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BCOP - Adult Acute Leukemias and Myelodysplastic Syndromes > Myelodysplastic Syndromes > Flashcards

Myelodysplastic Syndromes Flashcards

1
Q

*

Myelodysplastic Syndromes

Chromosomal Abnormalities

A

Chromosome 5 - Most common Chromosomal abnormalitiy in MDS

Other Chromosomal abnormalities - Chromosomes 3, 5, 7, 8, 11, 17, 20

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2
Q

Myelodysplastic Syndromes

Gene Mutations associated with Adverse Clinical Features

A
  • Complex Karyotype (TP53)
  • Excess Bone Marrow Blast Proportion (RUNX1, NRAS, and TP53)
  • Severe Thrombocytopenia (RUNX1, NRAS and TP53)
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3
Q

Myelodysplastic Syndromes

Risk Factors

A

Previous Exposure:
- Alkylating Agents
- Topoisomerase II Inhibitors
- Ionizing Radiation

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4
Q

Myelodysplastic Syndromes

Mutations and Prognostic Factors

A

SF3B1 mutation has been associated with a more favorable prognosis

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5
Q

Myelodysplastic Syndromes

Treatment

Goals of Therapy

A
  • Alteration of the natural history of the disease / delaying disease progression
  • Reducing number of red blood cell transfusions
  • Improving quality of life
  • Prolonging survival
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6
Q

Myelodysplastic Syndromes

Treatment

Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

A

Only Curative therapy

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7
Q

Myelodysplastic Syndromes

Treatment

Recommended Therapies

Lower-Risk Disease

A

Patients with lower-risk disease may benefit from:
- ** hematopoietic growth factors** (ie: erythropoietin stimulating agents [ESA] and luspatercept)
- hypomethylating agents
- Immunosuppressive therapy
- immunomodulating agents (ie: lenalidomide).

Therapy in this subset of patients is based on transfusion needs. Patients that are transfusion independent are typically observed until they become transfusion dependent.

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8
Q

Myelodysplastic Syndromes

Treatment

Recommended Therapies

Higher-Risk Disease

A

High-Risk = More likely to progress to AML

May Benefit from:
- Hypomethylating agents
- Intensive Chemotherapy
- Allogeneic HCT

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9
Q

Myelodysplastic Syndromes

Treatment- LOWER-RISK MDS

Recommended Therapies

Hematopoietic Growth Factors

A

Neither granulocyte/macrophage colony stimulating factor (GCSF/GMCSF), thrombopoietin receptor agonists, luspatercept, nor ESA change the natural history of the disease.

GCSF increases circulating neutrophils and may decrease the risk of infections.
- GCSF not recommended for routine prophylaxis. Consider if recurrent.

ESA increase hematocrit in 30-58% of MDS patients
- Titrate to acheive goal Hgb 10-12 g/dL
- Best response when pts baseline EPO is <500U/L

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10
Q

Myelodysplastic Syndromes

Treatment - LOWER-RISK MDS

Recommended Therapies

Lenalidomide

A

An immunomodulating agent with demonstrated activity in lower-risk MDS

Particularly beneficial in patients w/ del(5q) as sole chromosomal abnormality

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11
Q

Myelodysplastic Syndromes

Treatment - LOWER-RISK MDS

Recommended Therapies

Luspatercept

A

First in class recombinant fusion protein that inhibits the transforming growth
factor dependent stages of erythroid maturation

COMMANDS Trial
- Incidence of RBC transfusion independence favored Luspatercept vs Epoetin alfa
- Patients without ringed sideroblasts did not benefit from luspatercept over epoetin alfa

FDA APPROVAL INDICATIONS:
- EPO-naive setting = luspattercept approve regardless of ringed sideroblasts
- EPO-refractory/intolerant = ringed sideroblasts MUST be present

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12
Q

Myelodysplastic Syndromes

Treatment - LOWER-RISK MDS

Recommended Therapies

Luspatercept

Adverse Events

A

Adverse Reactions
- Thrombocytopenia
- Fatigue
- Peripheral Edema
- Nausea
- Dyspnea
- Hypertension

