MDS Foundation ASH Summaries 2025

Research helps us find cures for MDS. In early December 2025, doctors who study MDS came together in Orlando, Florida for the yearly meeting of the American Society of Hematology (ASH). At this meeting, more than 8,000 research projects were shared, including many focused on myelodysplastic syndromes (MDS). Below is a summary of some of these studies. To see more projects, you can visit the ASH website by clicking here.

Low Risk MDS

Abstract 787. Chee L, et al. Elritercept shows durable responses in lower-risk myelodysplastic neoplasms (LR-MDS) with transfusion dependence: Updated Results from an ongoing Phase 2 trial.

What’s being studied: Elritercept is a new medicine being tested to help people with lower‑risk myelodysplastic syndromes (LR‑MDS) who need frequent blood transfusions.
Trial details: In a Phase 2 study, 78 patients were treated with elritercept, an investigational, modified activin receptor type IIA/IgG1 fusion protein designed to bind and block select TGF-β superfamily ligands (activins A & B, GDF 8 & 11). Doctors looked at whether patients could go without transfusions and if their blood counts improved.
Results: About 39% of patients stopped needing transfusions for at least 8 weeks, and about 27% stayed transfusion‑free for 24 weeks. Many kept this benefit for almost a year.
Response time: Some patients saw results very quickly—within days to weeks. Overall, 62% had better red blood cell levels.
Genetics: A common gene change called SF3B1 was found in many patients. Those with this mutation responded more often (52%) than those without it (25%).
Next steps: Because of these promising results, a larger Phase 3 study (RENEW, NCT06499285) is now underway to confirm if elritercept can become a new treatment option.

Abstract 789 Zeiden A, et al: Luspatercept initiated at the maximum-approved dose in transfusion-dependent lower-risk myelodysplastic syndromes: Interim analysis from MAXILUS

What’s being studied: Luspatercept (Reblozyl) is a medicine already approved to help people with lower‑risk MDS who need blood transfusions. This study (MAXILUS) tested starting patients right away at the highest approved dose (1.75 mg/kg)
Who was in the study: 105 low-risk patients (without del5q) took part. All patients required at least 1 unit of red blood cell transfusions every 8 weeks before study entry. Some had never used ESA drugs before, while others had tried them but stopped because they didn’t work or caused problems.
Results for ESA‑naive patients: About 73% of patients went at least 8 weeks without needing transfusions, and 70% stayed transfusion‑free for 12 weeks. Benefits were stronger in patients with lower erythropoietin levels (<200 IU/L).
Results for ESA‑experienced patients: About 65% went at least 8 weeks without transfusions, and nearly half stayed transfusion‑free for 12 weeks.
Safety: Luspatercept was generally safe. Most side effects were mild to moderate, and no patients developed leukemia.
Conclusion: Starting luspatercept at the full dose worked well and was safe, especially for patients who had never used ESA drugs before.

Abstract 790 Garcia-Manero G, et al: Low-dose oral decitabine and cedazuridine among patients with low-risk myelodysplastic syndromes

What’s being studied: Injections of azacytidine and decitabine at lower doses are occasionally recommended for low-risk MDS. Doctors tested two versions of an oral medicine (INQOVI), which is approved for high-risk MDS in patients with lower‑risk MDS. One version was an experimental low‑dose (LD) given over 5‑days, and the other was the standard‑dose (SD) (commercially available dose) given over 3‑days.
Who was in the study: 81 patients took part in this study (ASTX727-03; NCT03502668), most in their 70s, all with lower‑risk MDS and low blood counts.
Results: Both groups had similar improvements in blood counts, at 27% in both treatment arms. About half of the patients who were previously transfusion dependent on the LD plan became transfusion‑independent for at least 2 months, compared to about one‑third on the SD plan.
Safety: Side effects like anemia, fatigue, and low platelets were common in both groups. Serious side effects were less frequent with the LD plan, and fewer patients had to stop treatment because of problems.
Survival: Overall survival and leukemia‑free survival were similar between the two groups (about 2 years).
Conclusion: The LD oral regimen worked as well as the SD regimen but was safer and easier to tolerate, making it a promising option for patients with lower‑risk MDS.

