Hematocure at the 30th European Hematology Association (EHA) Annual Congress

June 16, 2025. The 30th European Hematology Association (EHA) Annual Congress that wrapped up last weekend in Milan was the largest EHA annual meeting ever, with just over 17,000 attendees (15,000 in person in Milan). EHA received over 4,000 submissions for oral and poster presentations. On the malignant hematology front, there was a lot of excitement around innovative dual-targeting CARTs, novel trispecific T-Cell Engagers (TCEs) and small molecules inhibitors. Hematocure’s team attended the meeting and summarized some of EHA2025 most important disclosures.

Myeloid Malignancies

• EHA2025 kicked off on June 12 with an exciting session on menin inhibitors:

  • Data was presented by Andrew Wei, MBBS, PhD on the combination of bleximenib with venetoclax (ven) and azacytidine (aza) in Relapsed and Refractory (R/R) and Newly Diagnosed (ND) Acute Myeloid Leukemia (AML). Good activity and safety were seen in both the KMTA-recombinant (KMT2A-r) and NPM1-mutant (NPM1-m) groups. Low rates (4%) of Differentiation Syndrome (DS) and no QTc prolongation signal seen. At the Recommended Phase 2 Dose (RP2D) of 100mg bleximenib, the composite Complete Remission (cCR) rate was 59.1% in R/R and 75% in ND, the Overal Response Rate (ORR) was 57.1% in prior ven-exposed, 93.3% in patients with no prior ven exposure. No menin resistance mutations were observed. Bleximenib is moving rapidly through development with the cAMeLot-2 Phase 3 study initiating shortly.

    

o   On the heels of ziftomenib KOMET-001 presentation at ASCO25, Harry Erba, MD, PhD updated at EHA2025 the KOMET-007 study (ziftomenib plus 7+3 in ND AML). The combination was well tolerated with promising initial responses. Low rate of cytopenia and no additional myelosuppression were seen with the combination compared to 7+3. Only one case of DS, which was successfully managed. A cCR rate of 93% was seen in NPM1-m and 89% in KMT2A-r. cCR MRD negativity (assessed by flow cytometry) was 68% for NPM1-m (median of 4.7 weeks) and 83% for KMT2A-r (median of 4.1 w.). 96% of NPM1-m and 88% of KMT2A-r subjects remain alive and on study (median follow-up of 25 weeks and 16 weeks respect.)

o   Revumenib (Revuforj) was the first agent in this class approved last year. At this EHA2025 meeting, Joshua Zeidner, MD presented data of revumenib (revu) + aza/ven in ND older unfit as part of the Beat-AML study. The combination was feasible at both revu doses explored (113 mg or 163 mg orally every 12 hours in combination with strong cytochrome P450 inhibitor azoles). Cytopenias and delays in continuation phases cycles warranted pre-emptive dose reduction and the study was amended thereafter to ven 14 days every cycle. ORR of 88%, cCR of 81%, CR=67% with 100% flow cytometry MRD negativity seen in responding patients. The activity in higher-risk disease compared favorably to aza+ven. All patients responded and none had refractory disease after the first 1-2 cycles. The study was simultaneously published in the Journal of Clinical Oncology.  The pivotal EVOLVE-2 Phase 3 study (aza/ven/revu versus aza/ven/placebo in ND older/unfit NPM1m and KMR2Ar AML) has just been initiated.

• While next-generation targeted small molecules are the exciting newcomers for AML and MDS, standard chemotherapy still has an important role to play. Gail Roboz, MD presented the Phase 1/2 ASCERTAIN-V study of the all-oral combination of decitabine-cedaruzidine (DEC-C) plus ven in ND AML ineligible for induction chemotherapy. Good outcomes were seen, comparable to historical parenteral aza+ven with a CR rate of 46.5% and a median OS of 15.5 months. Most frequent Grade ≥ 3 AEs were as expected. This data cements ven + DEC-C as a potentially new all-oral Standard-of-Care (Soc).  

• Novel Immune approaches.

