Leading hematologists from Cleveland Clinic and Fred Hutchinson Cancer Center share their expert picks from ASH 2025, spotlighting practice-changing research in leukemia and myeloproliferative neoplasms (MPNs), including new data in AML, CLL, CML, MDS, and polycythemia vera that may reshape clinical decision-making.

With the conclusion of the 2025 American Society of Hematology (ASH) meeting in Florida, several innovative, practice-changing studies were unveiled, capturing the attention of leading hematologists. Based on recommendations from experts at the Cleveland Clinic and Fred Hutchinson Cancer Center, below are some of their top abstract picks presented at ASH 2025 within the leukemia and myeloproliferative neoplasm (MPN) space.

1. Management and outcomes of patients diagnosed with chronic myeloid leukemia in blast Phase: A multicenter analysis by the H Jean Khoury cure CML consortium.

Presented by Dr. Akriti Jain from Cleveland Clinic, this retrospective study looked at how people with blast phase chronic myeloid leukemia (CML-BP), the most aggressive stage of CML, are treated and how they do over time. The researchers reviewed 283 patients treated between 2010 and 2025 and found that treatment approaches were very mixed, with some patients receiving only targeted pills called tyrosine kinase inhibitors (TKIs), some receiving only chemotherapy, and most receiving a combination of both.

Patients treated with a combination of chemotherapy and a TKI lived much longer than those treated with either chemotherapy or a TKI alone, and newer TKIs, such as second-generation drugs and ponatinib, led to better responses than the older drug imatinib. Many patients (over half) were able to proceed to a stem cell transplant, and those who underwent transplant within six months of blast phase diagnosis had the best survival, although overall survival for CML-BP remained limited.

2. Results from paradigm - a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia.

In this study, Dr. Amir Fathi from Massachusetts General Hospital and colleagues from several hospitals and cancer institutes across the country asked whether a newer, less intensive drug combination could safely replace traditional “7+3” chemotherapy as the first treatment for adults with acute myeloid leukemia (AML) who are fit enough for standard chemo. This trial instead compared intensive chemotherapy to a targeted, lower-intensity regimen of azacitidine plus venetoclax (aza-ven).

The researchers enrolled 172 adults with AML and randomly assigned them to receive either aza-ven or intensive chemotherapy, then followed them to see how well the leukemia responded, how long patients stayed in remission, and how the treatment affected survival, side effects, and quality of life. Patients who received aza-ven were more likely to have their leukemia respond and reach remission, and their event-free survival (time without progression, relapse, or death) was significantly longer than with intensive chemotherapy. More patients in the aza-ven group were able to go on to stem cell transplant, early deaths were lower, and they spent less time in the hospital and ICU while reporting better quality of life, fewer symptoms, and less depression early in treatment. These findings suggest that aza-ven may not only be more effective than standard chemotherapy in this setting, but also easier on patients and their daily lives.

3. Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial

In this study, Dr. Othman Al-Sawaf from University Hospital of Cologne and colleagues from institutions across Europe compared two major modern approaches for treating previously untreated chronic lymphocytic leukemia (CLL): taking the BTK inhibitor ibrutinib continuously versus receiving time-limited “fixed-duration” combinations built around the BCL2 inhibitor venetoclax. The randomized phase 3 CLL17 trial assigned over 900 patients to one of three regimens: continuous ibrutinib alone, venetoclax plus the antibody obinutuzumab (VO) for about one year, or venetoclax plus ibrutinib (VI) for a fixed course.

After a median follow-up of just under three years, the chances of being alive without disease progression at three years (progression-free survival) were very similar across all three arms, showing that the fixed-duration VO and VI regimens were not inferior to continuous ibrutinib. Response depth favored the venetoclax-based combinations: VO and VI produced much higher rates of deep remissions with undetectable measurable residual disease than ibrutinib alone, and more complete remissions. Overall survival at three years was high and comparable in all arms. Side effects differed somewhat: infections were common in all groups, but cardiac problems and second cancers occurred more often with continuous ibrutinib, while blood and gastrointestinal side effects were more frequent with venetoclax combinations.

Taken together, these results suggest that fixed-duration venetoclax-based therapy can match continuous ibrutinib in controlling CLL while offering time-limited treatment and deeper remissions, and may become a preferred option for many patients.