Abstract 792 Santini V, et al: Clinical benefit of luspatercept in erythropoiesis-stimulating agent (ESA)-naive patients (pts) with early disease characteristics and very low-, low-, or intermediate-risk Myelodysplastic Syndromes (LR-MDS): A post hoc analysis from the commands trial

What’s being studied: The COMMANDS trial (NCT03682536) compared two medicines—luspatercept and epoetin alfa (EA)—to help people with lower‑risk MDS who need blood transfusions. Previously luspatercept (Reblozyl) was found to be superior to ESAs in the entire study cohort, but it was unknown how patients with early disease characteristics compared.
Who was in the study: Over 360 patients took part. They had never used ESA drugs (such as Epogen, Procrit, and Aranesp) and all needed regular transfusions. Patients were split into groups with hemoglobin >8 or <8 gm/dL; transfusion burden =2 or >4 units blood; epo level <100 or >200)
Results: Luspatercept helped more patients go without transfusions for at least 12 weeks compared to EA, and the benefit lasted longer.
Disease stage matters: Patients with less severe disease (higher hemoglobin, fewer transfusions, lower erythropoietin levels) responded better to both medicines, but Luspatercept worked better than EA in all groups.
Consistency: No matter the disease stage, luspatercept gave patients at least twice the chance of becoming transfusion‑independent compared to EA.
Conclusion: Luspatercept was more effective than EA, supporting its use in patients with lower‑risk MDS who need transfusions.

Abstract 487 Bouligny I, et al: A randomized, multicenter trial of shorter durations of hypomethylating agents in lower-risk Myelodysplastic Syndromes

What’s being studied: Doctors tested shorter courses of azacitidine and decitabine (3 or 5 days) in patients with lower‑risk MDS, to see if they worked as well as standard longer treatments but with fewer side effects. (Standard dosing in higher-risk MDS is 5-7 days)
Who was in the study: 247 patients took part, average age about 71. They were split into transfusion‑dependent and transfusion‑independent groups. (NCT02269280). The median IPSS-R score was 3.
Results in transfusion‑dependent patients: Response rates were similar across all regimens (about 48–53%), and around 40–44% became transfusion‑independent.
Results in transfusion‑independent patients: The best responses came with 5‑day azacitidine (70%), compared to 50% with 3‑day regimens and only 17% with supportive care. Responses also lasted longer with 5‑day azacitidine.
Overall survival rates were highest in the 5-day azacitidine groups in the Cox models.
Safety: Serious low platelet counts were more common with decitabine than with azacitidine. Early death rates were low (1–2%).
Conclusion: Shorter HMA courses are safe and effective in lower‑risk MDS, but 5‑day azacitidine gave the most consistent survival and event‑free survival benefit, making it the best balance of safety and efficacy

Abstract 489 Garcia-Manero G, et al: Safety and efficacy results from A phase 1b study of R289, a dual irak 1/4 inhibitor, in patients with Relapsed/Refractory (R/R) lower risk myelodysplastic syndrome (LR-MDS).

What’s being studied: The experimental medication R289 (a pill that turns into R835 in the body) blocks inflammation signals that may drive MDS. It was tested with different doses in patients with lower‑risk MDS (IPSS-R <3.5) who had already tried several treatments (NCT05308264).
Who was in the study: 33 patients, average age 75. Most had already received luspatercept, ESAs, or hypomethylating agents. Nearly all were transfusion‑dependent, with many needing high numbers of transfusions.
Safety: The drug was generally well‑tolerated. Common side effects were mild (like diarrhea, constipation, fatigue). Serious side effects were less frequent, including anemia and infections. Only 2 patients stopped treatment because of side effects.
Responses: At doses of 500 mg/day or higher, about 31% of patients became transfusion‑independent for at least 8 weeks, with some lasting over a year. One patient also had a marrow complete response. Lower doses did not show benefit.
Dose effect: Blood levels of R835 at ≥500 mg/day matched those needed to block inflammatory signals in lab tests, suggesting this is the threshold for activity.
Conclusion: R289 looks safe and shows early signs of benefit in heavily pretreated, transfusion‑dependent LR‑MDS patients. Ongoing trials will compare doses to find the best one for future studies

Abstract 490 Zeiden A, et al: Correlation between treatment-emergent cytopenias and clinical response with imetelstat (IME) in patients (Pts) with lower-risk myelodysplastic syndromes (LR-MDS): Analysis from the imerge Trial

What’s being studied: IME (Rytelo) is a telomerase inhibitor approved for lower‑risk MDS patients who depend on transfusions and don’t respond to other drugs. The imerge trial previously demonstrated improved transfusion independence lasting 8 or more weeks with IME compared to placebo (40% vs 15%). This analysis looked at whether blood count drops (cytopenias) during treatment were linked to better outcomes.
Who was in the study: 226 patients, average age 71, with low hemoglobin at the start. They received IME for a median of 34 weeks. (NCT02598661)
Results with platelet drops: Patients whose platelets fell by ≥50% in the first 2 cycles had bigger hemoglobin increases, higher rates of hematologic improvement, and more long‑term transfusion independence compared to those with smaller drops.
Results with neutrophil drops: Patients whose neutrophils fell by ≥75% in the first 2 cycles also had larger hemoglobin increases, though transfusion independence rates were similar to those with smaller drops.
Key driver: The size of hemoglobin increase was the strongest predictor of achieving transfusion independence for 8 or 24 weeks.
Conclusion: Cytopenias (low platelets or neutrophils) caused by IME may signal that the drug is working, leading to better blood production and transfusion independence. Thus, patients should be encouraged continue treatment with IME despite worsening early cytopenias.