The field of CART and TCEs for myeloid malignancies is still nascent. Drs. Sarah Gorashian and Marion Subklewe reviewed recent data at EHA June 14 CART in AML session. While early small studies targeting single antigens have been mostly unsuccessful, newer approaches using innovative platforms and often multi-antigen targeting are underway. Among these are the CLEAR-AML study utilizing a CLL1 armored CART product which is ongoing at MSKCC, and the MATILDA trial that will employ a tri-antigen (CD33, CD123, CLL1) autologous CART about to open at UCL.

• High-Risk Myelodysplastic Syndrome continues to be a drug R&D challenge

At the closure of EHA2025 the news came out that the global Phase 3 VERONA trial evaluating ven in combination with aza  for ND Higher-Risk Myelodysplastic Syndrome (HR-MDS) had not met the primary endpoint of OS.  This brings the tally to 17 consecutive negative randomized HR-MDS trials and highlights the need to potentially reevaluate study designs and endpoints in this indication.

• María Queralt Salas, PhD presented the results from a prospective multicenter study that validated a new HCT frailty scale (HCT-FS) to assess frailty to allo-transplant. In this study that was conducted both in Canada and Spain, the tool provided reliable measurements of the frailty status of allo-transplant candidates that were predictive of outcomes. The test can be administered in 10 min and is applicable to both younger and older individuals.

Lymphoid Malignancies

• Large B-Cell Lymphomas (LBCLs)

o   Dual targeting of CD19 and CD20. Given loss of antigen emerging as a major mechanism of resistance to CD19- and CD20-targeted agents, developing dual CD19/CD20 targeting assets as a mean to maximize activity and counter resistance has become the new front. Here are two of the studies on that front from EHA2025:

• Among the most exciting new agents presented at EHA2025 in the field of LBCL was JNJ-90014496 (JNJ’4496), a novel dual CD19/CD20 CART explored in R/R LBCL, including DLBCL. In this first disclosure of clinical data for the ongoing Phase 1b, an ORR rate of 100% and a CR rate of 80% were seen at the RP2D. No Gr. 3/4 CRS observed to date with, and one Grade 3 ICAN in in a case of CNS lymphoma that resolved quickly. Importantly, no prophylactic treatment used for CRS and ICANS.

• KITE-363 is another CD19/CD20-targeting CART that was updated at EHA2025 by Saurabh Dahiya, MD, FACP.  In the Phase 1 study, KITE-363 showed a good safety profile and demonstrated high rates of response in highly refractory CAR-naïve LBCL. At the Dose Level 3 of 2x106 CART cells, an ORR rate of 87% and CR rate of 78% were seen, with a median duration of CR that has not been reached yet. Most interesting is the low toxicity profile seen (no Grade ≥3 CRS and ICAN, and only of short duration for lower grades) in the face of high CART expansion. Given this profile, KITE-363 is also now being developed in the treatment of autoimmune diseases.

  
  

  o   A first disclosure of the EPCORE-NHL2 study (epcoritamab + R-ICE in R/R DLBCL patients eligible for transplant) was presented by Raul Cordoba, MD, PhD. Epcoritamab (epco) + R-ICE demonstrated and ORR of 87% and CR rate of 65% in 2+ lines R/R DLBCL patients. Most patients (65%) completed epco + R-ICE and proceeded to transplant. Treatment was manageable with no discontinuation due to AEs. Only low-grade CRS events were seen, and all resolved quickly. The results continue to support that adding epco to chemoimmunotherapy increases the proportion of patients who respond to treatment and proceed to transplant.

  o   Matthew Matasar, MD reported on the Phase 3 POLARGLO (CD79b-ADC Polatuzumab vedotin + R-GemOx vs R-GemOx in R/R DLBCL). The study met its endpoint of improving OS with a 40% reduction of risk of death vs R-GemOx (OS of 19.5 months for Pola-R-GemOx versus 12.5 months for R-GemOx). ORR at EOT was 52.7% for Pola-R-GemOx versus 24.6% for R-GemOx. The benefit was seen across all risk groups (ABC and GCB). The safety profile generally favored Pola-R-GemOx, with slightly more infections (14.1% vs 8.0%) with Pola-R-GemOx (mostly COVID-19); peripheral neuropathy was more common with Pola-R-GemOx vs R-GemOx (57.0% vs 28.8%).

