Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

lower-risk disease: asymptomatic

1st line – observation

Back
ACUTE
|
lower-risk disease: asymptomatic
1st line – 

observation

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Patients with lower-risk disease who are asymptomatic can be monitored without treatment until symptoms, complications with cytopenias, or disease progression occur, or are likely to occur.[16]

lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia

1st line – lenalidomide or erythropoiesis-stimulating agent (ESA)

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
1st line – 

lenalidomide or erythropoiesis-stimulating agent (ESA)

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Lenalidomide (preferred) or an ESA (e.g., epoetin alfa, darbepoetin alfa) is recommended for initial treatment of symptomatic anemia in lower-risk patients with MDS-5q (i.e., MDS with del(5q), with or without one other cytogenetic abnormality except those involving chromosome 7) and erythropoietin levels ≤500 IU/L.[15]

Patients who fail to respond (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) to an ESA prescribed first-line can be considered for lenalidomide therapy, if absolute neutrophil count is >500/microliter and platelet count is >50,000/microliter.[15]

See local specialist protocol for dosing guidelines.

Primary options

lenalidomide

OR

epoetin alfa

OR

darbepoetin alfa

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – clinical trial or hypomethylating agent

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
2nd line – 

clinical trial or hypomethylating agent

A clinical trial or treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine) is recommended if there is no response to initial treatment with lenalidomide or an ESA (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) in patients with MDS-5q who have symptomatic anemia and erythropoietin levels ≤500 IU/L.[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

OR

decitabine

OR

decitabine/cedazuridine

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

3rd line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
3rd line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with MDS-5q and symptomatic anemia and erythropoietin levels ≤500 IU/L who do not respond to (or are intolerant of) treatment with hypomethylating agents can be treated with ivosidenib if they have IDH1 mutations.[15]

Patients who do not have IDH1 mutations should be considered for a clinical trial (if available and eligible) or allogeneic SCT (for select patients).[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71]​ Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.[15]

1st line – lenalidomide

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
1st line – 

lenalidomide

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Lenalidomide is recommended for initial treatment of symptomatic anemia in lower-risk patients with MDS-5q (i.e., MDS with del(5q), with or without one other cytogenetic abnormality except those involving chromosome 7) and erythropoietin levels >500 IU/L.[15]

See local specialist protocol for dosing guidelines.

Primary options

lenalidomide

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – clinical trial or hypomethylating agent

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
2nd line – 

clinical trial or hypomethylating agent

A clinical trial or treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine) is recommended if there is no response to initial treatment with lenalidomide (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) in patients with MDS-5q who have symptomatic anemia and erythropoietin levels >500 IU/L.[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

OR

decitabine

OR

decitabine/cedazuridine

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy (consult local hospital guidelines).[15]

3rd line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
3rd line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with MDS-5q and symptomatic anemia and erythropoietin levels >500 IU/L who do not respond to (or are intolerant of) treatment with hypomethylating agents can be treated with ivosidenib if they have IDH1 mutations.[15]

Patients who do not have IDH1 mutations should be considered for a clinical trial (if available and eligible) or allogeneic SCT (for select patients).[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-5q (del(5q) ± one other cytogenetic abnormality except those involving chromosome 7) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia

1st line – luspatercept

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
1st line – 

luspatercept

​Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Luspatercept is recommended for initial treatment of symptomatic anemia in lower-risk patients with MDS-SF3B1 (i.e., MDS with no del(5q) with or without other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) and erythropoietin levels ≤500 IU/L.[15][73]

See local specialist protocol for dosing guidelines.

Primary options

luspatercept

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – imetelstat; or erythropoiesis-stimulating agent (ESA) ± granulocyte colony-stimulating factor (G-CSF)

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
2nd line – 

imetelstat; or erythropoiesis-stimulating agent (ESA) ± granulocyte colony-stimulating factor (G-CSF)

Imetelstat or an ESA (e.g., epoetin alfa, darbepoetin alfa) is recommended if there is no response to initial treatment with luspatercept (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) in patients with MDS-SF3B1 who have symptomatic anemia and erythropoietin levels ≤500 IU/L.[15]

G-CSF (e.g., filgrastim) may be combined with an ESA to treat anemia. Evidence suggests that G-CSF may improve the erythroid response rate of ESAs.[74]​ A validated decision model has been developed for predicting erythroid responses to ESAs plus G-CSF based on erythropoietin level and number of previous red blood cell (RBC) transfusions.[75]

See local specialist protocol for dosing guidelines.

