Key Highlights from EHA 2025: Advances in MDS Diagnosis, Treatment, and Transplantation

The European Hematology Association (EHA) held their annual scientific conference in Milan Italy from June 12-15, 2025. Over 100 research studies on MDS were presented. Below is a summary of some important trials:

DIAGNOSIS and RISK STRATIFICATION

(Abstract S331) Asti G, et al. A FINE-TUNED FOUNDATION MODEL FOR DIGITAL PATHOLOGY IN MYELODYSPLASTIC SYNDROMES: ADVANCING PERSONALIZED MEDICINE

The diagnosis of MDS is made by careful examination of bone marrow under the microscope in conjunction with genetic studies.
Artificial Intelligence (AI) might improve the analysis of biopsy specimens.
Scientists used an AI computer program to evaluate bone marrow samples from 624 MDS patients.
The computer diagnosed MDS more accurately and predicted patient outcomes better.
The AI model correctly assigned World Health Organization (WHO) 2022 classification diagnosis labels in 86% of cases and improved predictive accuracy for overall survival (OS) and leukemia-free survival (LFS) with a concordance index of 0.82 for OS and 0.80 for LFS.

(Abstract PS1632) Bazinet A, et al. UPSTAGED RISK FROM THE REVISED TO THE MOLECULAR INTERNATIONAL PROGNOSTIC SCORING SYSTEM PREDICTS ADVERSE OUTCOMES IN MYELODYSPLASTIC SYNDROMES

Risk stratification is used to guide therapy decisions.
The most common systems are the IPSS-R and the newer molecular based IPSS-M
It is unknown how MDS patients fare if their risk scores differ between these two systems.
Of 1,838 MDS patients reviewed, 9% had their risk scores worsen (upstaged) and 6% had their risk scores improved (downstaged) when comparing the two risk systems.
Patients who were upstaged using the newer IPSS-M system had worse outcomes than predicted by the IPSS-R system and thus should be treated as high risk rather than low risk.
Know your risk score - calculators for these systems are available on the MDS Foundation website at https://www.mds-foundation.org/professional/resources/prognosis-calculators/https://www.mds-foundation.org/professional/resources/prognosis-calculators/.

(Abstract PS1618) Chien K, et al. RISK STRATIFICATION IN HYPOMETHYLATING AGENT-TREATED PATIENTS WITH MYELODYSPLASTIC SYNDROMES: A MULTIVARIATE MODEL (MDS-HOPE)

Risk stratification is used to guide treatment selection for patients with newly diagnosed MDS patients.
Current systems (IPSS-R and IPSS-M) have not been validated among patients who are already receiving HMA therapies (such as azacytidine or decitabine).
A review of 1,838 patients treated with HMAs was conducted.
The IPSS-M did not provide additional prognostic power over the IPSS-R (concordance indices remaining below 0.7).
Scientists developed a new scoring system called MDS-HOPE.
The new MDS-HOPE system was more accurate in predicting survival and relapse compared to older systems, helping doctors make better treatment decisions.
This new risk system will need further validation before its general usage.

LOW RISK MDS and ANEMIA

(Abstract PF634) Della Porta MG, et al. PRELIMINARY EFFICACY AND SAFETY ANALYSIS OF THE MAXILUS STUDY OF LUSPATERCEPT (LUSPA) INITIATED AT THE MAXIMUM APPROVED DOSE IN TRANSFUSION-DEPENDENT (TD) LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS)

Luspatercept is an FDA approved for the treatment of MDS related anemia (low red blood cell counts)
In prior research studies (COMMANDS and MEDALIST) luspatercept was started at a lower dose and increased as tolerated.
In this study (MAXILUS) low risk MDS participants were started at the maximum FDA approved dose rather than titrated upwards.
90 ESA naïve (no prior Procrit or Aranesp) and 50 ESA refractory/relapsed MDS patients have been enrolled thus far in this ongoing trial.
76% of ESA naïve and 67% of ESA refractory/relapse MDS patients became transfusion independent for more than 8 weeks.
The higher starting dose was well tolerated with less than 3% needing to discontinue or lower their dose.
The preliminary results from this ongoing study suggest that starting the medication at full dose, rather than titrating upwards, is possible.