  
  

  

  o   Given the paucity of agents for PTCL and the dismal response rates observed with current drugs, the presentation from Yuqin Song, MD, PhD from Peking University Cancer Hospital was received with interest. In a Phase I R/R PTCL trial of SHR2554, an oral, small molecule EZH2 inhibitor, the primary endpoint was met with an ORR of 64.2%. A phase III R/R PTCL trial comparing SHR2554 to histone deacytylase inhibitor tucidinostat (the only approved agent for PTCL that has an ORR of ~25%) is currently underway.

  
  

  o   Inspired by what is happening in multiple myeloma, there is now a push to use MRD as a regulatory endpoint across various hemato-oncology indications. Martine Chamuleau, MD, PhD presented findings on the prospective validation of End-of-Treatment (EOT) ctDNA MRD by PhasED-Seq in patients with DLBCL from the HOVON-12 trial. The study included 160 subjects, and the median follow-up was 2.8 years. EOT ctDNA MRD was highly prognostic for both PFS and OS.

•  Follicular Lymphoma (FL)

o   Stefano Luminari, MD shared the 2-Year update from the Phase 2 ELM-2 study of odronextamab (odro) CD20xCD3 in R/R FL. In this longer-term follow-up, odro demonstrated deep and durable response in heavily pre-treated R/R FL with an ORR of 80%, CR rate of 74%, DOCR 32.2 of months. The median PFS is 23 months and even longer in patients who became ctDNA MRD negative at 12 weeks by Adaptive NGS. Safety was generally manageable. Multiple OLYMPIA Phase 3 randomized studies are ongoing in earlier lines with fixed treatment duration and no hospitalization required.

o   Marek Trneny, MD presented the Phase 3 inMIND study  of anti-CD19 tafasitamab + Len and rituximab in R/R FL. The study met its primary endpoint of prolonging PFS in R/R FL, with a 57% reduction in risk of progression, relapse, or death. Benefit was observed in all pre-specified subgroups including patients with POD24, refractory to prior anti-CD20 therapies, and treated with multiple prior lines. While the OS data is immature, a trend in favor of tafasitamab was observed. The safety profile is manageable. Of note, the study is one of the first to validate the approach of combining anti-CD19 and anti-CD20 monoclonal antibodies for the treatment of FL. Right after EHA2025, the FDA approved tafasitamab-cxix for R/R FL based on inMIND.

o   Catherine Thieblemont, MD, PhD shared the 4-Year update from the Phase 2 ELARA trial of CD19 CART tisagenlecleucel (Kymriah) in high-risk R/R FL. The estimated 45-month PFS was 50.2% and median OS was not reached. MRD data was evaluable for about a third of patients in whom 90% MRD negativity was achieved at any time point. Tisagenlecleucel continues to demonstrated robust durable responses at 4-year post-infusion, even in patients with higher risk features, along with a favorable safety profile.

• CLL, SLL and MCL

Multiple Bruton’s Tyrosine Kinase (BTK) inhibitors combinations with Bcl-2 inhibitors were presented at EHA2025 including:

o   The 5-Year update of the FLAIR study was presented at by Dr. Talha Munir. FLAIR is a Phase 3, multicenter, open-label trial, for previously untreated CLL requiring therapy in which subjects are randomized to receive ibrutinib + venetoclax (I+V), ibrutinib (I) alone, or FCR. The primary endpoint is undetectable MRD in bone marrow (BM) within 2 years in the I+V group as compared with the I group, and a secondary endpoint was PFS in the I+V group as compared with the FCR group.  In this updated analysis, at two years 350 patients had undetectable MRD BM: 73.1% of subjects in the I+V group as compared with none in the I group, and 60.8% in the FCR group. With a median follow-up of 62.2 months, disease progression or death occurred in 18 cases in the I+V group, as compared to 59 (I) and 112 (FCR). Estimated PFS at 5 years was 94.2% with I+V, 80.6% with I, and 62.4% with FCR. OS is also trending toward a benefit for I+V. The results of the FLAIR study were simultaneously published in the New England Journal of Medicine.