Abstract 492 Mei C, et al: Hetrombopag for the treatment of lower-risk myelodysplastic syndromes with thrombocytopenia: A prospective, single-arm, multicenter study

What’s being studied: Hetrombopag is a new experimental pill that stimulates platelet production. It was tested in patients with lower‑risk MDS who had very low platelet counts, a group at high risk of bleeding.
Who was in the study: 43 patients, average age 57, most with intermediate‑risk disease and low‑blast MDS (<5%). All had platelet counts ≤30×10⁹/L at the start. Prior studies with other platelet-stimulating agents in MDS patients have been complicated by worsening blast counts.
Results: About 42% of patients had a platelet response, including 7% with complete responses. Nearly 28% reached platelet counts above 50×10⁹/L. Responses usually appeared within 7 weeks.
Predictors: Response did not depend on age, gender, risk category, MDS subtype, performance status, or gene mutations.
Safety: Side effects occurred in 30% of patients, mostly infections. Serious infections happened in about 9%, but no treatment‑related deaths were reported.
Conclusion: Hetrombopag safely raised platelet counts in LR‑MDS patients with thrombocytopenia, showing promise as a new treatment option.

High Risk MDS

Abstract 235 Garcia-Manero G, et al: Subgroup analyses from the randomized, Phase 3 VERONA study of venetoclax with azacitidine (Ven+Aza) versus placebo with azacitidine (Pbo+Aza) in patients with treatment-naïve, intermediate and higher-risk Myelodysplastic Syndromes (HR MDS)

What’s being studied: The VERONA trial (NCT04401748) tested venetoclax plus azacitidine (Ven+Aza) against placebo plus azacitidine (Pbo+Aza) in patients with high‑risk MDS who had never been treated before.
Who was in the study: 509 patients took part, most in their early 70s. Both groups had similar disease risks and gene mutations. Patients had an IPSS-R score >3 (intermediate, high or very high risk).
Results: Overall survival was about the same between Ven+Aza and Pbo+Aza (around 22 months). However, Ven+Aza led to more overall responses (76% vs 58%) and fewer patients progressed to AML (15% vs 20%).
Subgroups: Younger patients, those with more blasts in their bone marrow, and patients with certain gene mutations (like TP53, ASXL1, RUNX1) showed trends of better response with Ven+Aza.
Treatment outcomes: More patients on Ven+Aza achieved marrow remission with blood count improvement compared to Pbo+Aza (27% vs 18%).
Conclusion: While Ven+Aza did not improve survival compared to Pbo+Aza, it gave higher response rates and signs of benefit in some patient groups, supporting further study in high‑risk MDS.

Abstract 236 Zeiden A, et al: Efficacy, molecular and translational analysis of TP53-mutated HR-MDS with bexmarilimab and azacitidine: Updated results from the Bexmab Phase 1/2 study

What’s being studied: Bexmarilimab is an experimental medicine that helps the immune system fight MDS. It is a novel macrophage checkpoint inhibitor targeting Clever-1, a scavenger receptor expressed on malignant blasts and monocytes. It was tested with azacitidine in patients with high‑risk MDS, especially those with TP53 mutations (a gene change linked to poor outcomes).
Who was in the study: 53 high risk MDS patients (IPSS-R >3 score) joined—21 had never been treated before, and 32 had already tried hypomethylating agents (HMAs; such as azacytidine and decitabine) but their disease came back or didn’t respond.
Results in untreated patients: Response rates were high—78% in patients with TP53 mutations and 91% in those without. About half of patients with TP53 mutations had complete responses.
Results in relapsed/refractory patients: Responses were lower—46% in TP53‑mutated patients and 74% in those without. Median survival was about 13 months overall, but shorter (9 months) in the TP53‑mutated group.
Immune effects: Lab studies showed stronger immune activity in the bone marrow, with more “killer” T cells and better antigen presentation after treatment.
Conclusion: Bexmarilimab plus azacitidine looks promising for patients with TP53‑mutated high‑risk MDS, a group with very limited options.