(Abstract PS1640) Komrokji RS, et al. OUTCOMES WITH IMETELSTAT BY SERUM ERYTHROPOIETIN LEVELS IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO WERE TREATMENT NAIVE OR WHO HAD PRIOR TREATMENT WITH ERYTHROPOIESIS-STIMULATING AGENTS

Imetelstat is FDA approved for the treatment of anemia in low risk MDS patients requiring frequent blood transfusions who are not responding to ESAs
Patients with very high erythropoietin levels are unlikely to respond to ESAs and are also candidates for imetelstat
Researchers reviewed results from the IMerge trial to assess the impact of the baseline erythropoietin levels on the chance of having a response.
Overall, imetelstat helped 69% of the low-risk MDS patients improve their red cell blood count, with about half becoming independent of transfusions for more than 8 weeks.
Responses were seen even in MDS patients with high baseline erythropoietin levels.
The study further supports the use of Imetelstat as a front-line therapy among MDS patients with high erythropoietin levels and among low-risk MDS patients who progress on ESAs regardless of erythropoietin levels.

(Abstract PS1639) Campelo MD, et al. HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH IMETELSTAT IN THE IMERGE TRIAL

Imetelstat has been shown to improve red blood cell counts and reduce the need for transfusions among low-risk MDS patients.
This study sought to evaluate the effect of this medicine on overall quality of life.
Participants completed surveys about their health status.
MDS patients treated with imtelestat reported improvements in their quality of life compared to patients treated with a placebo.
Improvements were reported in both physical and emotional senses of well-being.
This is an important finding as it demonstrates that imetelstat treatment yields a true quality benefit and not just an improvement in a laboratory test value (rise in hemoglobin level).

(Abstract PS1628) Meuiner M, et al. A PHASE 2 PROSPECTIVE STUDY EVALUATING LOW-DOSE DEFERASIROX IN PATIENTS WITH LOW-RISK MYELODYSPLASTIC SYNDROME RESISTANT OR RELAPSING AFTER ERYTHROPOIETIN STIMULATING AGENTS (LODEFI)

Improving red cell blood counts (anemia) is a major goal in low risk MDS treatment.
Erythropoietin stimulating agents (ESAs such as Procrit and Aranesp) are commonly utilized.
Deferasirox is FDA approved to treat iron overload from multiple transfusions in low risk MDS patients, but laboratory studies have suggested that it might also improve anemia.
The investigators gave low dose deferasirox to non-transfusion dependent MDS patients who were not responding to ESAs
Nearly half of deferasirox treated MDS patients were transfusion independent at 1-year.
Larger studies are needed to confirm if low-dose deferasirox can be helpful in improving anemia.

(Abstract PF635) Valcarcel D, et al. HEMATOLOGIC IMPROVEMENT AND FATIGUE REDUCTION WITH ELRITERCEPT IN PARTICIPANTS WITH LOWER-RISK (LR) MYELODYSPLASTIC NEOPLASMS (MDS) WITH NON-TRANSFUSION DEPENDENT ANEMIA: RESULTS FROM AN ONGOING PHASE 2 TRIAL

Elritercept is an experimental medication for MDS related anemia (low red blood cell counts)
Although most MDS patients develop anemia, investigators hope that earlier treatment before transfusion dependency occurs will improve prognosis and quality of life.
Among 15 MDS patients who were not yet receiving transfusions, 13 (87%) experienced improved blood counts and 73% maintained hemoglobin levels above 11 g/dl for at least 8 weeks.
The study is ongoing, but these are encouraging preliminary results for MDS patients who are treated early in their disease course.