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13
Q

Myelodysplastic Syndromes

Treatment - LOWER-RISK MDS

Recommended Therapies

Immunosuppressive Therapies

Agents

A

Can be used to treat the cytopenias associated with MDS
- Equine anti-thymocyte globulin (ATG)
- steroids
- cyclosporine
- eltrombopag

Approximately 30% of MDS patients respond to these agents

Sustained increases in:
- Hemoglobin
- Neutrophils
- Platelet Production

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14
Q

Myelodysplastic Syndromes

Treatment - LOWER-RISK MDS

Recommended Therapies

Immunosuppressive Therapies

Predictive Response Characteristics

A
  • Younger age (≤60 years old)
  • Shorter duration of red cell transfusion dependence (RCTD)
  • Overrepresentation of the class II histocompatibility antigen DR15 (HLA-DR15)
  • Bone marrow hypoplasia (<5% blasts)
  • Normal cytogenetics
  • Evidence of a paroxysmal nocturnal hemoglobinuria (PNH) clone
  • STAT-3 mutant cytotoxic T-cell clones
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15
Q

Myelodysplastic Syndromes

Treatment - LOWER-RISK MDS

Recommended Therapies

Hypomethylating Agents

A

Azacitadine and Decitabine

Lower-Risk MDS:
- Some studies have demonstrated clinical benefit w/ low doses of azacitadine/decitabine

Appropriate option for lower-risk patients w/ symptomatic anemia and elevated epoetin levels who are NOT expected to respond to other treatment options

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16
Q

Myelodysplastic Syndromes

Treatment - HIGHER-RISK DISEASE

Recommended Therapies

A
  • Hypomethylating Agents
  • Intensive Chemotherapy (Anthracyclines, Cytarabine, Fludarabine)
  • Ivosidenib
17
Q

Myelodysplastic Syndromes

Treatment - HIGHER-RISK DISEASE

Recommended Therapies

Hypomethylating Agents

A

Considered standard of care in this subgroup

  • Azacitadine/Decitabine = theoretically similar
    • Azacitadine preferred by NCCN (proven survival benefit)
  • 4-6 cycles of treatment required to determine treatment failure
18
Q

Myelodysplastic Syndromes

Treatment - HIGHER-RISK DISEASE

Recommended Therapies

Hypomethylating Agents

A

Regimens used for induction therapy in AML may be considered in patients w/ good performance status and few co-morbidities who are awaiting allogeneic HCT

Most important factor of response to AML-like therapy is karyotype
- unfavorable karyotype (complex karyotpe or del(7q)) have low response rate/short duration of response

19
Q

Myelodysplastic Syndromes

Treatment - HIGHER-RISK DISEASE

Recommended Therapies

Ivosidenib

A

FDA Approved for R/R MDS based on 19 patients with R/R MDS

  • Small number study and difficult to understand safety or efficacy in this population
20
Q

Myelodysplastic Syndromes

Sumary of Preferred Treatment Options

HIGHER RISK

A

Image PAGE 10

21
Q

Myelodysplastic Syndromes

Sumary of Preferred Treatment Options

LOWER RISK

A

Image PAGE 10

22
Q

Myelodysplastic Syndromes

Iron Chelation Therapy

SUMMARY

A
  • Therapy for MDS may alleviate patient RBC need but substatial proportion of patients may not respond to tx and develop IRON OVERLOAD
  • -> Increased risk of Hepatic, Cardiac and Endocrine Damage
  • NO studies demonstrating Overall Survival Benefit w/ iron chelation in MDS
23
Q

Myelodysplastic Syndromes

Iron Chelation Therapy

Treatment

A
  • If > 20 RBC transfusions have been received
    AND
  • Serum Ferritin >2500 ng/mL:

–> Consider daily iron chelation to decrease iron overload
- Deferoxamine or Deferasirox

Deferoxamine AVOID if CrCl <40ml/min

Deferasirox contraindicated in patients with high-risk MDS due to possibility of liver or kidney impairment and GI bleeding

BCOP - Adult Acute Leukemias and Myelodysplastic Syndromes (2 decks)

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