EHA 2026 Late Breakers Deliver Practice-Shifting Phase 3 Data and Novel CAR T Approaches Across Hematology

Results both dramatic and nuanced of combination therapies and single agents across hematologic disease settings were presented during the late-breaking abstract session of the European Hematology Association (EHA) 2026 Congress. As introduced by session cochair Meritxell Alberich Jordà, PhD, these 6 presentations represent the top-scoring abstracts selected by peer review of more than 70 late-breaking submissions.

Phase 3 Evidence With the Potential to Shift Practice

Matthew Davids, MD, of Dana-Farber Cancer Institute in Boston, presented results of the phase 3 BRUIN CLL-322 trial of pirtobrutinib plus venetoclax-rituximab (PVR) vs venetoclax-rituximab alone (VR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma, with pirtobrutinib representing the first and only approved noncovalent Bruton tyrosine kinase (BTK) inhibitor. The 639 participants (PVR: n = 321; VR: n = 318) had a median of 2 prior lines of therapy, and nearly 80% had already received a covalent BTK inhibitor. The study’s primary end point was met, showing a progression-free survival (PFS) advantage in the PVR arm with a 45% reduced risk of progression or death (HR, 0.547; 95% CI, 0.400-0.748; P = .0001) as assessed by an independent review committee. Evaluation of measurable residual disease (MRD) is ongoing, but 52.1% of the PVR arm vs 35.0% of the VR arm had achieved undetectable MRD at 10^–6 by the end of treatment.

“Interestingly, I think the control arm is also very important here for VR, because this is the first time we’ve seen data in a post–covalent BTK inhibitor population, and the PFS rate of 72% is notably lower than what was seen in [prior studies], and I think that suggests that the patient population of this study was particularly high-risk,” Davids said. Results will be published in the Lancet.

Phase 3 PASHA trial data in the acute myeloid leukemia (AML) setting evaluated gilteritinib vs midostaurin in the first line of treatment, with presenter Marc Raiijmakers, MD, PhD, of Erasmus MC Cancer Institute in the Netherlands, noting that it represents the first randomized head-to-head comparison of a second-generation (gilteritinib) vs first-generation (midostaurin) FLT3 inhibitor. The trial’s 768 patients with FLT3-mutated AML had a median age of 59 years, and about two-thirds had intermediate- or high-risk disease. Although the primary end point of overall survival was not met (HR, 1.02; 95% CI, 0.81-1.28; P < .0864), results indicated longer event-free survival and longer relapse-free survival in the gilteritinib arm. Raaijmakers noted that these trends could suggest greater biological antileukemic activity of the second-generation agent and theorized that midostaurin’s postrelapse survival advantage may reflect “a higher percentage receiving salvage with gilteritinib or allogeneic stem cell transplant.”

In the relapsed/refractory multiple myeloma setting, the phase 3 SUCCESSOR-2 trial compared mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) to evaluate the advantage of adding the cereblon E3 ligase modulatory drug (CELMoD). The 479 patients (MeziKd: n = 225; Kd: n = 146) had all received at least 1 prior line of therapy for progression of their myeloma, and 26% of patients in the MeziKd arm were 75 years or older. The median PFS was 18.0 months with MeziKd and 8.3 months with Kd, for an HR of 0.48 (95% CI, 0.36-0.83; P < .0001), and response curves also favored MeziKd. Rates of neutropenia aligned with expectations, and only 1 patient had to discontinue treatment due to it.

Based on these findings, presenter Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece, emphasized the potential for mezigdomide as an agent that can be easily used across diverse care settings including community practice. In response to a question on where it could fit in the treatment paradigm, Dimopoulos said that “it’s very important to have active combinations of agents that have different mechanisms of action, different safety profiles, because the war against myeloma is a marathon.” Results are now published in the Lancet.¹

The phase 3 SENTRY trial evaluated selinexor plus ruxolitinib in myelofibrosis, which presenter Claire Harrison, MD, with Guy’s and St. Thomas’ NHS Foundation Trust in the United Kingdom, described as building on the COMFORT trial data presented at the 2011 EHA Congress showing the evidence for ruxolitinib,² which she called an excellent drug but one that has limited depth and durability of responses. In SENTRY, 235 patients were randomly assigned to receive selinexor plus ruxolitinib and 118 to receive ruxolitinib and placebo. The selinexor arm had an OR of 2.58 (95% CI, 1.60-4.17; P < .0001) of achieving splenic volume reduction of at least 35% from baseline, with responses observed as early as week 12. Patients in both arms reported similar improvement in symptoms, and transformation to AML was rare, at 1.7% in both arms.

“Overall survival benefit was appreciated as early as week 24, compared to ruxolitinib,” Harrison said. “This has not been demonstrated in a combination before.” Full results are now online in the Journal of Clinical Oncology.³

Phase 1 Data Show Future Applications of CAR T-Cell Therapy

The late-breaking session also featured early data from phase 1 trials showing the potential to harness chimeric antigen receptor (CAR) T cells in new ways.

Results of the first-in-human trial of LB2501, an in vivo CD19/CD20 dual targeting CAR T-cell therapy, in relapsed/refractory B-cell non-Hodgkin lymphoma, were presented by Lei Fan, MD, PhD, of the First Affiliated Hospital of Nanjing Medical University in China. He highlighted that an in vivo approach addresses manufacturing constraints by delivering CAR-encoding genetic material directly to immune cells within the patient instead of in a laboratory—exemplified by the median time from consent to infusion of just 17.5 days. All 6 patients receiving a higher dose of LB2501 showed overall response, with 83.3% achieving complete response, and deepening responses were observed across the ongoing follow-up. The most common adverse events were infusion-related reactions and cytokine release syndrome, all of which were grade 1 or 2; there were no dose-limiting toxicities or severe adverse events.

Given the superior outcomes in the higher-dose arm, Fan confirmed that the investigators’ next step will be to assess a higher dose, perhaps double the higher dose in this first trial. But these proof-of-concept findings, Fan said, “support further development of LB2501 as a potential first-in-class, off-the-shelf, single-infusion, no lymphodepletion, outpatient use in vivo dual CAR T-cell therapy for relapsed or refractory B-cell lymphoma.”

While the use of CAR T in oncology has exploded over the past decade, application in noncancer hematologic settings has been limited but an avenue of emerging interest.⁴ Data presented by Jinhui Shu, of the Huazhong University of Science and Technology in China, explored the use of a B-cell maturation antigen CAR for refractory primary immune thrombocytopenia, an autoimmune condition that causes low platelet counts and bleeding. Of 8 patients receiving the agent, 4 had evaluable data, and all achieved complete response, although 1 patient relapsed at 9 months. No severe adverse events were reported.

“After CAR T exhaustion, the whole microenvironment was remodeled,” Shu said.

References

1. Dimopoulos MA, Schjesvold F, Fu C, et al. Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled trial. Lancet. Published online June 14, 2026. doi:10.1016/S0140-6736(26)01088-3

2. hHarrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798. doi:10.1056/NEJMoa1110556

3. Bose P, Ali H, Al-Ali HK, et al. Selinexor plus ruxolitinib in JAK inhibitor-naïve myelofibrosis: phase 3 SENTRY trial. J Clin Oncol. Published online June 2, 2026. doi:10.1200/JCO-26-01080

4. Baker DJ, Arany Z, Baur JA, Epstein JA, June CH. CAR T therapy beyond cancer: the evolution of a living drug. Nature. 2023;619(7971):707-715. doi:10.1038/s41586-023-06243-w