(Abstract PF644) Giagounidis A, et al. IMPROVEMENTS IN HEMATOLOGICAL PARAMETERS AND QUALITY OF LIFE (QOL) WITH ELRITERCEPT: RESULTS FROM AN ONGOING PHASE 2 TRIAL IN PARTICIPANTS WITH LOWER-RISK (LR) MYELODYSPLASTIC NEOPLASMS (MDS)

Elritercept is an investigational medication that has shown promise in improving red cell counts and reducing transfusion needs in low risk MDS patients.
In an ongoing study, participants who were responding to the medication with better blood counts were asked to rate their overall quality of health.
Meaningful improvements in general health quality, mostly driven by less fatigue (both experience and impact), were reported by the participants.
Results from the full trial are awaited.

(Abstract PF629) Bouligny TI, et al. A RANDOMIZED, MULTICENTER PHASE II TRIAL OF 3-DAY DECITABINE, 3-DAY AZACITIDINE, OR 5-DAY AZACITIDINE IN LOWER-RISK MYELODYSPLASTIC SYNDROME

Hypomethylating agents (HMAs including azacitidine and decitabine) are the standard initial treatment for high risk MDS.
Attenuated duration HMA regimens (such as 3 days instead of the typical 5–7-day regimens) have been advocated for low risk MDS.
In this study of 241 lower-risk MDS patients, 3 different dosing schedules were compared in cohorts of transfusion dependent and transfusion independent patients.
The overall response rate (ORR) among transfusion dependent patients was 55% for DAC3, 57% for AZA3, and 48% for AZA5 (no statistical difference)
In a statistical model that accounted for various patient factors, the was no overall survival difference between AZA3 and AZA5, but AZA5 was better than DAC3.
The overall response rate among transfusion independent patients was 47% for DAC3, 56% for AZA3, 70% for AZA5 (no statistical differences) but all were better than supportive care (no medications yielding 17% responses)
In the statistical model, there was no difference in overall survival between AZA3 and AZA5, but the survival with AZA5 was better than DAC3 in transfusion independent patients.
Thus, this study demonstrated that Azacitidine 75 mg/m2 for 5 days improved event free survival compared to 3-day azacitidine in transfusion-independent patients and improved overall survival compared to 3-day decitabine in transfusion-dependent and transfusion-independent patients with lower-risk MDS. This may be a practice changing finding.

HIGH RISK MDS

(Abstract PF626) Zhou X, et al. DECITABINE PLUS ALL-TRANS RETINOIC ACID VERSUS DECITABINE MONOTHERAPY FOR MYELODYSPLASTIC SYNDROMES WITH EXCESS BLASTS: A MULTICENTRE, RANDOMIZED CONTROLLED TRIAL

All-trans retinoic acid (ATRA) is an approved treatment for certain types of acute myeloid leukemia but has not been fully explored in high risk MDS.
227 patients with MDS who had excess blasts were given either decitabine alone or the combination of decitabine with ATRA.
Treatment with the combination resulted in higher response rates (78% vs 51%)
Treatment with the combination resulted in longer remissions (14.9 months vs 10.5 months)
However, overall survival rates and transformation to AML rates were similar between treatments.

(Abstract PS1619) Ma L, et al. SAFETY AND EFFICACY OF AZACITIDINE SEQUENTIAL SELINEXOR IN NEWLY DIAGNOSED PATIENTS WITH MYELODYSPLASTIC SYNDROMES EB1 OR EB2: A SINGLE-CENTER, SINGLE-ARM, PHASE IB/II TRIAL

Selinexor is an oral medication currently approved for the treatment of multiple myeloma.
Azacitidine is a common medication used as initial treatment for high-risk MDS (patients having blasts), but results among individuals with TP53 mutations and multiple chromosomal changes are poor.
Investigators combined these treatments in an early phase trial enrolling 33 patients.
Encouraging remission rates were noted in these higher risk patients.
94% of patients responded, including 37% complete responses.
5 of the 11 patients with TP53 mutations had a complete response, with a median overall survival of 11 months (longer than expected)
6 of the 10 patients with complex karyotype had a complete cytogenetic response.
More studies are warranted with this combination.