Abstract 237 Bataller A, et al: Oral decitabine/cedazuridine in combination with venetoclax in treatment-naïve high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia: Updates of a Phase 1/2 clinical trial

What’s being studied: Doctors tested a new combination of oral decitabine/cedazuridine (DEC‑C; INQOVI) with venetoclax (Ven) in patients with high‑risk MDS or CMML who had not been treated before (NCT04655755).
Who was in the study: 69 patients took part, most in their 70s. Patients had MDS with excess blasts or CMML. Many had gene changes linked to poor outcomes, including TP53 and ASXL1 mutations.
Results: The overall response rate was very high—91% by older criteria and 81% by newer criteria. Nearly half of patients achieved complete remission, often after just 1–3 treatment cycles.
Safety: Side effects included low blood counts (expected with this drug combination). Some patients needed dose reductions, and a few died from infections or other complications.
Transplant outcomes: Over half of patients (55%) went on to stem cell transplant, with many showing strong responses before transplant.
Survival: Median overall survival was 30 months, with about 55% of patients alive at 2 years. Patients with ASXL1 mutations lived longer, while those with TP53 mutations had shorter survival.

Abstract 238 Borate U, et al: Phase II study of clinical efficacy of venetoclax in combination with azacitidine in patients with therapy related myelodysplastic syndrome (t-MDS)

What’s being studied: Azacitidine plus venetoclax (Aza/Ven) was tested in patients with therapy‑related MDS, a very aggressive type of MDS that often has TP53 mutations and poor outcomes (NCT05379166).
Who was in the study: 23 patients were analyzed so far. Most were men, average age 67. Over 80% had TP53 mutations and/or complex genetic changes, making them very high‑risk. The IPSS-R scores were very high (>3.5)
Results: About 57% of patients responded to treatment, including 22% who achieved complete remission. Responses lasted a median of 12.7 months. Half of patients showed blood count improvements.
Disease outcomes: 39% of patients progressed to AML. Median survival was 10 months overall, but longer (about 15 months) in responders. About 30% of patients went on to stem cell transplant.
Safety: Almost all patients had serious side effects, mostly low blood counts leading to infections like sepsis or fever. Only one patient stopped treatment because of side effects.
Conclusion: Aza/Ven showed promising activity in this very high‑risk group, especially as a possible bridge to transplant, even though survival remains limited.

Abstract 239 Murthy GSG, et al: Hypomethylating agent with venetoclax versus hypomethylating agent alone in frontline management of myelodysplastic syndrome - impact of subgroups on clinical outcomes

What’s being studied: Doctors looked at how azacitidine or decitabine (HMAs) combined with venetoclax (VEN) worked in real‑world patients with high‑risk MDS, compared to HMA alone.
Who was in the study: 1,198 patients from 19 US academic centers. About 313 got HMA‑VEN, and 885 got HMA alone. Many had very‑high‑risk disease, therapy‑related MDS, or TP53 mutations. 75% had MDS with excess blasts. The study was retrospective and non-randomized, representing the doctor's choice in treatments (and thus may have biases).
Results: Response rates were much higher with HMA‑VEN (81% vs 39%). Complete remission was also better (17% vs 10%).
Survival: Patients on HMA‑VEN lived longer (median 22 months vs 18 months) and had fewer events like progression or death. Benefits were strongest in patients who later had a stem cell transplant, those with 10–19% blasts, de novo MDS, and those without TP53 mutations.
Genetics: The survival benefit of HMA‑VEN was also seen in patients with ASXL1 mutations, but not in those with TP53 mutations.
Conclusion: In real‑world practice (in contrast to the randomized Verona trial), HMA‑VEN improved outcomes for certain groups of high‑risk MDS patients.

Abstract 240 Braish J, et al: Durability of complete response outperforms complete response rates as a surrogate endpoint for advancing to phase III trials in high-risk myelodysplastic syndromes

What’s being studied: Doctors wanted to see if a durable complete response (lasting more than 6 months) is a better measure of benefit in high‑risk MDS than just achieving CR. Finding a good surrogate (early) endpoint is important for drug development, rather than waiting for survival results.
Who was in the study: 980 patients treated with hypomethylating agents (HMAs) at Moffitt Cancer Center. Median age was 72, and many had therapy‑related MDS.
Results: Patients who achieved CR lived longer (24 months vs 13 months for others). But only those with durable CR had a clear survival benefit. Short CRs (≤6 months) did not improve survival.
Treatment groups: CR rates were 12% with HMA alone, 12% with HMA+venetoclax, and 29% with HMA+novel agents. Durable CR occurred in about 10% of HMA patients, 9% of HMA+Ven patients, and 24% of those on novel agents.
Genetics: In patients with TP53 mutations, durable CR reduced risk of death by 38% with HMA alone, and by 73% when combined with eprenetapopt.
Conclusion: Only durable CR (lasting >6 months) truly improves survival in high‑risk MDS. This makes durable CR a more meaningful goal for new drug development than CR alone.