Primary options

imetelstat

OR

epoetin alfa

OR

darbepoetin alfa

OR

epoetin alfa

and

filgrastim (G-CSF)

OR

darbepoetin alfa

and

filgrastim (G-CSF)

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15] 

3rd line – clinical trial or hypomethylating agent

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
3rd line – 

clinical trial or hypomethylating agent

Patients with MDS-SF3B1 and symptomatic anemia and erythropoietin levels ≤500 IU/L who do not respond to treatment with imetelstat or ESAs (with or without G-CSF) can be considered for a clinical trial (if available and eligible) or treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine).[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

Secondary options

decitabine

OR

decitabine/cedazuridine

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

4th line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
4th line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with MDS-SF3B1 and symptomatic anemia and erythropoietin levels ≤500 IU/L who do not respond to (or are intolerant of) third-line treatment with hypomethylating agents can be treated with ivosidenib if they have IDH1 mutations, or considered for a clinical trial or allogeneic SCT if they do not have IDH1 mutations.[15]

Patients who do not respond to ivosidenib can be considered for a clinical trial or allogeneic SCT.[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

1st line – luspatercept or imetelstat

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
1st line – 

luspatercept or imetelstat

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Luspatercept or imetelstat is recommended for initial treatment of symptomatic anemia in lower-risk patients with MDS-SF3B1 (i.e., MDS with no del(5q) with or without other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) and erythropoietin levels >500 IU/L.[15][73]

See local specialist protocol for dosing guidelines.

Primary options

luspatercept

OR

imetelstat

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – lenalidomide

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
2nd line – 

lenalidomide

Lenalidomide can be considered if there is no response to initial treatment with luspatercept or imetelstat (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) in patients with MDS-SF3B1 who have symptomatic anemia and erythropoietin levels >500 IU/L.[15]

See local specialist protocol for dosing guidelines.

Primary options

lenalidomide

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

3rd line – clinical trial or hypomethylating agent

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
3rd line – 

clinical trial or hypomethylating agent

Patients with MDS-SF3B1 and symptomatic anemia and erythropoietin levels >500 IU/L who do not respond to treatment with lenalidomide should be considered for a clinical trial (if available and eligible) or treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine).[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

Secondary options

decitabine

OR

decitabine/cedazuridine

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

​Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

4th line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
4th line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with MDS-SF3B1 and symptomatic anemia and erythropoietin levels >500 IU/L who do not respond to (or are intolerant of) third-line treatment with hypomethylating agents can be treated with ivosidenib if they have IDH1 mutations, or considered for a clinical trial or allogeneic SCT if they do not have IDH1 mutations.[15]

Patients who do not respond to ivosidenib can be considered for a clinical trial or allogeneic SCT.[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[70]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: MDS-SF3B1 (no del(5q) ± other cytogenetic abnormalities with ring sideroblasts ≥15% [or ≥5% with an SF3B1 mutation]) with symptomatic anemia
|
with erythropoietin levels >500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic stem cell transplantation.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic stem cell transplantation should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia

1st line – erythropoiesis-stimulating agent (ESA) alone or luspatercept

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
1st line – 

erythropoiesis-stimulating agent (ESA) alone or luspatercept

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

An ESA alone (e.g., epoetin alfa, darbepoetin alfa) or luspatercept is recommended for initial treatment of symptomatic anemia in lower-risk patients with no del(5q) with or without other cytogenetic abnormalities and ring sideroblasts <15% (or <5% with an SF3B1 mutation) and erythropoietin levels ≤500 IU/L.[15][76]

Patients who fail to respond (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) to an ESA prescribed first-line can be considered for luspatercept therapy.[15]

See local specialist protocol for dosing guidelines.

