Hematologists Detail Practice-Shaping Data That Emerged at EHA 2026 (VIDEO)

Pivotal data shared across multiple myeloma, large B-cell lymphoma (LBCL), and myeloproliferative neoplasms (MPNs) took the spotlight during the 2026 EHA Congress, along with key updates in other hematologic malignancies.

To help recap some of the biggest themes and data to emerge from EHA 2026, OncLive^® asked experts from across the hematologic oncology field to share their biggest takeaways from the meeting, including:

• Emmanuel Bachy, MD, PhD, a professor in the Department of Clinical Hematology at Lyon Sud Hospital in France
• Claire Roddie, PhD, FRCPath, MBChB, MRCP, an associate professor in hematology at University College London, an honorary hemato-oncology/cell therapies consultant at University College London Hospitals, and clinical science director of CAR-T and Vector at the Centre for Cell, Gene and Tissue Therapeutics/Royal Free Hospital
• Peter Voorhees, MD, of the Hematology, Medical Oncology (Cancer) Department at Atrium Health and a professor of cancer medicine at Wake Forest University School of Medicine in Charlotte, North Carolina
• Claire Harrison, MD, a professor of myeloproliferative neoplasms and clinical director at Guy’s and St Thomas’ NHS Foundation Trust
• Ryan D. Cassaday, MD, a physician and professor in the Clinical Research Division at Fred Hutchinson Cancer Center, as well as a professor in the Division of Hematology and Oncology at the University of Washington School of Medicine in Seattle

“Coming to meetings like [EHA], it's very interesting to see different strategies that are being explored by other investigators, and coming from the United States, [it is helpful] to see a bit more of an international flavor, getting to see how some of my European colleagues are facing some of these challenges,” Cassady said. “[We can compare] some of the similarities of how we do things, but also some of the differences. In a venue like this, it is very interesting.”

LBCL

Results from EPCORE DLBCL-1: A randomized phase 3 study of epcoritamab vs investigator’s choice chemoimmunotherapy in patients with relapsed/refractory large B-cell lymphoma (Abstract S235)

Epcoritamab-bysp (Epkinly) monotherapy significantly improved PFS compared with investigator’s choice of chemoimmunotherapy (CIT) in patients with relapsed or refractory LBCL, meeting one of the dual primary end points of the phase 3 EPCORE DLBCL-1 trial (NCT04628494).¹

At a median follow-up of 38.6 months for the epcoritamab arm (n = 168) and 28.2 months in the CIT arm (n = 178), the median PFS by independent review committee was 3.5 months (95% CI, 2.9-4.6) with epcoritamab vs 3.0 months (95% CI, 2.9-4.1) with CIT (stratified HR, 0.74; 95% CI, 0.60-0.92; P = .0059).

The CR rate was 38% with epcoritamab vs 26% with CIT (nominal P = .0032). Although the coprimary end point of OS was not significantly different between the arms (stratified HR, 0.96; 95% CI, 0.77-1.20; P = .7285), investigators noted this result was confounded by COVID-19 mortality and greater use of subsequent therapies in the CIT arm. A post hoc analysis adjusting for both factors yielded a median OS of 16.7 months vs 9.5 months, respectively (stratified HR, 0.76; 95% CI, 0.59-0.99).

“We were [eagerly] awaiting for the presentation of the epcoritamab [data] from the EPCORE DLBCL-1 study,” Bachy said. “[Findings] showed a positive result for PFS [with] epcoritamab as a single agent. This was a great presentation from Christopher P. Fox, PhD, MBChB(Hons), FRCP, FRCPath, [of the University of Nottingham in the United Kingdom].”