(Abstract PF643) Guerra V et al. CPX-351 FOR TRANSPLANT ELIGIBLE, HIGHER RISK PATIENTS WITH MYELODYSPLASTIC SYNDROMES: MOLECULAR RESPONSES AND LONG-TERM FOLLOW-UP

CPX-351 (daunorubicin and cytarabine liposome) is an FDA approved aggressive chemotherapy approved for treatment of adults with AML that has background MDS changes.
This study involved 20 transplant eligible patients with high-risk MDS.
CPX-351 given prior to the transplant resulted in an 80% remission rate.
24% were able to achieve Minimal Residual Disease (MRD) negative status (cleared all evidence of disease) with this initial therapy.
Following the transplant, 6 of 10 patients assessed became MRD negative.
The median survival for the entire cohort was almost 4 years.
CPX-351 therapy prior to transplant may be an aggressive strategy to decrease disease burden and thus improve the chance of a successful transplant.

TRANSPLANTATION

(Abstract PF1065) Yu W, et al. A NOVEL REDUCED TOXICITY CONDITIONING REGIMEN FOR OLDER MYELODYSPLASTIC NEOPLASMS PATIENTS UNDERGOING HAPLOIDENTICAL STEM CELL TRANSPLANTATION: A PROSPECTIVE COHORT STUDY

Researchers evaluated a new, less toxic chemotherapy regimen for 68 older patients (age >50 years) with MDS undergoing stem cell transplants (busulfan, fludarabine, cyclophosphamide, and antithymocyte globulin).
They found that this chemotherapy regimen was safer and just as effective as traditional treatments used in younger patients.
The new regimen helped reduce complications and improved survival rates for older patients.
This study again demonstrates that carefully selected “older” “fit” MDS patients can be considered for curative transplantation.

(Abstract PF1058) Lyu ZS, et al. THE IMPACT OF BLAST PERCENTAGE ON POST-TRANSPLANT OUTCOMES OF PATIENTS WITH MYELODYSPLASTIC SYNDROMES: A RETROSPECTIVE ANALYSIS WITHIN THE IPSS-M FRAMEWORK

Scientists studied how the percentage of abnormal cells (blasts) in the bone marrow pre-transplant affected outcomes for 225 MDS patients after a stem cell transplant.
They found that patients entering the transplant with fewer blasts had lower relapse rates.
The relapse rate was 0% for the low-blast group and 13% for the increased-blast group.
Combining the blast percentage with genetic information (from the IPSS-M) helped doctors further improve the prediction of patient outcomes.
This study suggests that “debulking” of blasts prior to transplant may be important.

(Abstract PF649) Desai SR, et al. ROLE OF PRE-TRANSPLANT MOLECULAR REMISSION ON OUTCOMES OF ALLOGENEIC STEM CELL TRANSPLANT IN MYELODYSPLASTIC SYNDROMES

Although stem cell transplantation may be curative in MDS, relapse remains a common challenge (occurring in up to 60%)
Small amounts of cancer cells remaining in the bone marrow (known as Minimal Residual Disease- MRD) may cause these relapses.
Modern gene sequencing techniques can identify MRD.
This study of 156 MDS patients undergoing transplantation found that the 2-year cumulative incidence of relapse was 30% for patients still with MRD, but only 10% lacking this small amount of disease.
The aggressiveness of the transplant regimen did not affect outcomes.
Novel approaches to reducing post-transplant relapses are needed, especially among patients who still have MRD prior to transplant.
The study also questions whether additional treatments before transplant should be considered to maximize the effectiveness of the transplant.