o   Arnon P. Kater, MD, PhD updated the Phase 3 GAIA/CLL13 study. As background, GAIA/CLL13 trial previously showed superior PFS for venetoclax-obinutuzumab (GV) and GV + ibrutinib (GIV) compared to chemoimmunotherapy (CIT) and venetoclax-rituximab (RV) in fit treatment-naive patients (pts) with CLL and without TP53 aberrations. No significant PFS differences were observed between GV and GIV at prior data cuts but GIV was associated with more cardiac adverse events. In the analysis presented at EHA2026, at a median time of 63.8 months PFS continued to be superior for GV and GIV compared to CIT. In addition, GIV now showed a significantly longer PFS compared to GV. Estimated 5-year PFS rates were 50.7% (CIT), 57.4% (RV), 69.8% (GV) and 81.3% (GIV). No statistically significant differences in OS were observed between the treatment arms.

o   The results of a Phase 1/1b study assessing the combination of next-generation BTKi zanubrutinib and BCL2i sonrotoclax (BGB-11417) in R/R MCL were presented by Raul Cordoba, MD, PhD. Encouraging safety and antitumor activity were seen at RP2D with an ORR of 78% and a CR rate of 70%. At median DOR of 17.7 months, estimate event-free DOR at 24 months was 84%. The combination is currently being further evaluated in the Phase 3 CELESTIAL RRCML registrational study.

o   BTK degradation is an active field of clinical development, and multiple early assets were discussed at EHA2025. Of interest, Anna Maria Frustaci, MD presented results from the open label Phase 1/2 CaDAnce-101 study assessing BTK degrader BGB-16673  in a range of B-cell malignancies. In the Phase 1 portion in heavily pre-treated R/R Waldenström Macroglobulinemia patients exposed to BTKi, BGB-16673 exhibited good antitumor activity with an ORR of 84.4% and VGPR 31.3%. A rapid biomarkers decline was seen with improvement of cytopenias and deepening of responses over time. Responses were independent of mutations in BTK, MYD88, CXCR4, and TP53. BGB-16673 was well-tolerated, and the study is ongoing.

Plasma cells neoplasia

• Newest Multiple Myeloma CART results

o   As presented earlier this month at ASCO25, anti-BCMA CART Carvykti could represent a potential functional cure for some modern day Relapsed Refractory Multiple Myeloma (RRMM) patients. Described as “from the hospice to a cure” by Sundar Jagannath, MD who presented the long-term follow-up data, one third of CARTITUDE-1 study subjects were still in complete remission at the 5-Year mark with no detectable molecular traces of disease. CARTITUDE-1 enrolled a heavily pre-treated population of RRMM patients who at the time of study initiation had a dismal expected PFS of only a few months.

o   Gurbakash Kaur, MD updated the IMMagine-1 study of anito-cel, a new BMCA-CART using an innovative synthetic ligand-binding D-domain maximizing transduction efficiency, CAR expression on the T-cell surface, and a fast off-rate. At a median follow-up of 12.6 months, anito-cel demonstrated deep and durable responses with an ORR of 97% and a sCR/CR rate of 68%. 93% of the MRD evaluable patients were negative at 10-5 or lower. Importantly, anito-cel exhibits so far an impressive safety profile for a CART: 85% of patients did not have a CRS, or had a maximum of a Grade 1; 92% did not have ICANS; no delayed non-ICANS neurotoxicities, Parkisonism, cranial nerve palsies, or Guillain-Barré syndrome; no immune effector cell-associated enterocolitis. The IMMagine-3 global Phase 3 study is now enrolling.

