Key Takeaways
Challenging Cases in Cancer
Managing Lower Risk Myelodysplastic Syndromes

MDS Incidence

• 1 in 3 patients will progress to AML
• 58% of patients are defined as low-risk MDS
• Anemia is the most common clinical feature
• More than 90% of patients harbor somatic mutations
  

MDS Classification

• The Harmonized WHO/ICC 2022 Classification System
  • Cytogenic abnormalities- TP53m, SF3B1, del5q
  • Morphological criteria- defined by blasts
• IPSS-M Classification System- Prognostic Scoring System
  • Bone marrow blasts
  • Cytogenetics
  • Cytopenia’s

Case Presentations and Management

1. 75-year-old gentleman with a longstanding history of anemia was under observation by his local oncologist.

Initial Workup

• CBC: Hgb of 8 g/dL, ANC of 3000 K/uL, and platelets of 400 K/uL
• Epo level: 125 U/L

Bone marrow biopsy

• 50% cellularity
• 26% ring sideroblasts
• No increase in blasts
• Megaloblastic changes in the erythroid lineages
• Cytogenetics: Trisomy 8 in 10/20 metaphases
• NGS panel results: SF3B1 mutation: VAF 40%
  

Initial Management

• Patient became red blood cell transfusion-dependent (RBC-TD), receiving two units every 2 weeks.
• Placed on Imetelstat at 7.1 mg/kg every 4 weeks after 1L failure with erythropoietin
• There were two occurrences of grade 3 thrombocytopenia, Imetelstat held until platelet recovery, and then the dose was reduced to 5.6 mg/kg for cycle five.

1. 68-year-old female with a history of hypothyroidism presented to the ER with shortness of breath.

Initial Workup

• CBC: Hgb 7.0 g/dL, ANC of 2000 K/uL, and platelets of 270 K/uL
• Epo level: 225 U/L

Bone marrow biopsy

• Hypercellular
• Erythroid dysplasia
• 30% ring sideroblasts
• No increase in blasts
• Cytogenetics: Normal karyotype
• NGS panel results: SF3B1 mutation: VAF 30%, TET-2 mutation: VAF 40%

Initial Management

• Patient started on Luspatercept dosed at 1 mg/kg every 3 weeks and escalated to 1.75 mg/kg based on the MEDALIST data.
• The patient then achieved a good response, remaining RBC-TI for 6 months.
• Repeat bone marrow biopsy performed and revealed consistent findings: MDS-RS, SF3B1, SRSF2, TET-2
• The patient started on Imetelstat 7.1 mg/kg every 4 weeks. After cycle 2, the patient became RBC-TI.
• The patient continues tolerating treatment well, not requiring dose reductions. The last Hgb was 10.6 g/dL.

Collaborative Approach and Conclusion

• Referral to MDS Centers of Excellence: Patients can be referred to specialized centers at the time of diagnosis for comprehensive evaluation and treatment recommendations.
• Collaboration: Treatment recommendations and opportunities for research identified and communicated to the local community oncology centers.
• Telemedicine: Incorporating telemedicine follow-up visits between community center visits can provide additional support for patients and providers until patient responses are achieved.