Abstract 491 Garcia-Manero G, et al: A phase 2 dose confirmation trial of oral ASTX030, a combination of oral azacitidine with cedazuridine among patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia

What’s being studied: ASTX030 is an experimental oral version of azacitidine (Vidaza) combined with cedazuridine. It aims to replace injections and reduce clinic visits for patients with MDS, CMML, or AML.
Who was in the study: 30 patients, average age 74, were treated. Most had MDS, with a few having CMML, AML, or MDS/MPN. (NCT04256317)
Results: Drug exposure with oral ASTX030 was similar to injected azacitidine overall, though body size affected levels. In MDS patients, 50% responded, with 23% achieving complete remission. About 31% of transfusion‑dependent patients became transfusion‑independent for at least 56 days.
Biology: DNA demethylation (a marker of drug activity) was comparable between oral and injected forms.
Safety: Side effects were common but mostly manageable. Nausea, constipation, and fatigue were frequent. Serious low blood counts (platelets, neutrophils, anemia) occurred in about one‑third to half of patients.
Conclusion: Oral ASTX030 worked similarly to injected azacitidine, with manageable safety. Adjusting doses by body size may improve consistency. A larger phase 3 trial (AZTOUND) is now recruiting.

Low Risk MDS

Abstract 787. Chee L, et al. Elritercept shows durable responses in lower-risk myelodysplastic neoplasms (LR-MDS) with transfusion dependence: Updated Results from an ongoing Phase 2 trial.

What’s being studied: Elritercept is a new medicine being tested to help people with lower‑risk myelodysplastic syndromes (LR‑MDS) who need frequent blood transfusions.
Trial details: In a Phase 2 study, 78 patients were treated with elritercept, an investigational, modified activin receptor type IIA/IgG1 fusion protein designed to bind and block select TGF-β superfamily ligands (activins A & B, GDF 8 & 11). Doctors looked at whether patients could go without transfusions and if their blood counts improved.
Results: About 39% of patients stopped needing transfusions for at least 8 weeks, and about 27% stayed transfusion‑free for 24 weeks. Many kept this benefit for almost a year.
Response time: Some patients saw results very quickly—within days to weeks. Overall, 62% had better red blood cell levels.
Genetics: A common gene change called SF3B1 was found in many patients. Those with this mutation responded more often (52%) than those without it (25%).
Next steps: Because of these promising results, a larger Phase 3 study (RENEW, NCT06499285) is now underway to confirm if elritercept can become a new treatment option.

Abstract 789 Zeiden A, et al: Luspatercept initiated at the maximum-approved dose in transfusion-dependent lower-risk myelodysplastic syndromes: Interim analysis from MAXILUS

What’s being studied: Luspatercept (Reblozyl) is a medicine already approved to help people with lower‑risk MDS who need blood transfusions. This study (MAXILUS) tested starting patients right away at the highest approved dose (1.75 mg/kg)
Who was in the study: 105 low-risk patients (without del5q) took part. All patients required at least 1 unit of red blood cell transfusions every 8 weeks before study entry. Some had never used ESA drugs before, while others had tried them but stopped because they didn’t work or caused problems.
Results for ESA‑naive patients: About 73% of patients went at least 8 weeks without needing transfusions, and 70% stayed transfusion‑free for 12 weeks. Benefits were stronger in patients with lower erythropoietin levels (<200 IU/L).
Results for ESA‑experienced patients: About 65% went at least 8 weeks without transfusions, and nearly half stayed transfusion‑free for 12 weeks.
Safety: Luspatercept was generally safe. Most side effects were mild to moderate, and no patients developed leukemia.
Conclusion: Starting luspatercept at the full dose worked well and was safe, especially for patients who had never used ESA drugs before.

Abstract 790 Garcia-Manero G, et al: Low-dose oral decitabine and cedazuridine among patients with low-risk myelodysplastic syndromes

What’s being studied: Injections of azacytidine and decitabine at lower doses are occasionally recommended for low-risk MDS. Doctors tested two versions of an oral medicine (INQOVI), which is approved for high-risk MDS in patients with lower‑risk MDS. One version was an experimental low‑dose (LD) given over 5‑days, and the other was the standard‑dose (SD) (commercially available dose) given over 3‑days.
Who was in the study: 81 patients took part in this study (ASTX727-03; NCT03502668), most in their 70s, all with lower‑risk MDS and low blood counts.
Results: Both groups had similar improvements in blood counts, at 27% in both treatment arms. About half of the patients who were previously transfusion dependent on the LD plan became transfusion‑independent for at least 2 months, compared to about one‑third on the SD plan.
Safety: Side effects like anemia, fatigue, and low platelets were common in both groups. Serious side effects were less frequent with the LD plan, and fewer patients had to stop treatment because of problems.
Survival: Overall survival and leukemia‑free survival were similar between the two groups (about 2 years).
Conclusion: The LD oral regimen worked as well as the SD regimen but was safer and easier to tolerate, making it a promising option for patients with lower‑risk MDS.

