk MDS or chronic myelomonocytic leukemia. The overall response rate and morphological response were higher with decitabine than with azacitidine.
Oral azacitidine (CC-486), currently approved as maintenance therapy for AML, was evaluated vs placebo in a phase III trial in lower‑risk MDS with transfusion‑dependent anemia and thrombocytopenia. The primary endpoint was RBC-TI ≥56 days. The rate of TI was significantly longer with oral azacitidine, and the median duration of TI was longer. The most common AEs with oral azacitidine were low‑grade GI events, and there were more grade ≥3 AEs than with placebo.
Telomerase Inhibitors in Lower‑Risk MDS
The telomerase inhibitor imetelstat is being investigated for the management of lower-risk MDS. In the phase II IMbark trial, imetelstat was administered to patients with transfusion-dependent lower-risk MDS and resulted in an 8-week RBC-TI rate of 37% in the overall population and 42% in patients with non-del(5q), HMA-naive MDS. The median duration of TI was longer in the non-del(5q), HMA-naive population than the total study population. The phase III IMerge trial is further evaluating imetelstat in transfusion-dependent low- or intermediate–risk MDS after ESA failure.
Nursing Implications for Managing Lower-Risk MDS
Nurses play a vital role in the management cytopenias associated with MDS. One role of the nurse is to help to manage anemia with ESAs and blood transfusions. Nurses also help patients manage their fatigue and may advise them to cluster care and activities that they are doing in their home or in the community. Nurses can also encourage patients to engage in physical activity and walking to manage fatigue and maintain their mobility and function. Patients commonly experience weight loss and decreased appetite, and we encourage them to eat and drink high‑calorie foods throughout the day. Iron chelation therapy is sometimes used to mitigate iron overload for patients with MDS and a high transfusion burden, so patients need to avoid iron supplements or multivitamins with iron.
Nurses also provide support for patients with MDS and their families. Patient education at each encounter is essential to address concerns, clarify medication regimen, and increase how the patient is engaged in their care. One ongoing discussion point is the risk of myelosuppression and how it may impact their social activities and the things they enjoy doing. Patients may become depressed or very anxious, and it is important to discuss this with them and their family. Referrals for psychological or spiritual support may be needed. Referral to a comprehensive cancer support program can help patients manage the feelings of loss of control and limitations on social activities. Thus, nurses play a critical role in the oncology care team for patients with MDS.
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