Myelodysplastic syndromes (MDS) are a spectrum of clonal hematologic stem cell malignancies. This form of cancer is characterized by dysplastic and ineffective hematopoiesis, peripheral cytopenias, recurrent cytogenetic or molecular abnormalities, and variable risk for leukemic transformation.
During the 2022 Oncology Nurse Advisor Summit, a session led by Sandra Kurtin, PhD, ANP-C, AOCN, of the University of Arizona Cancer Center in Tucson, outlined the pathophysiology, risks, prognosis, and challenges in patients with MDS; therapeutic options (current and emerging) for MDS; and the multidisciplinary management strategies for common adverse events in MDS.1
Long-term historic data related to the incidence and prevalence of MDS is unavailable due to the fact that MDS were not incorporated into the Surveillance, Epidemiology, and End Results (SEER) Program until 2001-2003. It is estimated that there are 60,000 existing cases of MDS, but Dr Kurtin explained that the number is likely higher. The low estimate may be related to the fact that this disease occurs mostly in older adults (median age at onset is 76 years) and recent advances in disease recognition and diagnostic capabilities coupled with evolving treatment options now allow for a more complete view of this patient population. In addition, the number of secondary or treatment-related MDS cases in patients who have received chemotherapy or radiotherapy for other types of cancers is also contributing to the growing number of cases.
In diagnosing MDS, Dr Kurtin stressed the importance of evaluating patient history, including comorbidities, performance status, and cytopenias, which determine whether a patient can endure more aggressive treatment. Most patients present with 1 or more cytopenias and it’s important that blood work be conducted to rule out other causes. Ultimately a tissue biopsy is required for diagnosis of MDS.
Dr Kurtin also reviewed the World Health Organization Classification of Tumors and Haematopoietic and Lymphoid Tissues, which were updated in 2016.2 These guidelines are highly specific and include MDS with single lineage dysplasia, MDS with ring sideroblasts, MDS with multilineage dysplasia, MDS with excess blasts, MDS with isolated del(5q), and myelodysplastic/myeloproliferative neoplasms.
After diagnosis, clinicians will look for certain factors to risk stratify a patient’s disease.
The Revised International Prognostic Scoring System (IPSS-R) was developed by an international group of experts who evaluated more than 13,000 patients with MDS.3 This scoring system evaluates cytogenetics, the number of blasts, the number of cytopenias, and the depth of the cytopenias. Patients with very low-risk disease have a life expectancy of 8.7 years without treatment, while patients with very high-risk disease have a life expectancy of less than a year without treatment (which is largely attributed to leukemic transformation).
Mutational status is another factor to consider in the diagnosis and treatment planning for patients with MDS. A sole SF3B1 mutation is associated with a more favorable prognosis. There also are a number of mutations (TET2, DNMT3A, GPR98, ZRSR2, BCOR, APC, SUZ12, PRP58, CUV1, DDX54, IDH1, KDM6A, PHF6, SETBP1) that have an intermediate or undefined impact on overall survival. Notably, Dr Kurtin explained, ASXL1, STAG2, RUNX1, U2Af1, TP53, NF1, EXH2, CBL, and NRAS are known to be associated with inferior overall survival in patients with MDS.
Outside of the disease characteristics, Dr Kurtin explained, look at the patient as a whole, particularly for the presence or absence of comorbidities and whether or not they are frail, as this is strongly related to prognosis and a patient’s ability to tolerate therapy.
When selecting therapy, consider if disease-modifying therapy is required or if supportive care would be preferred. Transfusion dependence, progression of symptomatic cytopenias, increasing blasts, and high-risk disease are all considered triggers for the initiation of disease-modifying treatment. Dr Kurtin described the importance for risk-adapted treatment selection that accounts for a patient’s risk category, comorbidities, performance status, lifestyle, quality of life, and financial considerations. Allogeneic stem cell transplants (alloHCT) are the only potentially curative therapy for MDS. However, many patients with MDS do not meet eligibility criteria for alloHCT. If alloHCT is not feasible, treatment should continue until disease progression or unacceptable toxicity.
In patients with lower-risk MDS the goals of treatment typically include achieving transfusion independence, decreasing symptom burden of iron overload, and improving quality of life, Dr Kurtin explained. Supportive care strategies, which do not change the underlying disease, include transfusion, erythropoietin stimulating agents, chelation agents, antibiotics, optimizing treatment for comorbidities, and palliative care. Disease-modifying therapies for MDS include differentiating agents, immunodulatory agents (lenalidomide), hypomethylating agents (azacitidine and decitabine), and clinical therapies and evolving therapies.
There are many future targets for patients with MDS, which highlights the continued need to enroll patients in clinical trials in order to see more therapeutic options for patients.
Common adverse events in patients who receive disease-modifying agents are anemia, neutropenia, thrombocytopenia, nausea and vomiting, constipation, and fatigue. Patients may also experience adverse events related to the specific drug they receive, which can include injection-site reactions for subcutaneous administration (azacitidine); rash, pruritus, REMS for potential teratogenicity, renal and hepatic toxicities (lenalidomide); and syncope and dyspnea (luspatercept).
Multidisciplinary management of the patient with low-risk MDS is essential for early identification and prompt mitigation of adverse events. Dr Kurtin explained that consistent communication across team members fosters trust and engagement of the patient and supportive care is essential for all patients with MDS to improve quality of life.
“The entire team is involved in supporting the patient and improving their quality of life and our goal is really to minimize adverse events so that patients can stay on their therapy,” Dr Kurtin concluded. “Quality of life really needs to be our driving force along with optimal disease control to prolong life.”
- Kurtin S. Optimizing outcomes in low-risk myelodysplastic syndromes. Oral presentation at: 2022 Oncology Nurse Advisor Summit; March 25-27, 2022.
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. doi:10.1182/blood-2016-03-643544. Erratum in: Blood. 2016;128(3):462-463. doi:10.1182/blood-2016-06-721662
- Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. doi:10.1182/blood-2012-03-420489
This article originally appeared on Oncology Nurse Advisor