Primary options

epoetin alfa

OR

darbepoetin alfa

OR

luspatercept

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – erythropoiesis-stimulating agent (ESA) ± granulocyte colony-stimulating factor (G-CSF) or lenalidomide; or imetelstat; or lenalidomide alone

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
2nd line – 

erythropoiesis-stimulating agent (ESA) ± granulocyte colony-stimulating factor (G-CSF) or lenalidomide; or imetelstat; or lenalidomide alone

​G-CSF (e.g., filgrastim) or lenalidomide may be combined with an ESA if there is no response to initial treatment with an ESA alone or luspatercept (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) in patients with no del(5q) and ring sideroblasts <15% (or <5% with an SF3B1 mutation) who have symptomatic anemia and erythropoietin levels ≤500 IU/L.[15]

Imetelstat or lenalidomide alone can also be considered if there is no response to initial treatment in these patients.

Evidence suggests that G-CSF may improve the erythroid response rate of ESAs.[74]​ A validated decision model has been developed for predicting erythroid responses to ESAs plus G-CSF based on erythropoietin level and number of previous red blood cell transfusions.[75]

See local specialist protocol for dosing guidelines.

Primary options

epoetin alfa

OR

darbepoetin alfa

OR

epoetin alfa

and

filgrastim (G-CSF)

OR

epoetin alfa

and

lenalidomide

OR

darbepoetin alfa

and

filgrastim (G-CSF)

OR

darbepoetin alfa

and

lenalidomide

OR

imetelstat

OR

lenalidomide

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

3rd line – clinical trial or hypomethylating agent

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
3rd line – 

clinical trial or hypomethylating agent

Patients with no del(5q) and ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia and erythropoietin levels ≤500 IU/L who do not respond to treatment with an ESA (with or without G-CSF or lenalidomide) or imetelstat can be considered for a clinical trial (if available and eligible) or treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine).[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

Secondary options

decitabine

OR

decitabine/cedazuridine

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

4th line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
4th line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with no del(5q) and ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia and erythropoietin levels ≤500 IU/L who do not respond to (or are intolerant of) third-line treatment with hypomethylating agents can be treated with ivosidenib if they have IDH1 mutations, or considered for a clinical trial or allogeneic SCT if they do not have IDH1 mutations.[15]

Patients who do not respond to ivosidenib can be considered for a clinical trial or allogeneic SCT.[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels ≤500 IU/L
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

1st line – antithymocyte globulin (ATG) ± cyclosporine ± eltrombopag

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and likely to respond to immunosuppressive therapy
1st line – 

antithymocyte globulin (ATG) ± cyclosporine ± eltrombopag

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Lower-risk patients with no del(5q) with or without other cytogenetic abnormalities and ring sideroblasts <15% (or <5% with an SF3B1 mutation) who have symptomatic anemia and erythropoietin levels >500 IU/L should be evaluated for suitability for immunosuppressive therapy (IST).

Patients who are likely to respond to IST (e.g., those with hypocellular bone marrow) can be treated with IST comprising antithymocyte globulin (ATG) with or without cyclosporine.[15][77]​ Eltrombopag may be combined with IST. A corticosteroid (e.g., prednisone) should be given alongside ATG to prevent serum sickness.

IST may be effective in patients ages ≤60 years with ≤5% marrow blasts, or in those who have the following features: HLA-DR15 positivity; paroxysmal nocturnal hemoglobinuria (PNH) clone; or STAT-3 mutant T-cell clone. However, the evidence is mixed.[77][78][79][80][81]

See local specialist protocol for dosing guidelines.

Primary options

lymphocyte immune globulin, anti-thymocyte globulin (equine)

and

prednisone

OR

lymphocyte immune globulin, anti-thymocyte globulin (equine)

and

prednisone

and

cyclosporine modified

OR

lymphocyte immune globulin, anti-thymocyte globulin (equine)

and

prednisone

and

eltrombopag

OR

lymphocyte immune globulin, anti-thymocyte globulin (equine)

and

prednisone

and

cyclosporine modified

and

eltrombopag

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and likely to respond to immunosuppressive therapy
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15]​ Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – clinical trial or hypomethylating agent or imetelstat or lenalidomide

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and likely to respond to immunosuppressive therapy
2nd line – 

clinical trial or hypomethylating agent or imetelstat or lenalidomide

A clinical trial (if available) or treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine) or imetelstat is recommended if there is no response to initial treatment with IST (i.e., no improvement in hemoglobin or no reduction in red blood cell transfusion requirement) in patients with no del(5q) and ring sideroblasts <15% (or <5% with an SF3B1 mutation) who have symptomatic anemia and erythropoietin levels >500 IU/L.[15]

