NCT01736683

Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)

Completed Phase 2 Results posted Last updated 24 October 2022

What this trial tests

Phase 2 trial testing Sotatercept in Anemia in 74 participants. Completed in 30 April 2018.

Timeline

28 November 2012

Primary endpoint
30 April 2018

30 April 2018

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	74
Start date	28 November 2012
Primary completion	30 April 2018
Estimated completion	30 April 2018
Sites	20 locations across France, United States

Drugs / interventions tested

• Sotatercept (SOTATERCEPT) — full drug profile →

Conditions studied

• Anemia — all drugs for Anemia →
• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →
• Chronic Myelomonocytic Leukemia — all drugs for Chronic Myelomonocytic Leukemia →
• Low to Intermediate-1 MDS — all drugs for Low to Intermediate-1 MDS →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Anemia or Myelodysplastic Syndromes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate) Primary · Day 2 to Day 142

The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For transfusion dependence efficacy (TDE) participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days ove

All participants

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	66.7
Sotatercept 0.5 mg/kg	42.9
Sotatercept 1.0 mg/kg	60.0
Sotatercept 2.0 mg/kg	40.0

NTDE subpopulation

Group	Value	95% CI
Sotatercept 0.5 mg/kg	33.3
Sotatercept 1.0 mg/kg	62.5
Sotatercept 2.0 mg/kg	100

TDE subpopulation

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	66.7
Sotatercept 0.5 mg/kg	44.4
Sotatercept 1.0 mg/kg	59.3
Sotatercept 2.0 mg/kg	25.0

Time to Erythroid Hematological Improvement (HI-E) Response Secondary · Day 1 to Day 87

Time to first response = start date of first response (HI-E) - first dose date + 1 day. For NTDE participants (who required \< 4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For TDE participants (who required \>=4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.

All participants

Group	Value	95% CI
Sotatercept 0.3 mg/kg	24.0	2 – 44
Sotatercept 0.5 mg/kg	1.0	1 – 2
Sotatercept 1.0 mg/kg	1.0	1 – 86
Sotatercept 2.0 mg/kg	48	9 – 87

NTDE subpopulation

Group	Value	95% CI
Sotatercept 0.5 mg/kg	1.0	1 – 1
Sotatercept 1.0 mg/kg	1.0	1 – 52
Sotatercept 2.0 mg/kg	9.0	9 – 9

TDE subpopulation

Group	Value	95% CI
Sotatercept 0.3 mg/kg	24.0	2 – 44
Sotatercept 0.5 mg/kg	1.5	1 – 2
Sotatercept 1.0 mg/kg	1.5	1 – 86
Sotatercept 2.0 mg/kg	87	87 – 87

Duration of Erythroid Hematological Improvement (HI-E) Secondary · Day 1 to 183.7 weeks

The duration of HI-E response for participants who responded was (the last date of the consecutive hemoglobin \[Hgb\] measurements of the first \>=56 day interval) - (the first date of the consecutive Hgb measurements of the first \>=56 day interval) + 1 day.

All participants

Group	Value	95% CI
Sotatercept 0.3 mg/kg	62.5	62 – 69
Sotatercept 0.5 mg/kg	104.0	56 – 1794
Sotatercept 1.0 mg/kg	133.0	58 – 1554
Sotatercept 2.0 mg/kg	96.0	58 – 134

NTDE subpopulation

Group	Value	95% CI
Sotatercept 0.5 mg/kg	79.0	79 – 79
Sotatercept 1.0 mg/kg	1043.0	69 – 1554
Sotatercept 2.0 mg/kg	134.0	134 – 134

TDE subpopulation

Group	Value	95% CI
Sotatercept 0.3 mg/kg	62.5	62 – 69
Sotatercept 0.5 mg/kg	105.5	56 – 1794
Sotatercept 1.0 mg/kg	96.5	58 – 1033
Sotatercept 2.0 mg/kg	58.0	58 – 58

Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression Secondary · Day 1 to 183.7 weeks

Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - \>=50% increase in blasts - \>=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in Hgb concentration by \>=2 g/dL - Transfusion dependence This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Disclosed are time to progression values only for participants who did progress to AML.