(Abstract PS2087) Zucenka A, et al. SEQUENTIAL ALLOGENEIC STEM CELL TRANSPLANTATION FOR VENETOCLAX-EXPOSED RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME WITH INCREASED BLASTS-2

MDS and leukemia patients often receive venetoclax as part of their initial or second-line treatments.
Unfortunately, patients who relapse after venetoclax based therapy have a poor prognosis (survival typically measured in only a few months).
Researchers tested a new aggressive treatment approach in 25 patients.
Patients received one of three different 10-day combinations of aggressive chemotherapy.
All patients then proceeded to transplantation which included additional conditioning chemotherapy.
Almost all entered remission with this dual therapy and about half survived a year.
For “fit” patients who relapse following MDS treatments, transplant options should be explored.

(Abstract S268) Malagola M, et al. IMPACT OF HYPOMETHYLATING AGENTS +/- VENETOCLAX FOR THE MANAGEMENT OF ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC PATIENTS RELAPSING AFTER ALLOGENEIC STEM CELL TRANSPLANTATION: A SUBANALYSIS ON 308 PATIENTS OF THE GITMO AML/MDS-RELAPSE REGISTRY STUDY.

Although transplantation can be curative in MDS, relapses can occur following transplantation. New treatment approaches for these later relapses are needed.
Hypomethylating agents (HMAs such as azacitidine or decitabine) with or without venetoclax were given to 308 patients with leukemia and MDS who relapsed after a stem cell transplant.
Patients with lower disease burdens at relapse (such as fewer blasts) and those who received donor lymphocyte infusions in combination with HMAs +/- venetoclax had better survival rates.
The study highlights the importance of identifying post-transplant relapses early when the MDS disease burden may be low so that effective salvage therapies can be started.

CHILDHOOD MDS

(Abstract PF638) Yi ES, et al. CLINICAL CHARACTERISTICS AND LONG-TERM TREATMENT OUTCOME IN CHILDHOOD MYELODYSPLASTIC NEOPLASM: A NATIONWIDE POPULATION-BASED STUDY IN KOREA

Researchers analyzed nationwide population data on 489 childhood MDS patients in Korea between 2003 – 2021 to understand the incidence, risk factors, and treatment outcomes.
The average age at diagnosis was 9.6 years with a slight male preponderance.
The annual incidence of MDS was 2.4 cases per million children.
44% underwent transplantation as treatment.
Busulfan based transplants and non-cord blood transplants fared better.
The estimated 5-year OS rates were 72% for patients who underwent transplantation and 80% for those who did not require transplantation.

(Abstract PF677) Vasileva M, et al. INHERITED BONE MARROW FAILURE DUE TO GATA2 GENE MUTATION WITH A PREDISPOSITION TO MYELODYSPLASTIC SYNDROMES/ACUTE MYELOID LEUKEMIA

Researchers studied 13 patients with a genetic mutation in the GATA2 gene.
These mutations can lead to bone marrow failure and increase the risk of developing MDS or acute myeloid leukemia (AML).
Mutations in exon 5 (a particular region of the GATA2 gene) were identified in 10 patients.
The median age at the time of diagnosis was 10.7 years with low blood counts as the initial finding.
This research into the molecular pathways affected by GATA2 mutations may shed light on novel therapeutic approaches that could benefit affected patients and inform risk-reduction strategies within high-risk families.

(Abstract PF520) Baccelli F, et al. VENETOCLAX AND AZACYTIDINE IN CHILDHOOD MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA: THE AIEOP EXPERIENCE

The combination of azacytidine and venetoclax has been used in adults with AML and high risk MDS (with blasts).
However, little is known about this combination in children.
33 children (aged 20 or less) with relapsed/refractory AML or high risk MDS were given the combination.
55% achieved a complete remission and 21% had a partial response with the combination.
70% of the children proceeded with transplantation; with 74% in remission a year later (possibly cured).
Additional studies with this combination in pediatric MDS are warranted.

To find out more about clinical research trials that might be helpful to you, check out the MDS Foundation Clinical Trial Matching Tool at https://www.mds-foundation.org/learn/find-a-trial/

To learn more about how clinical trials work, check out the video https://www.youandmds.com/en-mds/view/m211-a10-understanding-clinical-trials-in-myelodysplastic-syndromes-mds-animation. .

Join the Fight Against MDS