Experts Underscore the Top Abstracts to Watch at the 2025 EHA Congress

Naval G. Daver, MD

The 2025 EHA Congress will spotlight some of the top data and research emerging across the hematologic oncology field. To prepare for this year’s meeting, OncLive® asked experts to outline the most anticipated data and research being presented in Milan, Italy.

Exclusive insights were gathered from:

• Naval G. Daver, MD, a professor in the Department of Leukemia of the Division of Cancer Medicine and director of the Department of Leukemia in the Division of Leukemia, Research Alliance Program, at The University of Texas MD Anderson Cancer Center in Houston
• Aaron Gerds, MD, an assistant professor in the Department of Medicine of the School of Medicine and a member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center; as well as a physician in the Department of Hematology and Medical Oncology at Cleveland Clinic in Ohio
• Tycel Phillps, MD, an associate professor in the Division of Lymphoma of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California

Check out the top abstracts our experts highlighted and their significance.

AML

Abstract S135: All-oral decitabine-cedazuridine (DEC-C) + venetoclax (VEN) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for induction chemotherapy: phase 1/2 clinical trial results

Daver: This [phase 1/2 trial (NCT04657081)] is looking at a completely oral frontline regimen for newly diagnosed, older, unfit [patients with] acute myeloid leukemia [AML]. This trial is building on the success of the intravenous [(IV) regimen] azacitidine plus venetoclax [Venclexta], which has been approved and extensively used in the United States [U.S.] and [internationally] for [patients with] frontline, older, unfit AML who cannot tolerate induction. [Azacitidine (Vidaza) plus venetoclax] has given us very good response rates, durability, and encouraging improvements in survival. Now, we’re moving those [patients to receive] a fully oral [regimen of] DEC-C and oral venetoclax, which is very convenient and nice for patients to receive as a fully oral regimen. The data show that the response rates with oral DEC-C and venetoclax are very similar to what we see with the IV formulations. There is some additional myelosuppression seen with oral DEC-C, and one has to be aware of this and do dose adjustments. However, it seems to be quite tolerable overall, and [the regimen] could emerge in the future as the [standard] oral doublet for these patients.

We are building on that doublet with the addition of targeted therapy. We have ongoing studies from MD Anderson looking at oral DEC-C with oral venetoclax, with the addition of either an IDH inhibitor for IDH-mutated [AML], a FLT3 inhibitor for FLT3-mutated [disease], or a menin inhibitor. Globally, in maybe 3 to 4 years, we may be able to give 3-drug oral regimens with [high] response rates, even for our patients above 65 or 70 years of age. This is quite amazing, because just 10 years ago for similar patients, we were giving single-agent, IV azacitidine with a response rate of approximately 20% to 25%. Now, with oral triplet combinations, we may be getting to [response rates of] 90% without an IV component. This really shows a major shift in the safety, deliverability, and efficacy of these regimens.

Abstract S149: Phase 3 study of intensive chemotherapy with or without dasatinib in patients with core-binding factor acute myeloid leukemia – final analysis of the AMLSG 21-13 trial

Daver: [This phase 3 trial (NCT02013648)] looked at intensive chemotherapy with or without dasatinib [Sprycel] in patients who have c-KIT–mutated, newly diagnosed, core-binding factor [CBF] AML. Our approach at MD Anderson, historically, has been to add gemtuzumab [Mylotarg]—a CD33-directed antibody—to the backbone of FLAG. With that, we have shown a 5-year overall survival [OS] rate close to 85%, even in adults with CBF AML. Based on these data, we will be continuing that practice and not adding dasatinib for those who have a c-KIT mutation. That should be not considered as a priority going into the future.

Abstract S137: RP2D determination of bleximenib in combination with VEN+AZA: phase 1b study in ND & R/R AML with KMT2A/NPM1 alterations

Abstract S136: Ziftomenib combined with intensive induction chemotherapy (7+3) in newly diagnosed NPM1-m or KMT2A-r acute myeloid leukemia (AML): updated phase 1a/b results from KOMET-007

Daver: Without going into too much detail, there are a number of menin inhibitor abstracts that will be presented; [some combinations have included] 3+7 with bleximenib [JNJ-75276617], as well as azacitidine and venetoclax plus bleximenib. [For bleximenib, findings from] a salvage cohort [will be presented], which were also shown [at the 2024 EHA Congress]. However, more interesting to us, there is also a frontline cohort of azacitidine and venetoclax plus bleximenib. It will be interesting to see the efficacy and the deliverability. How many days of venetoclax could be given safely? What was the dose of bleximenib? What were the count recovery [times], neutropenic fever rates, myelosuppression [rates], and times between cycles? A lot of these nuanced things that we look at when use a triplet have to be taken into account. Overall, we do believe that such a combination, even in the frontline setting, may be highly effective and potentially even curative for some of these [patients with] NPM1 [mutations] or KMT2A rearrangements.