Lenalidomide may also be considered if absolute neutrophil count is >500/microliter and platelet count is >50,000/microliter.[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

OR

imetelstat

Secondary options

decitabine

OR

decitabine/cedazuridine

Tertiary options

lenalidomide

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and likely to respond to immunosuppressive therapy
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15]​ Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

3rd line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and likely to respond to immunosuppressive therapy
3rd line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with no del(5q) and ring sideroblasts <15% (or <5% with an SF3B1 mutation) and symptomatic anemia and erythropoietin levels >500 IU/L who do not respond to (or are intolerant of) treatment with hypomethylating agents, imetelstat, or lenalidomide can be treated with ivosidenib if they have IDH1 mutations.[15]

Patients who do not have IDH1 mutations should be considered for a clinical trial (if available and eligible) or allogeneic SCT (for select patients).[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and likely to respond to immunosuppressive therapy
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

1st line – clinical trial or hypomethylating agent or imetelstat or lenalidomide

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and unlikely to respond to immunosuppressive therapy
1st line – 

clinical trial or hypomethylating agent or imetelstat or lenalidomide

Treatment is based on risk assessment (e.g., using the Revised International Prognostic Scoring System [IPSS-R]), disease type/characteristics (e.g., cytogenetic abnormalities, ring sideroblasts), symptoms, and erythropoietin levels (in patients with anemia).[12][15]

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to IPSS-R) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

Lower-risk patients with no del(5q) with or without other cytogenetic abnormalities and ring sideroblasts <15% (or <5% with an SF3B1 mutation) who have symptomatic anemia and erythropoietin levels >500 IU/L should be evaluated for suitability for immunosuppressive therapy (IST).

Patient who are unlikely to respond to IST (e.g., those without hypocellular bone marrow) can be considered for a clinical trial (if available and eligible) or initial treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine) or imetelstat.[15][77]

Lenalidomide may also be considered if absolute neutrophil count is >500/microliter and platelet count is >50,000/microliter.[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

OR

imetelstat

Secondary options

decitabine

OR

decitabine/cedazuridine

Tertiary options

lenalidomide

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and unlikely to respond to immunosuppressive therapy
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and unlikely to respond to immunosuppressive therapy
2nd line – 

ivosidenib or clinical trial or allogeneic stem cell transplantation (SCT)

Patients with no del(5q) and ring sideroblasts <15% (or <5% with an SF3B1 mutation) and symptomatic anemia and erythropoietin levels >500 IU/L who do not respond to (or are intolerant of) initial treatment with hypomethylating agents, imetelstat, or lenalidomide can be treated with ivosidenib if they have IDH1 mutations.

Patients who do not have IDH1 mutations should be considered for a clinical trial (if available and eligible) or allogeneic SCT (for select patients).[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
lower-risk disease: no del(5q) with ring sideroblasts <15% (or <5% with an SF3B1 mutation) with symptomatic anemia
|
with erythropoietin levels >500 IU/L and unlikely to respond to immunosuppressive therapy
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

lower-risk disease: with clinically relevant thrombocytopenia or neutropenia (without symptomatic anemia)

1st line – clinical trial; or hypomethylating agent; or antithymocyte globulin (ATG) + cyclosporine ± eltrombopag; or eltrombopag alone

Back
ACUTE
|
lower-risk disease: with clinically relevant thrombocytopenia or neutropenia (without symptomatic anemia)
1st line – 

clinical trial; or hypomethylating agent; or antithymocyte globulin (ATG) + cyclosporine ± eltrombopag; or eltrombopag alone

Patients with lower-risk disease (e.g., very-low, low, or intermediate risk according to the Revised International Prognostic Scoring System [IPSS-R]) have a relatively low risk of progression to acute myeloid leukemia (AML) and death.

Treatment for lower-risk disease is focused on improving quality of life by reducing symptoms, reducing transfusion need, and preventing complications associated with cytopenias.