What’s being studied: The COMMANDS trial (NCT03682536) compared two medicines—luspatercept and epoetin alfa (EA)—to help people with lower‑risk MDS who need blood transfusions. Previously luspatercept (Reblozyl) was found to be superior to ESAs in the entire study cohort, but it was unknown how patients with early disease characteristics compared.
Who was in the study: Over 360 patients took part. They had never used ESA drugs (such as Epogen, Procrit, and Aranesp) and all needed regular transfusions. Patients were split into groups with hemoglobin >8 or <8 gm/dL; transfusion burden =2 or >4 units blood; epo level <100 or >200)
Results: Luspatercept helped more patients go without transfusions for at least 12 weeks compared to EA, and the benefit lasted longer.
Disease stage matters: Patients with less severe disease (higher hemoglobin, fewer transfusions, lower erythropoietin levels) responded better to both medicines, but Luspatercept worked better than EA in all groups.
Consistency: No matter the disease stage, luspatercept gave patients at least twice the chance of becoming transfusion‑independent compared to EA.
Conclusion: Luspatercept was more effective than EA, supporting its use in patients with lower‑risk MDS who need transfusions.

Abstract 487 Bouligny I, et al: A randomized, multicenter trial of shorter durations of hypomethylating agents in lower-risk Myelodysplastic Syndromes

What’s being studied: Doctors tested shorter courses of azacitidine and decitabine (3 or 5 days) in patients with lower‑risk MDS, to see if they worked as well as standard longer treatments but with fewer side effects. (Standard dosing in higher-risk MDS is 5-7 days)
Who was in the study: 247 patients took part, average age about 71. They were split into transfusion‑dependent and transfusion‑independent groups. (NCT02269280). The median IPSS-R score was 3.
Results in transfusion‑dependent patients: Response rates were similar across all regimens (about 48–53%), and around 40–44% became transfusion‑independent.
Results in transfusion‑independent patients: The best responses came with 5‑day azacitidine (70%), compared to 50% with 3‑day regimens and only 17% with supportive care. Responses also lasted longer with 5‑day azacitidine.
Overall survival rates were highest in the 5-day azacitidine groups in the Cox models.
Safety: Serious low platelet counts were more common with decitabine than with azacitidine. Early death rates were low (1–2%).
Conclusion: Shorter HMA courses are safe and effective in lower‑risk MDS, but 5‑day azacitidine gave the most consistent survival and event‑free survival benefit, making it the best balance of safety and efficacy

What’s being studied: The experimental medication R289 (a pill that turns into R835 in the body) blocks inflammation signals that may drive MDS. It was tested with different doses in patients with lower‑risk MDS (IPSS-R <3.5) who had already tried several treatments (NCT05308264).
Who was in the study: 33 patients, average age 75. Most had already received luspatercept, ESAs, or hypomethylating agents. Nearly all were transfusion‑dependent, with many needing high numbers of transfusions.
Safety: The drug was generally well‑tolerated. Common side effects were mild (like diarrhea, constipation, fatigue). Serious side effects were less frequent, including anemia and infections. Only 2 patients stopped treatment because of side effects.
Responses: At doses of 500 mg/day or higher, about 31% of patients became transfusion‑independent for at least 8 weeks, with some lasting over a year. One patient also had a marrow complete response. Lower doses did not show benefit.
Dose effect: Blood levels of R835 at ≥500 mg/day matched those needed to block inflammatory signals in lab tests, suggesting this is the threshold for activity.
Conclusion: R289 looks safe and shows early signs of benefit in heavily pretreated, transfusion‑dependent LR‑MDS patients. Ongoing trials will compare doses to find the best one for future studies

What’s being studied: IME (Rytelo) is a telomerase inhibitor approved for lower‑risk MDS patients who depend on transfusions and don’t respond to other drugs. The imerge trial previously demonstrated improved transfusion independence lasting 8 or more weeks with IME compared to placebo (40% vs 15%). This analysis looked at whether blood count drops (cytopenias) during treatment were linked to better outcomes.
Who was in the study: 226 patients, average age 71, with low hemoglobin at the start. They received IME for a median of 34 weeks. (NCT02598661)
Results with platelet drops: Patients whose platelets fell by ≥50% in the first 2 cycles had bigger hemoglobin increases, higher rates of hematologic improvement, and more long‑term transfusion independence compared to those with smaller drops.
Results with neutrophil drops: Patients whose neutrophils fell by ≥75% in the first 2 cycles also had larger hemoglobin increases, though transfusion independence rates were similar to those with smaller drops.
Key driver: The size of hemoglobin increase was the strongest predictor of achieving transfusion independence for 8 or 24 weeks.
Conclusion: Cytopenias (low platelets or neutrophils) caused by IME may signal that the drug is working, leading to better blood production and transfusion independence. Thus, patients should be encouraged continue treatment with IME despite worsening early cytopenias.

