New Agents for Myelodysplastic Syndromes May Reduce Transfusion Requirements

AT A VIRTUAL symposium held in conjunction with the Asembia Specialty Pharmacy Summit, 2 experts discussed myelodysplastic syndromes (MDS). These conditions can develop de novo (from unknown causes) or pursuant to the use of alkylating agents or topoisomerase inhibitors. Those that emanate from prior use of antineoplastics tend to have a poorer prognosis. Clinicians diagnose between 12,000 and 20,000 new cases of MDS each year. Its chronic prevalence is between 60,000 and 170,000 in the United States.

Clinically, MDS presents with the typical signs and symptoms of blood disorders: anemia, bruising, petechiae, fatigue, and eventually angina and infection. Anthony Perissinotti, PharmD, BCOP, gave participants an overview of these disorders, with an emphasis on lower-risk MDS and the treatment of anemia.

Perissinotti indicated that 90% of patients with myelodysplastic-associated anemia will need transfusions. Transfusions can lead to iron overload, and eventually ineffective erythropoiesis, tissue deposition, and cellular damage. These manifest as cardiac failure, hepatic failure, and endocrine dysfunction, and lead to increased mortality. Currently, the only option for iron overload is to use a chelating agent.

This speaker went on to talk about treatment, focusing on lower-risk MDS. In such cases, treatment depends on whether the anemia is symptomatic and watchful waiting is acceptable in patients who are asymptomatic. Oncologists or hematologists generally treat patients who have symptoms with blood transfusions, erythropoietin-stimulating agents (ESAs), and lenalidomide based on patient- and disease-specific factors. Perissinotti reviewed recent trials using lenalidomide in this diagnosis.

He then went on to talk about a recently approved agent, luspatercept, a recombinant fusion protein with a new mechanism of action, which targets transforming growth factor. This agent has recently been approved for MDS-associated anemia. Evidence for its use in this area is growing. This agent restores erythropoiesis and reduces the need for red blood cell transfusions. Luspatercept is incorporated within the NCCN guidelines for MDS and will likely have increasing use in patients who are refractory to ESAs.

Bhavesh Shah, RPh, BCOP, gave the second half of the presentation, indicating that the economic burden of MDS is considerable. Direct medical resource utilization combined with treatment and supportive care costs can be hefty. Patients who become transfusiondependent tend to have 4 times as many hospitalizations, 3 times as many emergency department visits, 4 times as many inpatient visits, and significantly more office visits than patients who are transfusion independent. The supportive care necessary for this patient population may be extensive.

Specialty pharmacists need to understand that medication costs differ depending on whether the patient is transfusion independent or transfusion dependent, and transfusion-dependent patients have significantly poorer quality of life. Coordination of care for this population is labor intensive as therapies have different distribution strategies, may have REMS requirements, and are administered in various settings, including infusion centers and selfadministered in home settings. Proactive monitoring approaches and adherence assessment may help to improve patient outcomes.

Multidisciplinary approaches to treatment can mitigate the challenges associated with MDS. Eliminating or reducing the need for transfusions using novel agents may fulfill an unmet medical need. Evaluating how agents will be used in treatment algorithms and how their use may shift other resources is necessary to optimize care. Shah concluded by reviewing several agents that are under clinical investigation. These agents may further shift the treatment landscape for patients with MDS-associated anemia.