A clinical trial or a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine) is recommended for initial treatment of patients with lower-risk disease who have clinically relevant thrombocytopenia or neutropenia (without symptomatic anemia).[15]

Patients likely to respond to immunosuppressive therapy (IST; e.g., those with hypocellular bone marrow) can be considered for initial treatment with ATG plus cyclosporine (with or without eltrombopag).[15][77]

IST may be effective in patients ages ≤60 years with ≤5% marrow blasts, or in those who have the following features: HLA-DR15 positivity; paroxysmal nocturnal hemoglobinuria (PNH) clone; or STAT-3 mutant T-cell clone. However, the evidence is mixed.[77][78][79][80][81]​​​

Eltrombopag alone can be considered for treatment of severe or life-threatening thrombocytopenia in lower-risk patients.[15]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

OR

decitabine

OR

decitabine/cedazuridine

OR

lymphocyte immune globulin, anti-thymocyte globulin (equine)

and

prednisone

and

cyclosporine modified

OR

lymphocyte immune globulin, anti-thymocyte globulin (equine)

and

prednisone

and

cyclosporine modified

and

eltrombopag

OR

eltrombopag

Plus – supportive care

Back
ACUTE
|
lower-risk disease: with clinically relevant thrombocytopenia or neutropenia (without symptomatic anemia)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Platelet transfusions are recommended for thrombocytopenic bleeding.[15] Platelet transfusions should not be used routinely in patients with thrombocytopenia in the absence of bleeding unless platelet count is <10,000/microliter.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – hypomethylating agent or ivosidenib or romiplostim or clinical trial or allogeneic stem cell transplantation (SCT)

Back
ACUTE
|
lower-risk disease: with clinically relevant thrombocytopenia or neutropenia (without symptomatic anemia)
2nd line – 

hypomethylating agent or ivosidenib or romiplostim or clinical trial or allogeneic stem cell transplantation (SCT)

A hypomethylating agent (if not previously used) or ivosidenib (if patients have IDH1 mutations) can be considered if there is disease progression or no response to initial treatment of clinically relevant thrombocytopenia or neutropenia in lower-risk patients.[15]

Romiplostim can be considered for treatment of severe or refractory thrombocytopenia.[15][82]

Patients who do not have IDH1 mutations should be considered for a clinical trial (if available and eligible) or allogeneic SCT (for select patients).[15]

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

Patients should be assessed for suitability for allogeneic SCT and referred for transplant evaluation as early as possible following diagnosis.[12][15][71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

OR

decitabine

OR

decitabine/cedazuridine

OR

ivosidenib

Secondary options

romiplostim

Plus – supportive care

Back
ACUTE
|
lower-risk disease: with clinically relevant thrombocytopenia or neutropenia (without symptomatic anemia)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Platelet transfusions are recommended for thrombocytopenic bleeding.[15] Platelet transfusions should not be used routinely in patients with thrombocytopenia in the absence of bleeding unless platelet count is <10,000/microliter.[15]

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

higher-risk disease: transplant candidate

1st line – allogeneic stem cell transplant (SCT)

Back
ACUTE
|
higher-risk disease: transplant candidate
1st line – 

allogeneic stem cell transplant (SCT)

Patients with higher-risk disease (e.g., intermediate, high, or very-high risk according to the Revised International Prognostic Scoring System [IPSS-R]) have a poor prognosis (relatively increased risk of progression to acute myeloid leukemia [AML] or death).[12][15]

Treatment for higher-risk patients is focused on delaying progression and prolonging survival, reducing symptoms and complications, and improving quality of life.

Higher-risk patients should be promptly referred for allogeneic SCT evaluation.[12][83][84]​​ Patients should be encouraged to enroll in a clinical trial (if available and eligible), especially if they have poor prognostic markers (e.g., TP53 mutations).

Higher-risk patients may undergo immediate allogeneic SCT if suitable (e.g., based on age, performance status, comorbidities, patient preference, and donor availability).[12][15]

Pre-transplant cytoreduction (debulking) using chemotherapy or hypomethylating agents (azacitidine, decitabine, decitabine/cedazuridine) is recommended to reduce marrow blasts to <5% in patients with high tumor burden.[12][15][54]

Ivosidenib can be used for cytoreduction if there is no response to chemotherapy or hypomethylating agents, and the patient has IDH1​ mutations.[15] Cytoreduction may reduce the risk of post-transplant relapse. However, this has not yet been confirmed by prospective clinical trials.