Abstract 492 Mei C, et al: Hetrombopag for the treatment of lower-risk myelodysplastic syndromes with thrombocytopenia: A prospective, single-arm, multicenter study

What’s being studied: Hetrombopag is a new experimental pill that stimulates platelet production. It was tested in patients with lower‑risk MDS who had very low platelet counts, a group at high risk of bleeding.
Who was in the study: 43 patients, average age 57, most with intermediate‑risk disease and low‑blast MDS (<5%). All had platelet counts ≤30×10⁹/L at the start. Prior studies with other platelet-stimulating agents in MDS patients have been complicated by worsening blast counts.
Results: About 42% of patients had a platelet response, including 7% with complete responses. Nearly 28% reached platelet counts above 50×10⁹/L. Responses usually appeared within 7 weeks.
Predictors: Response did not depend on age, gender, risk category, MDS subtype, performance status, or gene mutations.
Safety: Side effects occurred in 30% of patients, mostly infections. Serious infections happened in about 9%, but no treatment‑related deaths were reported.
Conclusion: Hetrombopag safely raised platelet counts in LR‑MDS patients with thrombocytopenia, showing promise as a new treatment option.

High Risk MDS

What’s being studied: The VERONA trial (NCT04401748) tested venetoclax plus azacitidine (Ven+Aza) against placebo plus azacitidine (Pbo+Aza) in patients with high‑risk MDS who had never been treated before.
Who was in the study: 509 patients took part, most in their early 70s. Both groups had similar disease risks and gene mutations. Patients had an IPSS-R score >3 (intermediate, high or very high risk).
Results: Overall survival was about the same between Ven+Aza and Pbo+Aza (around 22 months). However, Ven+Aza led to more overall responses (76% vs 58%) and fewer patients progressed to AML (15% vs 20%).
Subgroups: Younger patients, those with more blasts in their bone marrow, and patients with certain gene mutations (like TP53, ASXL1, RUNX1) showed trends of better response with Ven+Aza.
Treatment outcomes: More patients on Ven+Aza achieved marrow remission with blood count improvement compared to Pbo+Aza (27% vs 18%).
Conclusion: While Ven+Aza did not improve survival compared to Pbo+Aza, it gave higher response rates and signs of benefit in some patient groups, supporting further study in high‑risk MDS.

Abstract 236 Zeiden A, et al: Efficacy, molecular and translational analysis of TP53-mutated HR-MDS with bexmarilimab and azacitidine: Updated results from the Bexmab Phase 1/2 study

What’s being studied: Bexmarilimab is an experimental medicine that helps the immune system fight MDS. It is a novel macrophage checkpoint inhibitor targeting Clever-1, a scavenger receptor expressed on malignant blasts and monocytes. It was tested with azacitidine in patients with high‑risk MDS, especially those with TP53 mutations (a gene change linked to poor outcomes).
Who was in the study: 53 high risk MDS patients (IPSS-R >3 score) joined—21 had never been treated before, and 32 had already tried hypomethylating agents (HMAs; such as azacytidine and decitabine) but their disease came back or didn’t respond.
Results in untreated patients: Response rates were high—78% in patients with TP53 mutations and 91% in those without. About half of patients with TP53 mutations had complete responses.
Results in relapsed/refractory patients: Responses were lower—46% in TP53‑mutated patients and 74% in those without. Median survival was about 13 months overall, but shorter (9 months) in the TP53‑mutated group.
Immune effects: Lab studies showed stronger immune activity in the bone marrow, with more “killer” T cells and better antigen presentation after treatment.
Conclusion: Bexmarilimab plus azacitidine looks promising for patients with TP53‑mutated high‑risk MDS, a group with very limited options.

What’s being studied: Doctors tested a new combination of oral decitabine/cedazuridine (DEC‑C; INQOVI) with venetoclax (Ven) in patients with high‑risk MDS or CMML who had not been treated before (NCT04655755).
Who was in the study: 69 patients took part, most in their 70s. Patients had MDS with excess blasts or CMML. Many had gene changes linked to poor outcomes, including TP53 and ASXL1 mutations.
Results: The overall response rate was very high—91% by older criteria and 81% by newer criteria. Nearly half of patients achieved complete remission, often after just 1–3 treatment cycles.
Safety: Side effects included low blood counts (expected with this drug combination). Some patients needed dose reductions, and a few died from infections or other complications.
Transplant outcomes: Over half of patients (55%) went on to stem cell transplant, with many showing strong responses before transplant.
Survival: Median overall survival was 30 months, with about 55% of patients alive at 2 years. Patients with ASXL1 mutations lived longer, while those with TP53 mutations had shorter survival.