• T-cell engagers

o   Early data on JNJ-79635322 (JNJ-5322), a novel BCMAxGPRC5DxCD3 trispecific was presented by Rakesh Popat, MBBS, PhD.  In the First-In-Human study in RRMM, JNJ-5322 showed an ORR at the RP2D of 100% (≥CR of 70.4%) in R/R BCMA/GPRC5D naïve patients. Such high ORR is unheard of for TCEs in relapsed myeloma (rates reported so far for various agents are in the 60-75% range) and is more comparable to what is seen with Carvykti

JNJ-5322 appears to have an improved safety profile compared with approved TCEs targeting BCMA or GPRC5D. Of note, the dysgeusia typically observed with GPRC5DxCD3 talquetamab (Talvey) was minimal with JNJ-5322 due possibly to the tight enforced interlocking of the molecule to both BCMA and GPRC5D. The community will be looking with interest to updated results as the data matures.

o   TCEs combinations in the clinic for MM presented at EHA2025 included:

o   Shaji Kumar, MD updated the RedirecTT-1 study during the Late-Breaking session. In the largest study to date dedicated to patients with Extramedullary Disease (EMD), a true difficult-to-treat unmet need, the combination of teclistamab (tec) and + talquetamab (tal) showed an ORR of 78.9% (≥CR 54.4%), a 12-mo PFS 81.8% and an OS rate of 74.5%. Safety was manageable and findings consistent with known AE profiles for tec and tal.

o   Enrique Ocio MD, PhD updated the LINKER-MM2 study evaluating the combination of BCMAxCD3 linvoseltamab with carfilzomib. The combination was feasible and safety consistent with expected AEs for these agents. No significant increase in cardiac/cardiovascular events. At a median follow-up of 14.8 months, the combination of linvoseltamab and carfilzomib resulted in a 90% ORR with 76% ≥ CR and a PFS of 83% at 12 months. These results are now being validated in an expansion cohort and a randomized Phase 3 is being planned. Linvoseltamab is now approved in the EU and will be reviewed by the US FDA later this year.

o   Meletios Dimopoulos, MD reviewed the results of the MagnetisMM-6 study Part 1, evaluating the safety  of the combination of BCMAxCD3 elratamab (elra) with daratumumab and lenalidomide (EDR) in transplant-ineligible patients. The combination was safe and appears active with an ORR of 97.3% and 94.6% having a VGPR or better. CRS and ICANS events were all ≤ 2 and reversible. Part 2 of MagnetisMM-6 in which EDR will be compared to DRd is starting soon.

o   Aurore Perrot MD, PhD updated the TRIMM-3 study evaluating the combination of talquetamab (tal) with anti-PD-1 antibody cetrelimab (cet) in RRMM patients, including some with prior bispecifics exposure. Tal + cet elicited deep and durable responses with an ORR of 68% in subjects with prior bispecifics exposure, a median DOR of 12 months with 9-months DOR of 66% in patients with prior bispecifics exposure. The safety was manageable and profiles consistent with each individual agent. Higher induction of CD27 and lower expression of CD57 on CD8 T-cells suggest a greater T-cell reinvigorating potential and possible benefit in patients with prior bispecifics exposure who might have altered T-cell activity.

• As seen at ASC025, anti-CD38-containing quadruplets (quads) continue to strengthen their position as SoC for NDMM. The major studies presented at EHA2025 focused on combinations using a carfilzomib (Kyprolis) backbone as part of the quads and emphasized MRD results given last year’s FDA decision on MRD-negative complete response as an acceptable early endpoint for accelerated approval in MM trials:

o   Francesca Gay, MD, PhD updated the IsKia study (isatuximab-Kyprolis-Revlimid-dexamethasone, or Isa-KRd, versus Kyprolis-Revlimid-dexamethasone, or KRd) with a focus on the light consolidation portion of the study. Isa-KRd significantly increased the rate of MRD negativity (10-6) versus KRd post-light consolidation (74% Isa-KRd versus 64% with KRd). The benefits are seen even in the highest-risk patients. Isa-KRd light consolidation was well tolerated.