Group	Value	95% CI
Sotatercept 0.5 mg/kg	45.6
Sotatercept 1.0 mg/kg	78.0

Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression Secondary · Day 1 to 257.3 weeks

Progression to events of higher risk MDS used criteria from the International Prognostic Scoring System for MDS (IPSS) which assigns a prognostic score (0=good and increasing in risk by half-grades with the top score outlined below) for three prognostic variables: - Marrow blasts (score 0-2.0) - Karyotype (score 0-1.0) - Cytopenias: neutrophil, platelets, and Hg counts (score 0-0.5) The three individual scores are summed resulting in a full range of 0- 3.5 and placed into risk categories 0 = low risk 0.5-1.0 = intermediate-1 risk 1.5-2.0 = intermediate-2 risk \>=2.5 = high risk This outcome wa

Group	Value	95% CI
Sotatercept 0.1 mg/kg	15.1
Sotatercept 0.5 mg/kg	24.7
Sotatercept 1.0 mg/kg	67.4

Kaplan-Meier Estimates for Progression-free Survival Secondary · Day 1 to 257.3 weeks

Participants who had disease progression were considered to have events. Participants who died without acute myeloid leukemia (AML) were also considered to have events with the event date as the date of death. Those who did not have disease progression and who were lost to follow-up were censored at the last known disease progression assessment date. Participants without disease progression at the last follow-up contact were censored at the date of the last follow-up contact date. Disease Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodyspla

Group	Value	95% CI
Sotatercept 0.1 mg/kg	82.7	15.1 – 82.7
Sotatercept 0.3 mg/kg	NA	91.1 – NA
Sotatercept 0.5 mg/kg	NA	58.6 – NA
Sotatercept 1.0 mg/kg	NA	NA – NA
Sotatercept 2.0 mg/kg	NA	79.9 – NA

Kaplan-Meier Estimates for Overall Survival (OS) Secondary · Day 1 to 257.3 weeks

OS was defined as the time between start of treatment and the death/censored date. Participants who died (regardless of the cause of death) were considered to have an event. Participants who were alive at the end of the study, and participants who were lost to follow-up, were censored at the last date when subjects were known to be alive.

Group	Value	95% CI
Sotatercept 0.1 mg/kg	82.7	NA – NA
Sotatercept 0.3 mg/kg	NA	91.00 – NA
Sotatercept 0.5 mg/kg	NA	58.6 – NA
Sotatercept 1.0 mg/kg	NA	NA – NA
Sotatercept 2.0 mg/kg	NA	79.1 – NA

Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints Secondary · Cycle 1 Day 8 and !5 up to Cycle 2 Day 1

Maximum observed serum concentration, obtained directly from the observed concentration versus time data.

Cycle 1 Day 8

Group	Value	95% CI
Sotatercept 0.1 mg/kg	288.06	± 70.94
Sotatercept 0.3 mg/kg	1426.00	± 27.76
Sotatercept 0.5 mg/kg	2237.46	± 40.77
Sotatercept 1.0 mg/kg	6525.37	± 28.31
Sotatercept 2.0 mg/kg	12886.14	± 30.47

Cycle 1 Day 15

Group	Value	95% CI
Sotatercept 0.1 mg/kg	240.31	± 75.32
Sotatercept 0.3 mg/kg	1207.68	± 16.14
Sotatercept 0.5 mg/kg	1869.52	± 36.97
Sotatercept 1.0 mg/kg	5149.74	± 36.04
Sotatercept 2.0 mg/kg	8303.73	± 43.57

Cycle 2 Day 1

Group	Value	95% CI
Sotatercept 0.1 mg/kg	252.20	± 28.43
Sotatercept 0.3 mg/kg	957.58	± 18.63
Sotatercept 0.5 mg/kg	1323.91	± 44.40
Sotatercept 1.0 mg/kg	3467.58	± 57.06
Sotatercept 2.0 mg/kg	5329.63	± 38.27

Participants With Treatment-Emergent Adverse Events (TEAE) Secondary · Day 1 up to 59.2 months

An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first treatment of the study medication and within 42 days after the last dose. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0 and the scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. Relation to study d

>= 1 Treatment-emergent adverse event (TEAE)

Group	Value	95% CI
Sotatercept 0.1 mg/kg	6
Sotatercept 0.3 mg/kg	4
Sotatercept 0.5 mg/kg	20
Sotatercept 1.0 mg/kg	34
Sotatercept 2.0 mg/kg	5