4. 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)

Dr. Guillermo Garcia-Manero from MD Anderson Cancer Center, alongside researchers across institutions worldwide, investigated whether adding venetoclax to azacitidine (Ven+Aza) could improve outcomes for patients with high-risk myelodysplastic syndrome (HR-MDS), a blood disorder that often progresses to leukemia and has a poor prognosis, especially for those not eligible for stem cell transplant. In the phase 3 VERONA trial, 509 newly diagnosed patients were randomly assigned to receive either Ven+Aza or azacitidine plus placebo (Pbo+Aza), aiming to measure overall survival as the main goal while tracking responses and subgroup benefits.

The study found no overall survival difference between the arms (22 months for Ven+Aza vs 21.7 months for Pbo+Aza), but Ven+Aza led to significantly higher modified overall response rates (76% vs 58%), including more complete or marrow responses, especially in younger patients under 75, those with excess blasts, and certain mutations like ASXL1, TP53, or RUNX1. More Ven+Aza patients proceeded to transplant (17% vs 13%) with better pre-transplant responses, and fewer needed additional therapy beforehand, alongside a lower rate of transformation to acute myeloid leukemia (15% vs 20%).

These results suggest Ven+Aza offers stronger disease control and bridges more patients to transplant in select HR-MDS subgroups, despite not extending overall survival, potentially guiding personalized treatment choices for this challenging disease.

5. Venetoclax and decitabine in myeloproliferative neoplasm-blast Phase (MPN-BP): Results of enable, a gimema and airc-mynerva multicenter, Phase 2 trial

This abstract, presented by Dr. Alessandro Vannucchi from the University of Florence, Italy, highlights a new treatment option for people whose chronic blood cancer, called a myeloproliferative neoplasm (MPN), has changed into an aggressive “blast phase.” In this blast phase, the disease behaves like an acute leukemia and is often rapidly fatal, and many patients are too unwell to tolerate intensive chemotherapy or a stem cell transplant.

The ENABLE study tested a gentler combination of two drugs, venetoclax and decitabine, in 101 patients treated at many centers. The goal was to see how many people were still alive and had not had their disease get worse one year after starting treatment. About one in three patients met this goal, which is better than what is usually seen with older treatments in this setting. Nearly two-thirds of patients had their disease shrink or go into remission after two treatment cycles, and some improved enough to go on to a stem cell transplant, which can sometimes offer a chance of long-term control.

Patients who responded early, after the first treatment cycle, lived longer and had better disease control than those who did not respond. Certain genetic changes in leukemia were linked to better or worse responses, which may help doctors identify who is most likely to benefit. Side effects, such as low blood counts and infections, were common but expected for this type of treatment. Overall, this study suggests that the venetoclax–decitabine combination may offer a meaningful new option for older or frail patients with this very high-risk form of blood cancer.

6. Rusfertide or placebo plus current standard-of-care therapy for polycythemia vera: Durability of response and safety results through week 52 from the randomized controlled phase 3 VERIFY study

Dr. Andrew Kuykendall from Moffitt Cancer Center and colleagues assessed a new injectable treatment called rusfertide for people with polycythemia vera (PV), a blood cancer that often requires frequent blood draws (phlebotomies) to keep the red blood cell count under control. In this phase 3 study, patients who needed many phlebotomies despite standard treatment were randomly assigned to receive weekly rusfertide or a placebo, on top of their usual medicines, and then all patients were allowed to receive rusfertide after the first part of the trial.

The team looked at whether rusfertide could keep patients from needing further phlebotomies and maintain their hematocrit (the percentage of red blood cells in the blood) below 45%, a key treatment goal in PV. Among patients who started rusfertide from the beginning, about 6 in 10 were able to go an entire year without again meeting criteria to need a phlebotomy, and their hematocrit generally stayed below 43%. Patients who initially received a placebo and then switched to rusfertide also showed a strong benefit once they crossed over, with most no longer qualifying for phlebotomies after switching. Improvements in fatigue and PV-related symptoms were maintained over time for those on rusfertide.

Rusfertide was generally well tolerated. The most common side effects were mild to moderate reactions at the injection site, anemia, and fatigue, with serious side effects seen in a small minority of patients. Overall, these results suggest that adding weekly rusfertide to standard therapy can provide durable control of blood counts, reduce the need for phlebotomies, and help maintain symptom improvements for at least one year in patients with PV who previously required frequent blood draws.