o   ADVANCE was presented by Ola C Landgren, MD, PhD . The trial enrolled NDMM patients independently of their transplant eligibility status. Subjects were randomized to Dara-KRd (DKRd) or KRd for 8 cycles after which they were transplanted if MRD positive, whereas transplant was deferred if they were MRD negative. MRD negativity rates (10-5) at landmark was 59% with DKRd and 33% for KRd. At 31.2 months median follow-up, 92% were progression-free with DKRd versus 83% with KRd. Quite remarkably all of the 306 patients were enrolled at only 7 institutions. The team is now looking toward the future with ADVANCE 2.0 registrational Phase 3 planned.

o   Aurore Perrot MD, PhD revisited the now published MIDAS study evaluating MRD-guided consolidation strategy after Isa-KRd induction. In MRD-negative patients following Isa-KRd induction, Autologous Stem Cell Transplant (ASCT) consolidation did not improve MRD negativity rate compared to continuing Isa-KRD. In MRD-positive patients, tandem ASCT did not provide additional benefits in terms of MRD negativity compared to single ASCT. Tandem ASCT was being used much less in the era of novel agents, and these results will possibly lead many to abandoning it altogether.

o   Lisa Leypoldt, MD, who won an EHA Young Investigator Award, presented the GMMG-CONCEPT study, the largest prospective trial to date of purely High-Risk NDMM. Isa-KRd induction and consolidation followed by Isa-KR maintenance induced high rates of 1-year and 2-year sustained MRD negativity: the MRD negativity rate after consolidation was 74.8% and overall 86.8% reached MRD negativity at any time point. PFS and OS data are still maturing with sustained MRD negativity associated with better PFS. Carfilzomib once-weekly dosing with 56mg/m2 led to more dose reductions but less dose discontinuations.

• Dr. Xavier Leleu discussed the IRAKLIA trial assessing delivery of isatuximab subcutanelously using a novel on-body delivery system. This Ph3 non-inferiority study met its endpoints especially with regards to efficacy and PK. The paper is now published online in the Journal of Clinical Oncology.

• Meletios Dimopoulos, MD updated the Phase III DREAMM-8 study of belantamab mafodotin (Blenrep) + pomalidomide + dexamethasone (BPd). The combination continued to demonstrate a clinically meaningful benefit versus pomalidomide + Velcade + dexamethose (PVd) in RRMM patients who had received ≥1 prior line. The benefit was maintained across key subgroups, including anti-CD38- and lenalidomide-refractory disease, and no new safety signals were observed. The data supports BPd as an option for patients with RRMM. Right after EHA2025 it was announced that Blenrep, which was withdrawn in 2022 following disappointing results from a confirmatory trial, will now face a FDA ODAC review meeting on July 17 before a potential return to the US market.

• Circulating Tumor Cells (CTCs) are emerging as novel prognostic biomarkers in plasma cell malignancies. Multiple studies were presented at EHA2025 including:

o   Luca Bertamini, PhD presented a European pooled CTC analysis of 2,446 ND MM cases, the largest study to date in myeloma.  Performed by the EU CTC Consortium in NDMM patients of different background treated with a variety of anti-myeloma agents at institutions across Europe, the study established the prognostic value of CTCs. CTCs as a continuous variable or log10 groups were prognostic, and they became even stronger predictors when including other factors such as cytogenetics, ISS and LDH.

o   CTCs also appear prognostic in AL Amyloidosis as presented by Ioannis V. Kostopoulos, PhD. In a study of 218 cases treated at the Department of Clinical Therapeutics in Athens, Greece, CTCs were detectable in 59% of patients with AL amyloidosis and the differential presence of CTCs had an independent prognostic impact for both EFS and OS. CTCs are less abundant than in MM and highly sensitive methods such as next-generation flow cytometry were needed. Patients with detectable CTCs had a 45% reduced probability of achieving MRD negativity post-therapy.

We will continue to follow the development of these and other hematology assets throughout the year.

Additional meeting notes available on request. Contact us at: info@hematocure.com