The 2025 European Hematology Association (EHA) Congress in Milan showcased groundbreaking advances in hematologic cancer treatment, with researchers presenting compelling data on novel therapeutic approaches that could transform patient outcomes across multiple blood cancers.
Trispecific Antibody Shows Promise in Multiple Myeloma
Rakesh Popat, MBBS, PhD, of University College London, presented initial phase 1 results of JNJ-5332, an investigational trispecific antibody targeting CD3, BCMA, and GPRC5D in relapsed/refractory multiple myeloma. The novel agent aims to deliver more comprehensive targeting of myeloma cells, prevent antigen escape, and increase specificity to tumor cells.
The study identified 100 mg subcutaneously every 4 weeks as the recommended phase 2 dose, with a manageable adverse effect profile. Prophylactic tocilizumab reduced the incidence and severity of cytokine release syndrome, which Popat said "underpins our ability to use this as an outpatient strategy."
Efficacy results were particularly striking: 70.4% of BCMA/GPRC5D-naïve patients receiving the recommended dose achieved at least a complete response. Popat characterized the overall response rate results as comparable to those seen with chimeric antigen receptor (CAR) T-cell therapy but with this off-the-shelf, outpatient-administered agent.
Bispecific Combination Tackles Challenging Extramedullary Disease
In the late-breaking session, Shaji Kumar, MD, of Mayo Clinic presented findings from the phase 2 RedirecTT-1 trial of talquetamab and teclistamab in patients with relapsed or refractory multiple myeloma and extramedullary disease. This patient population faces particularly poor outcomes, with an 87% lower likelihood of responding to treatment.
The combination therapy demonstrated remarkable efficacy with a 78.9% overall response rate and deep responses, with over half (54.4%) achieving at least complete response. Kumar noted a near tripling of complete response rate compared with monotherapy. The majority of responders still on therapy as of the data cutoff were switched to monthly dosing with no reduction in response.
"This regimen represents an off-the-shelf dual-targeting bispecific combination that has produced results that we had not seen previously in the context of extramedullary disease," Kumar said, describing it as "a big step forward and will hopefully change the natural history of the disease."
DLBCL Treatment Landscape Expands
Matthew Matasar, MD, of Rutgers Cancer Institute delivered results of the phase 3 POLARGO trial of polatuzumab vedotin, rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in transplant-ineligible patients who had received at least one prior line of treatment.
The trial met its primary endpoint with a stratified hazard ratio of 0.60 (95% CI, 0.43-0.83; P = .0017) for overall survival, indicating a 40% reduction in risk of death in the Pola-R-GemOx arm versus those receiving R-GemOx alone.
Matasar described the results as encouraging for showing the potential of polatuzumab vedotin in allowing patients to avoid bendamustine. "We do have a broadening armamentarium for treatment of relapsed or refractory [DLBCL], and it's good to have the tools," he concluded, adding that he sees a possible role for this regimen in helping patients bridge to CAR T therapy.
Novel Approaches for Rare Blood Disorders
Harry Gill, MD, of the University of Hong Kong, presented results from the phase 3 SURPASS-ET trial of ropeginterferon alfa-2b (ropeg) for second-line essential thrombocytopenia (ET). The trial compared ropeg against anagrelide in patients with high-risk ET who were resistant to or intolerant of hydroxyurea.
The trial met its primary endpoint of modified European LeukemiaNet response rate (42.9% for ropeg vs 6.0% for anagrelide; P = .0001). The achievement of at least partial molecular response by 30.6% of the ropeg arm and no patients in the anagrelide arm led Gill to hope that this new therapeutic option could have disease-modifying potential.
John Mascarenhas, MD, of Mount Sinai, presented findings on INCA33989, an investigational monoclonal antibody for treating essential thrombocythemia with CALR mutations. In phase 1 trials involving 49 patients, no dose-limiting toxicities were observed, and patients largely experienced rapid platelet count normalization and profound molecular responses.
Advances in Transplant Medicine
David Curtis, MBBS, PhD, of Monash University presented findings from the ALLG BM12 CAST phase 3 trial of cyclophosphamide for preventing graft-vs-host disease (GVHD) after matched sibling peripheral blood stem cell transplant. In the experimental arm, 49% of patients survived to 3 years post transplant without GVHD or relapse, whereas this rate was just 14% in the standard-of-care arm. Importantly, there was no increase in cancer recurrence seen with the investigational regimen.
Curtis expressed optimism that the new regimen could be "simple, cheap, but practice-changing," and in a press briefing said that these data could be the "nail in the coffin" for standard prophylaxis.
Molecular Insights Drive Future Therapies
According to session chair Martin Dreyling, MD, of LMU Hospital Munich, research on the molecular and genetic levels is driving advances in clinical therapy for hematologic disorders. The congress featured presentations on molecular characterization of chronic lymphocytic leukemia and machine learning approaches to AML classification that could further personalize outcome prediction.
These diverse findings reflect what one presenter called "a vibrant clinical specialty," with advances spanning from novel therapeutic combinations to molecular diagnostics that promise to transform the treatment landscape for patients with hematologic malignancies.