>=1 Treatment-related TEAE

Group	Value	95% CI
Sotatercept 0.1 mg/kg	2
Sotatercept 0.3 mg/kg	3
Sotatercept 0.5 mg/kg	7
Sotatercept 1.0 mg/kg	18
Sotatercept 2.0 mg/kg	4

>=1 Serious TEAE

Group	Value	95% CI
Sotatercept 0.1 mg/kg	1
Sotatercept 0.3 mg/kg	2
Sotatercept 0.5 mg/kg	6
Sotatercept 1.0 mg/kg	10
Sotatercept 2.0 mg/kg	2

>=1 Serious TEAE related to treatment

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	0
Sotatercept 1.0 mg/kg	0
Sotatercept 2.0 mg/kg	1

>=1 TEAE severity 3 or 4

Group	Value	95% CI
Sotatercept 0.1 mg/kg	1
Sotatercept 0.3 mg/kg	2
Sotatercept 0.5 mg/kg	9
Sotatercept 1.0 mg/kg	13
Sotatercept 2.0 mg/kg	2

>=1 TEAE severity grade 3/4 related to treatment

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	1
Sotatercept 1.0 mg/kg	0
Sotatercept 2.0 mg/kg	1

>=1 TEAE leading to death

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	1
Sotatercept 0.5 mg/kg	0
Sotatercept 1.0 mg/kg	0
Sotatercept 2.0 mg/kg	0

>=1 TEAE leading to dose reduction

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	0
Sotatercept 1.0 mg/kg	0
Sotatercept 2.0 mg/kg	0

Dose Limiting Toxicities (DLTs) Secondary · Day 1 to 59.2 months

The following were DLTs if the investigator suspected they were treatment related: 1. Increase to \>= 140 mmHg systolic blood pressure 2. Increase to \>=90 mmHg diastolic blood pressure 3. Increase to \>=140 systolic and increase \> 20 mmHg compared to baseline systolic 4. Increase to \>=90 mmHg diastolic and increase \> 20 mmHg compared to baseline diastolic 5. Introduction of new anti-hypertension medication during treatment 6. Increase in dose of baseline anti-hypertension medication during treatment 7. \>= Grade 2 (moderate severity or worse) hypertension as an adverse event

1. Increase to >= 140 mmHg systolic

Group	Value	95% CI
Sotatercept 0.1 mg/kg	1
Sotatercept 0.3 mg/kg	1
Sotatercept 0.5 mg/kg	8
Sotatercept 1.0 mg/kg	19
Sotatercept 2.0 mg/kg	2

2. Increase to >=90 mmHg diastolic

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	2
Sotatercept 1.0 mg/kg	2
Sotatercept 2.0 mg/kg	1

3. =140 systolic and increase > 20 mmHg base

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	1
Sotatercept 0.5 mg/kg	5
Sotatercept 1.0 mg/kg	10
Sotatercept 2.0 mg/kg	2

4. >=90 mmHg diastolic and increase > 20 mmHg base

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	2
Sotatercept 1.0 mg/kg	2
Sotatercept 2.0 mg/kg	1

5. Introduction of new anti-hypertension med

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	4
Sotatercept 1.0 mg/kg	3
Sotatercept 2.0 mg/kg	1

6. Incre in dose of baseline anti-hypertension med

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	0
Sotatercept 1.0 mg/kg	0
Sotatercept 2.0 mg/kg	0

7.>= Grade 2 hypertension TEAE

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	1
Sotatercept 0.5 mg/kg	2
Sotatercept 1.0 mg/kg	4
Sotatercept 2.0 mg/kg	1

Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval Secondary · Day 2 to Day 142

Number of participants who achieved RBC-independence was defined as participants who required no RBC-transfusions during a 56-day interval of erythroid hematological improvement (HI-E). NTDE = non-transfusion dependence efficacy participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy TDE = transfusion dependence efficacy participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy

All participants

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	1
Sotatercept 0.5 mg/kg	3
Sotatercept 1.0 mg/kg	15
Sotatercept 2.0 mg/kg	1

NTDE subpopulation

Group	Value	95% CI
Sotatercept 0.5 mg/kg	1
Sotatercept 1.0 mg/kg	6
Sotatercept 2.0 mg/kg	1