Tafasitamab plus lenalidomide and R-CHOP for patients with previously untreated diffuse large B-cell lymphoma (DLBCL): results from the phase 3 frontMIND study (Abstract S101)

Tafasitamab-cxix (Monjuvi) in combination with lenalidomide (Revlimid) and R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) generated a statistically significant improvement in progression-free survival (PFS) compared with R-CHOP alone in patients with newly diagnosed, high-risk DLBCL, according to data from the phase 3 frontMIND trial (NCT04824092).²

At a median follow-up of 35.2 months, the tafasitamab-based regimen (n = 448) led to a 25% reduction in the risk of disease progression or death vs R-CHOP alone (n = 451; HR, 0.75; 95% CI, 0.59-0.96; P = .0194). The 2- and 3-year PFS rates were 71.1% and 67.3%, respectively, for the experimental regimen; these respective rates were 62.9% and 60.7% for R-CHOP alone.

Event-free survival was also significantly improved with tafasitamab-based treatment (HR, 0.79; 95% CI, 0.64-0.97; P = .0260), and interim overall survival (OS) data favored the tafasitamab arm (HR, 0.85; 95% CI, 0.63-1.14; P = .2703). The final OS analysis is planned at 5 years. Notably, the addition of tafasitamab and lenalidomide did not compromise R-CHOP delivery, with a median relative dose intensity of 100% in both arms.

“The frontMIND study comparing tafasitamab plus lenalidomide combined with R-CHOP, as compared with R-CHOP, was a positive result in terms of PFS [for] the primary end point,” Bachy said.

Multiple Myeloma

Successful in vivo CAR-T generation and MRD clearance with KLN-1010 across diverse baseline T-cell phenotypes in relapsed/refractory multiple myeloma (Abstract S185)

Treatment with the BCMA-directed, in vivo CAR T-cell therapy KLN-1010 drove deep minimal residual disease (MRD)–negative responses in patients with relapsed or refractory multiple myeloma, according to data from the phase 1 inMMyCAR trial (NCT07075185).¹

Unlike traditional CAR T-cell therapy, KLN-1010 uses lentiviral particles to generate anti-BCMA CAR T cells within the patient, eliminating the need for leukapheresis, ex vivo manufacturing, and lymphodepletion.

Among evaluable patients (n = 18), the overall response rate (ORR) was 100%, including a stringent complete response (sCR) rate of 22%, a CR rate of 6%, a very good partial response (VGPR) rate of 22%, and a PR rate of 50%; among those with at least 4 months of follow-up (n = 6), the sCR rate was 67%, and the VGPR rate was 33%.

MRD-negative bone marrow responses at a sensitivity of 10⁻⁵ were observed in 100% of evaluable patients (n = 14). No grade 3 or higher cytokine release syndrome was reported across the 3 dose levels, and investigators characterized the safety and tolerability profile of the off-the-shelf product as favorable and supportive of outpatient dosing.

“For me, the biggest development in the [hematologic oncology] space is in vivo CAR T. That's the [area] that I want to be following closely,” Roddie said. “Our labs at University College London are engaged heavily in developing the kind of tools to make [in vivo CAR T-cell therapy] a reality in the United Kingdom, that's my big area of focus right now.”

MajesTEC-9: a phase 3 study of teclistamab monotherapy vs pomalidomide/bortezomib/dexamethasone or carfilzomib/dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM) (Abstract S195)

Teclistamab-cqyv (Tecvayli) monotherapy produced significant improvements in PFS and OS compared with investigator’s choice of standard-of-care (SOC) pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or carfilzomib (Kyprolis) plus dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy including daratumumab (Darzalex) and lenalidomide, according to data from the phase 3 MajesTEC-9 trial (NCT05572515).³

At a median follow-up of 17.3 months, teclistamab (n = 296) reduced the risk of disease progression or death by 71% vs SOC (n = 297; HR, 0.29; 95% CI, 0.23-0.38; P < .0001); the median PFS was not reached vs 8.2 months, with 18-month PFS rates of 69.8% vs 26.9%, respectively. Teclistamab also reduced the risk of death by 40% (HR, 0.60; 95% CI, 0.43-0.83; P = .0020), with 18-month OS rates of 79.2% vs 68.6%. The bispecific antibody generated deeper responses as well, producing an ORR of 84.5% vs 54.2% and a CR–or–better rate of 65.9% vs 16.8%.

