Hematologists Highlight Notable Insights From the 2025 EHA Congress

Paolo Ghia, MD, PhD

The 2025 EHA Congress was filled with practice-informing data from across hematologic oncology subsets, ranging from studies on the brink of changing treatment standards to intriguing early-phase developments. During the meeting, experts provided OncLive® with their top takeaways.

“In the field of chronic lymphocytic leukemia [CLL], there are several studies that are showing how we improve every year in the treatment of our patients,” Paolo Ghia, MD, PhD, of the Università Vita Salute San Raffaele in Milan, Italy, said of the CLL treatment paradigm during an interview at the meeting. “The thing I was most excited for was the BTK degraders. This is the next generation of treatments for patients with CLL. There are now studies in the phase 1 [setting], of course, but these molecules are moving quickly into combinations in phase 2 and phase 3 studies, where we will obtain responses even in patients who are not only double refractory—refractory to BTK inhibitors and venetoclax [Venclexta]—but also triple refractory—relapsing after [treatment with] the noncovalent BTK inhibitor pirtobrutinib [Jaypirca], which is a new therapy for our patients in the relapsed/refractory setting. BTK degraders can help us add an extra option for our patients.”

“The phase 1/2 KOMET-001 study [NCT04067336]…was interesting,” Amir Fathi, MD, of Massachusetts General Hospital in Boston, explained in an overview of notable acute myeloid leukemia (AML) research. “We also presented data on the combination of ziftomenib [KO-539] plus standard chemotherapy. Data with enzomenib [DSP-5336]—another menin inhibitor—were presented. [Findings with] the combination of oral decitabine with venetoclax were also presented at the meeting. These data are all important and will hopefully move the field forward for both upfront patients, as well as relapsed/refractory patients with AML.”

Read on to learn more about specific studies that drew a crowd!

Abstract S205: Minimal residual disease-driven strategy following isatuximab-carfilzomib-lenalidomide-dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma: primary endpoints of the phase 3 MIDAS trial

“The [phase 3] MIDAS trial [NCT04934475] was one of the French studies that was looking at a 4-drug induction [regimen of] isatuximab-irfc [Sarclisa], carfilzomib [Kyprolis], lenalidomide [Revlimid], and dexamethasone [Isa-KRd],” stated Rakesh Popat, BSc, MBBS, MRCP, RCDPath, PhD, of University College London Hospitals in the United Kingdom. “Patients were stratified thereafter according to their minimal residual disease [MRD] status. Patients who were MRD negative went down a certain pathway, and patients who were MRD positive went down an alternative pathway. The induction strategy with Isa-KRd was extremely potent, with high levels of MRD negativity. This study suggested that there is no need for tandem stem cell transplantation in patients who are MRD positive following induction because single transplant was equally as effective. The other point, for which I think we need longer follow-up, was that the study demonstrated equivalent MRD-negativity rates for patients who had continuous therapy vs patients who had a single stem cell transplant. However, we need the progression-free survival data to tease that out a bit further.”

Abstract LB4002: INCA33989 is a novel, first in class, mutant calreticulin-specific monoclonal antibody that demonstrates safety and efficacy in patients with essential thrombocythemia (ET)

“I was excited about the late-breaking abstract that was presented on the calreticulin-specific monoclonal antibody to treat patients with calreticulin-positive ET and myelofibrosis,” said Marina Kremyanskaya, MD, PhD, of the Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital in New York, New York. “It’s a completely new approach to [managing] myeloproliferative neoplasms [MPNs]. In a lot of hematology oncology, immunotherapy drugs are being used, but we haven’t seen a lot of that in [MPNs]. In this disease, we have many drugs that help patients, but we don’t have any that significantly affect the overall course of the disease. This drug has the potential to change the natural history of the disease, and that makes it exciting.”

“One of the novelties in the management of MPNs is immunotherapy,” Francesca Palandri, MD, PhD, of the University of Bologna in Italy, added in another interview. “I’m hopeful that this new and promising way of addressing the disease could bring further therapeutic opportunities and improve outcomes for our patients.”

Abstract S101: Polatuzumab vedotin, rituximab, gemcitabine and oxaliplatin (POLA-R-GemOx) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): results from the randomized phase III POLARGO trial

“Apart from CAR T-cell therapy and bispecific T-cell engagers, all the other salvage therapies for relapsed/refractory LBCL are still older and suboptimal,” said Matthew Ku, MBBS, FRACP, RACP, FRCPA/RCPA, PhD, of St Vincent’s Hospital in Fitzroy, Australia. “To see a chemotherapy backbone like rituximab [Rituxan] plus GemOx [R-GemOx] improve [with the addition] of a novel agent like polatuzumab vedotin-piiq [Polivy] is an exciting concept, especially on the back of the phase 3 STARGLO trial [NCT04408638] data, where the GemOx had glofitamab-gxbm [Columvi] added to it and showed a survival advantage [vs R-GemOx alone].”

Abstract PF924: Three-hour infusion of methotrexate at 3 G/M2 significantly reduces CNS recurrences and improves survival in large B-cell lymphomas with increased CNS risk: analysis of a single-center cohort of 501 patients

“This was a single-center [cohort] study investigating modern consensus criteria for patients at high risk of central nervous system [CNS] relapse,” Diva Baggio, MBBS, of the University College London Hospitals NHS Foundation Trust, said. “[This study included patients with] not just a CNS International Prognostic Index score of 4 or more, but also the presence of 3 or more external sites, [such as] testicular, breast, renal, or adrenal involvement. It was interesting that in the single-center study, application of end-of-treatment, high-dose methotrexate was associated with reduced CNS relapse, as well as overall event-free survival [benefit, showing that this treatment] perhaps has some systemic control, as well. This is an interesting finding because it goes against some of the [data from the] big real-world studies we’ve seen published recently that questioned the efficacy of CNS prophylaxis.”

Abstract PF936: CAR T-cell therapy is efficient in vitreoretinal lymphomas. A LOC network study

“Vitreoretinal lymphoma is a rare entity, and we still have a lack of clear therapeutic algorithms of how to treat these patients based on high-level data because it is so rare,” Baggio added. “This was an interesting, practice-informing study that showed the presence of detectable CAR T cells in the vitreoretinal space when sampled, as well as a high clinical response rate in patients who were infused with CAR T-cell products for relapsed/refractory vitreoretinal lymphoma.”