TDE subpopulation

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0
Sotatercept 0.3 mg/kg	1
Sotatercept 0.5 mg/kg	2
Sotatercept 1.0 mg/kg	9
Sotatercept 2.0 mg/kg	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 up to 60.7 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sotatercept 0.1 mg/kg

Serious: 1/7 (14%)

Deaths: 1/7

Sotatercept 0.3 mg/kg

Serious: 2/6 (33%)

Deaths: 1/6

Sotatercept 0.5 mg/kg

Serious: 6/21 (29%)

Deaths: 6/21

Sotatercept 1.0 mg/kg

Serious: 10/35 (29%)

Deaths: 6/35

Sotatercept 2.0 mg/kg

Serious: 2/5 (40%)

Deaths: 1/5

Serious adverse events (33 terms)

Reaction	System	Sotatercept 0.1 mg/kg	Sotatercept 0.3 mg/kg	Sotatercept 0.5 mg/kg	Sotatercept 1.0 mg/kg	Sotatercept 2.0 mg/kg
Colitis	Gastrointestinal disorders	—	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—
Large intestine perforation	Gastrointestinal disorders	—	—	—	—	—
Mass	General disorders	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Cholangitis	Hepatobiliary disorders	—	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—
Clostridium difficile colitis	Infections and infestations	—	—	—	—	—
Escherichia pyelonephritis	Infections and infestations	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—
Peritoneal abscess	Infections and infestations	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Spinal compression fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Spinal fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—	—	—	—
Transfusion reaction	Injury, poisoning and procedural complications	—	—	—	—	—
Blood pressure increased	Investigations	—	—	—	—	—
International normalised ratio increased	Investigations	—	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—

Other adverse events (110 terms — click to expand)

Reaction	System	Sotatercept 0.1 mg/kg	Sotatercept 0.3 mg/kg	Sotatercept 0.5 mg/kg	Sotatercept 1.0 mg/kg	Sotatercept 2.0 mg/kg
Fatigue	General disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Face oedema	General disorders	—	—	—	—	—
Influenza like illness	General disorders	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—

Most-reported serious reactions: Colitis, Hip fracture, Anaemia, Angina pectoris, Large intestine perforation, Mass, Non-cardiac chest pain, Pyrexia.

Data from ClinicalTrials.gov NCT01736683 adverse events section.

Sponsor's own description

The primary objective of this study is to determine a safe, tolerable and effective dose of sotatercept that results in the greatest frequency of improvement of anemia in patients diagnosed with low- or intermediate-1 risk myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.
   Herbertz S, Sawyer JS, Stauber AJ, Gueorguieva I, et al · · 2015 · cited 424× · PMID 26309397 · DOI 10.2147/dddt.s86621
2. Anemia: progress in molecular mechanisms and therapies.
   Sankaran VG, Weiss MJ. · · 2015 · cited 200× · PMID 25742458 · DOI 10.1038/nm.3814
3. Bone morphogenetic protein receptor signal transduction in human disease.
   Gomez-Puerto MC, Iyengar PV, García de Vinuesa A, Ten Dijke P, et al · · 2019 · cited 172× · PMID 30246251 · DOI 10.1002/path.5170
4. TGF-beta signal transduction: biology, function and therapy for diseases.
   Tie Y, Tang F, Peng D, Zhang Y, et al · · 2022 · cited 97× · PMID 36534225 · DOI 10.1186/s43556-022-00109-9
5. Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial.
   Komrokji R, Garcia-Manero G, Ades L, Prebet T, et al · · 2018 · cited 91× · PMID 29331635 · DOI 10.1016/s2352-3026(18)30002-4
6. Myelodysplasia is in the niche: novel concepts and emerging therapies.
   Bulycheva E, Rauner M, Rauner M, Medyouf H, et al · · 2015 · cited 62× · PMID 25394715 · DOI 10.1038/leu.2014.325
7. The role of TGFβ in hematopoiesis and myeloid disorders.
   Bataller A, Montalban-Bravo G, Soltysiak KA, Garcia-Manero G. · · 2019 · cited 57× · PMID 30816330 · DOI 10.1038/s41375-019-0420-1
8. Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T): 2017 update on diagnosis, risk-stratification, and management.
   Patnaik MM, Tefferi A. · · 2017 · cited 45× · PMID 28188970 · DOI 10.1002/ajh.24637