"[MajesTEC-9] is a study that addresses the issue: what do you do when a patient has disease that's anti-CD38 antibody refractory? The patients who were enrolled in MajesTEC-9 had disease that was, largely, refractory to lenalidomide, but also to anti-CD38 antibodies, as well,” Voorhees said. “You can imagine a patient who's progressing [frontline] therapy [stemming from the phase 3] MAIA [NCT02252172], CEPHEUS [NCT03652064], or IMROZ [NCT03319667] trials. [The phase 3] MajesTEC-3 [NCT05083169] and MonumenTAL-3 [NCT05455320] trials used daratumumab-based combinations [with a bispecific antibody], so that doesn't really apply to this [anti-CD38 refractory] population. MajesTEC-9 looked at teclistamab [monotherapy] vs SOC in that patient population, and there we see a clear improvement in PFS and OS in favor of teclistamab. This represents a wonderful option for patients who are not only lenalidomide refractory, but also anti-CD38 antibody refractory.”

MPNs

Mutant calreticulin-specific monoclonal antibody, INCA033989, produces clonal molecular responses that correlate with clinical responses in patients with myelofibrosis (Abstract S216)

INCA033989—a first-in-class, fully human, Fc-silenced IgG1 monoclonal antibody that selectively targets CALR mutations in complex with the thrombopoietin receptor—was well tolerated and generated robust spleen, symptom, anemia, and molecular responses in patients with CALR-mutated myelofibrosis, according to data from 2 ongoing phase 1 studies (NCT05936359; NCT06034002).⁴

The agent was evaluated as monotherapy in patients who were relapsed/refractory/intolerant to or ineligible for JAK inhibitor therapy (n = 83), as well as in combination with ruxolitinib in those with a suboptimal response to prior ruxolitinib (n = 21). No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached; 84% and 76% of patients remained on monotherapy and combination therapy, respectively, and the most common grade 3 or higher toxicities were cytopenias, which generally occurred in patients with preexisting cytopenias.

Among patients treated with monotherapy (n = 69), 55% achieved a spleen volume reduction of at least 25%, and 39% experienced a reduction of at least 35% as their best response. Furthermore, 53% of evaluable patients (n = 70) had a best total symptom score reduction of 50% or greater; and 60% of evaluable anemic patients (n = 40) achieved an anemia response, most of which were major responses.

“We saw…a strong signal with regard to spleen and symptom responses, but also allele burden reductions, great tolerability, improvements in anemia, and also changes in the allele burden and improvements in the bone marrow morphology,” Harrison said. “This is an exciting agent for patients in the future, and there will be both a frontline and a second-line study in myelofibrosis coming up. Watch out for that and [data for] the other CALR-targeting therapies, which will hopefully be coming up later [in 2026].”

References

1. Spencer A, Harrison S, Lim S-L, et al. Successful in vivo CAR-T generation and MRD clearance with KLN-1010 across diverse baseline T-cell phenotypes in relapsed/refractory multiple myeloma. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S185.
2. Lenz G, Trněný M, Burke JM, et al. Tafasitamab plus lenalidomide and R-CHOP for patients with previously untreated diffuse large B-cell lymphoma (DLBCL): results from the phase 3 frontMIND study. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S101.
3. Touzeau C, Mina R, Hungria V, et al. MajesTEC-9: a phase 3 study of teclistamab monotherapy vs pomalidomide/bortezomib/dexamethasone or carfilzomib/dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM). Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S195.
4. Nangalia J, Harrison C, Gotlib J, et al. Mutant calreticulin-specific monoclonal antibody, INCA033989, produces clonal molecular responses that correlate with clinical responses in patients with myelofibrosis. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S216.
5. Fox CP, Inchiappa L, Ferhanoğlu B, et al. Results from EPCORE DLBCL-1: randomized phase 3 study of epcoritamab vs investigator’s choice chemoimmunotherapy in patients with relapsed/refractory large B-cell lymphoma. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S235.