Allogeneic SCT is the only potentially curative therapy for MDS.[71]

A matched sibling donor, unrelated donor, haploidentical donor, or cord blood donor can be used for allogeneic SCT.[71] Standard or reduced-intensity conditioning regimens may be considered.[71]

Plus – supportive care

Back
ACUTE
|
higher-risk disease: transplant candidate
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

All symptomatic patients should receive supportive care as appropriate.

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Platelet transfusions are recommended for thrombocytopenic bleeding.[15] Platelet transfusions should not be used routinely in patients with thrombocytopenia in the absence of bleeding unless platelet count is <10,000/microliter.[15]

All transfused blood products should be irradiated before use in patients who are potential candidates for allogeneic SCT.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

Patients who have undergone allogeneic SCT should receive antibiotic prophylaxis alongside post-transplant immunosuppressive regimens used to manage graft-versus-host disease.

higher-risk disease: nontransplant candidate

1st line – clinical trial or hypomethylating agent

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ACUTE
|
higher-risk disease: nontransplant candidate
1st line – 

clinical trial or hypomethylating agent

Patients with higher-risk disease (e.g., intermediate, high, or very-high risk according to the Revised International Prognostic Scoring System [IPSS-R]) have a poor prognosis (relatively increased risk of progression to acute myeloid leukemia [AML] or death).[12][15]

Treatment for higher-risk patients is focused on delaying progression and prolonging survival, reducing symptoms and complications, and improving quality of life.

Higher-risk patients should be promptly referred for allogeneic stem cell transplantation (SCT) evaluation.[12][83][84]​ Patients should also be encouraged to enrol in a clinical trial (if available and eligible), especially if they have poor prognostic markers (e.g., TP53 mutations).

Higher-risk patients who are unsuitable for allogeneic SCT can be considered for a clinical trial or initial treatment with a hypomethylating agent (azacitidine [preferred]; decitabine; or decitabine/cedazuridine).[12][15][85]

Azacitidine improves overall survival in higher-risk patients compared with supportive care and chemotherapy.[86]​ A survival benefit with decitabine has not been shown in phase 3 trials, but a US-based registry study suggested similar survival to azacitidine.[87]

In patients with higher-risk disease, treatment with a hypomethylating agent should continue until the patient stops responding or treatment becomes intolerable.

See local specialist protocol for dosing guidelines.

Primary options

azacitidine

Secondary options

decitabine

OR

decitabine/cedazuridine

Plus – supportive care

Back
ACUTE
|
higher-risk disease: nontransplant candidate
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

All symptomatic patients should receive supportive care as appropriate.

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15]​ Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level.

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Platelet transfusions are recommended for thrombocytopenic bleeding.[15] Platelet transfusions should not be used routinely in patients with thrombocytopenia in the absence of bleeding unless platelet count is <10,000/microliter.[15]

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15]

2nd line – ivosidenib or clinical trial

Back
ACUTE
|
higher-risk disease: nontransplant candidate
2nd line – 

ivosidenib or clinical trial

Patients with higher-risk disease who do not respond to initial treatment with a hypomethylating agent can be treated with ivosidenib if they have IDH1​ mutations, or considered for a clinical trial if they do not have IDH1​ mutations.[15]

See local specialist protocol for dosing guidelines.

Primary options

ivosidenib

Plus – supportive care

Back
ACUTE
|
higher-risk disease: nontransplant candidate
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

All symptomatic patients should receive supportive care as appropriate.

Red blood cell (RBC) transfusion (with iron chelation therapy supported if needed) is recommended for symptomatic anemia.[15] Patients should be transfused with the minimum number of units necessary to relieve symptoms of anemia or to return the patient to a safe hemoglobin level. 

RBC transfusions are usually warranted if hemoglobin falls below 7 g/dL or 8 g/dL.[12][70]​ However, transfusions should be individualized because symptomatic anemia may occur at higher hemoglobin levels.

Platelet transfusions are recommended for thrombocytopenic bleeding.[15] Platelet transfusions should not be used routinely in patients with thrombocytopenia in the absence of bleeding unless platelet count is <10,000/microliter.[15] 

Antibiotics are recommended for bacterial infections and prophylaxis may be considered when starting patients on therapy; consult local guidance.[15] 

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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