There are also going to be data looking at the combination of azacitidine, venetoclax, and ziftomenib [KO-539], both in the relapsed and frontline [settings], as well as induction chemotherapy with ziftomenib. [These data are] going to be [too] early—given the follow-up for most of these [studies] is 6 to 10 months—to make any conclusive decisions on how these [combinations] will affect the duration of remission, transplant rates, and OS. However, we should be able to get an idea about safety, the durations of [therapy for] venetoclax and the menin inhibitor, and the doses of those drugs, as well as early efficacy in terms of remission and potentially minimal residual disease negativity, which historically has translated to survival. [These data] may give us a hint, but we do think that these are the directions that will be developed in the future with the menin inhibitors moving from salvage, single-agent use to frontline [combinations].

MPN

Aaron Gerds, MD

Abstract S223: Pelabresib in combination with ruxolitinib for Janus kinase inhibitor-naive patients with myelofibrosis: 72-week follow-up with long-term efficacy outcomes of the phase III MANIFEST-2 study

Gerds: The 72-week data for MANIFEST-2 [NCT04603495] are going to be something everybody’s looking at. We’re looking to see if is there going to be a survival advantage or something else to [point to, rather than] worrying about the TSS50. What we’ll see is potentially a better treatment durability with the combination vs ruxolitinib alone. The OS [curves] probably won't be splitting at that point yet; it’s probably still too early, but those are going to be the kind of things that we could potentially see in the 72-week data at EHA.

Abstract PF856: A phase 1b/2 study of DISC-0974, an anti-hemojuvelin antibody, in patients with myelofibrosis and anemia

Abstract PF1845: DISC-0974 (an anti-hemojuvelin antibody) in non-transfusion-dependent patients with myelofibrosis: laboratory correlates of major anemia response

Gerds: DISC-0974 is a monoclonal antibody that lowers hepcidin levels. It seems to do a better and more consistent job at lowering hepcidin levels than pacritinib [Vonjo] or momelotinib [Ojjaara], and we see a fair number of anemia responses there, even in heavily transfused patients.

MCL

Tycel Phillips, MD

Abstract S237: Combination treatment with novel BCL2 inhibitor sonrotoclax (BGB-11417) and zanubrutinib induces high rate of complete remission for patients with relapsed/refractory mantle cell lymphoma

Phillips: They’ll have a presentation looking at sonrotoclax, which is a new BCL-2 inhibitor. [The phase 1 BGB-11417-101 trial (NCT04277637)] is looking at the combination [of sonrotoclax] with zanubrutinib [Brukinsa] in patients with relapsed/refractory MCL. This is their version of the [regimen from the phase 3] SYMPATICO trial [(NCT03112174), which evaluated ibrutinib (Imbruvica) plus venetoclax]. This presentation will be fairly interesting.

Abstract S233: Efficacy of rituximab-bendamustine with or without acalabrutinib in patients with untreated, high-risk mantle cell lymphoma: an analysis of the phase 3 ECHO trial

Phillips: [Martin Dreyling, MD, of LMU Hospital Munich in Germany, and colleagues] are presenting results comparing outcomes of bendamustine plus rituximab [BR] with or without acalabrutinib [Calquence] in [patients with] untreated, high-risk MCL. This presentation looks like a subset analysis on the phase 3 ECHO study [NCT02972840], which led to the approval of BR plus acalabrutinib [for patients with previously untreated MCL] in the U.S.1

BPDCN

Abstract S141: Efficacy and safety of pivekimab sunirine (PVEK) in patients (Pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study

Daver: One [abstract] that we’re very excited about is [about] a new drug called pivekimab sunirine [IMGN632]. This is being developed in both blastic plasmacytoid dendritic cell neoplasm [BPDCN] and AML. The data are being presented at EHA, [and they were] also presented at the 2025 ASCO Annual Meeting. [Data have shown] that in frontline BPDCN, this drug has high response rates with a very good safety profile. It can be delivered as an outpatient [therapy], and we’re seeing that more than 50% of patients are able to transition to transplant; therefore, the drug does not seem to add too much toxicity, allowing patients to safely achieve a remission and then move on toward the more curative-intent treatment with the stem cell transplant.

[Pivekimab sunirine] looks like it could be emerging as a new frontline standard for BPDCN, based on the data being presented here. The things we like with this agent compared with the other existing drugs, such as tagraxofusp-erzs [Elzonris], are that [pivekimab sunirine] is associated with very minimal capillary leak syndrome. It is administered every 21 days, so it’s easier [to administer] than [agents that are given] 3 to 5 days in a row, and it is predominantly outpatient. Since there is very minimal or low capillary leak syndrome, we do not have to do very vigilant albumin level monitoring, weight monitoring, and fluid monitoring. [Pivekimab sunirine] could be a very good option going into the frontline space in the future for BPDCN.

We’re also potentially going to be looking at[Pivekimab sunirine] in larger studies in AML, where there are already some data showing that it is effective as a single agent in the relapsed/refractory [setting]. However, now we’re moving it up front in combination with azacitidine and venetoclax, and that may be another strategy that is developed in the future.

Reference

FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. FDA. January 16, 2025. Accessed June 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-bendamustine-and-rituximab-previously-untreated-mantle-cell-lymphoma