Abstract 238 Borate U, et al: Phase II study of clinical efficacy of venetoclax in combination with azacitidine in patients with therapy related myelodysplastic syndrome (t-MDS)

What’s being studied: Azacitidine plus venetoclax (Aza/Ven) was tested in patients with therapy‑related MDS, a very aggressive type of MDS that often has TP53 mutations and poor outcomes (NCT05379166).
Who was in the study: 23 patients were analyzed so far. Most were men, average age 67. Over 80% had TP53 mutations and/or complex genetic changes, making them very high‑risk. The IPSS-R scores were very high (>3.5)
Results: About 57% of patients responded to treatment, including 22% who achieved complete remission. Responses lasted a median of 12.7 months. Half of patients showed blood count improvements.
Disease outcomes: 39% of patients progressed to AML. Median survival was 10 months overall, but longer (about 15 months) in responders. About 30% of patients went on to stem cell transplant.
Safety: Almost all patients had serious side effects, mostly low blood counts leading to infections like sepsis or fever. Only one patient stopped treatment because of side effects.
Conclusion: Aza/Ven showed promising activity in this very high‑risk group, especially as a possible bridge to transplant, even though survival remains limited.

What’s being studied: Doctors looked at how azacitidine or decitabine (HMAs) combined with venetoclax (VEN) worked in real‑world patients with high‑risk MDS, compared to HMA alone.
Who was in the study: 1,198 patients from 19 US academic centers. About 313 got HMA‑VEN, and 885 got HMA alone. Many had very‑high‑risk disease, therapy‑related MDS, or TP53 mutations. 75% had MDS with excess blasts. The study was retrospective and non-randomized, representing the doctor's choice in treatments (and thus may have biases).
Results: Response rates were much higher with HMA‑VEN (81% vs 39%). Complete remission was also better (17% vs 10%).
Survival: Patients on HMA‑VEN lived longer (median 22 months vs 18 months) and had fewer events like progression or death. Benefits were strongest in patients who later had a stem cell transplant, those with 10–19% blasts, de novo MDS, and those without TP53 mutations.
Genetics: The survival benefit of HMA‑VEN was also seen in patients with ASXL1 mutations, but not in those with TP53 mutations.
Conclusion: In real‑world practice (in contrast to the randomized Verona trial), HMA‑VEN improved outcomes for certain groups of high‑risk MDS patients.

Abstract 240 Braish J, et al: Durability of complete response outperforms complete response rates as a surrogate endpoint for advancing to phase III trials in high-risk myelodysplastic syndromes

What’s being studied: Doctors wanted to see if a durable complete response (lasting more than 6 months) is a better measure of benefit in high‑risk MDS than just achieving CR. Finding a good surrogate (early) endpoint is important for drug development, rather than waiting for survival results.
Who was in the study: 980 patients treated with hypomethylating agents (HMAs) at Moffitt Cancer Center. Median age was 72, and many had therapy‑related MDS.
Results: Patients who achieved CR lived longer (24 months vs 13 months for others). But only those with durable CR had a clear survival benefit. Short CRs (≤6 months) did not improve survival.
Treatment groups: CR rates were 12% with HMA alone, 12% with HMA+venetoclax, and 29% with HMA+novel agents. Durable CR occurred in about 10% of HMA patients, 9% of HMA+Ven patients, and 24% of those on novel agents.
Genetics: In patients with TP53 mutations, durable CR reduced risk of death by 38% with HMA alone, and by 73% when combined with eprenetapopt.
Conclusion: Only durable CR (lasting >6 months) truly improves survival in high‑risk MDS. This makes durable CR a more meaningful goal for new drug development than CR alone.

What’s being studied: ASTX030 is an experimental oral version of azacitidine (Vidaza) combined with cedazuridine. It aims to replace injections and reduce clinic visits for patients with MDS, CMML, or AML.
Who was in the study: 30 patients, average age 74, were treated. Most had MDS, with a few having CMML, AML, or MDS/MPN. (NCT04256317)
Results: Drug exposure with oral ASTX030 was similar to injected azacitidine overall, though body size affected levels. In MDS patients, 50% responded, with 23% achieving complete remission. About 31% of transfusion‑dependent patients became transfusion‑independent for at least 56 days.
Biology: DNA demethylation (a marker of drug activity) was comparable between oral and injected forms.
Safety: Side effects were common but mostly manageable. Nausea, constipation, and fatigue were frequent. Serious low blood counts (platelets, neutrophils, anemia) occurred in about one‑third to half of patients.
Conclusion: Oral ASTX030 worked similarly to injected azacitidine, with manageable safety. Adjusting doses by body size may improve consistency. A larger phase 3 trial (AZTOUND) is now recruiting.

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