The EBMT-EHA 8th European CAR T-cell Meeting took place in Palma de Mallorca, Spain, on 12–14 February 2026. Leading experts from around the globe came together to share the latest clinical and translational advances in CAR-T and cellular therapy. Read about some of the top updates from the event below!

A Phase I trial of CD19/CD22 bicistronic CAR T-cells in pediatric and AYA patients with R/R B-ALL

Immune escape presents a challenge when treating patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), especially those who have received prior CD19-targeted therapy. Dual-antigen targeting is therefore being investigated as an approach to prevent immune escape and improve patient outcomes. Bicistronic CAR T-cells (BiCis19/22) with improved preclinical dual-antigen targeting and cytokine production are being investigated in a Phase I trial (NCT05442515), and data from the dose-escalation cohort (11 patients) were presented at this year’s meeting by Alexandra Dreyzin, MD, National Institutes of Health, Bethesda, MD.¹

The median age of patients was 24.3 years (11.1-29.2 years), and all patients received at least two prior lines of therapy (55% had undergone stem cell transplantation and 36% had prior CAR exposure). Initially, the trial stratified patients by prior CAR T-cell exposure; however, this was changed to stratification by disease burden following severe dose-limiting immune effector cell-associated neurotoxicity (ICANS) in two of the first four patients treated.

Dr Dreyzin highlights that “…so far, there’s been 100% MRD negative complete response rate, and that includes both bone marrow disease and extramedullary disease”. To date, the results with this bicistronic CAR T-cell construct suggest that this approach is highly efficacious in R/R B-ALL. In patients with high disease burden, there is a risk of severe ICANS and immune effector cell-associated hemophagocytic syndrome (IEC-HS), which can be mitigated with dose reduction. Further investigation is ongoing.

An update on MDC-CAR-BCMA001 in R/R systemic AL amyloidosis

Another top abstract presented this year was in the field of amyloidosis, with Kiavasch Farid, MD, Heidelberg University Hospital, Heidelberg, Germany, sharing updated data on the treatment of patients with R/R systemic light chain (AL) amyloidosis with MDC-CAR-BCMA001, a novel anti-BCMA CAR T-cell construct.²

As part of a compassionate use program, seven patients were treated with a fixed dose of 800 × 10^6 CAR T-cells after lymphodepleting chemotherapy with fludarabine/cyclophosphamide or bendamustine. Six of the seven patients achieved an overall response, with three exhibiting a complete remission (CR) and three very good partial remissions (VGPRs). Additionally, all CRs were measurable residual disease (MRD)-negative. Furthermore, at a median of 116 days, organ responses (cardiac and renal VGPR and improvements in myopathy/neuropathy) were observed in four patients. Six out of seven patients are alive (one death occurred after progression to multiple myeloma), and five patients are in sustained remission after a median follow-up of 9.3 months. Regarding safety, all cases of cytokine release syndrome (CRS) were manageable and resolved with tocilizumab and/or dexamethasone. ICANS and higher-grade late hematotoxicity were not observed in this cohort. These findings support the continued investigation of MDC-CAR-BCMA001 in patients with AL amyloidosis and preexisting organ insufficiencies, and Dr Farid shares the details of an upcoming Phase I trial:

“And what’s really noteworthy about this trial is that we will also include patients who formally achieve an adequate hematologic response, for example, a VGPR, but who fail to achieve any kind of organ response or even show signs of organ progression, presumably due to continued clone activity.”

Zamtocabtagene autoleucel in R/R LBCL: data from the DALY 2-EU study

Zamtocabtagene autoleucel (zamto-cel) is an autologous tandem CD20-CD19-directed CAR T-cell therapy being investigated in the second-line setting for patients with transplant-ineligible R/R large B-cell lymphoma (LBCL) in the pivotal DALY 2-EU trial (NCT04844866).³ In this study, 82 patients were randomized to receive zamto-cel, while 78 received standard-of-care rituximab-gemcitabine-oxaliplatin (R-GemOx). Crossover from R-GemOx to zamto-cel was permitted and occurred in 29 patients. 

The primary endpoint of event-free survival (EFS) was met, with an EFS of 6.2 months (95% CI: 3.8–13.8) for zamto-cel and 2.5 months (95% CI: 2.0–3.4) for R-GemOx (HR 0.39; 95% CI: 0.27–0.58; p<0.0001) at a median follow-up of 17 months. Zamto-cel therefore demonstrated statistically significant superiority over R‑GemOx. Rates of Grade ≥3 CRS and ICANS with this construct were low (5.3% and 1.3%, respectively). At the CAR-T Meeting, Gloria Iacoboni, MD, PhD, Vall d’Hebron Institute of Oncology, Barcelona, Spain, reported the findings of cellular kinetic (CK) analyses from the DALY 2-EU trial:

“We observed that the peak CAR T-cell expansion was associated with achieving a complete response, so it was associated with efficacy, and I think, interestingly, it was associated specifically with those patients achieving a durable CR…So it definitely seems that the peak CAR T-cell expansion is playing a key role in terms of efficacy with zamto-cel…Persistence was also correlated with a higher chance of achieving a durable remission in patients …and when we looked at tumor burden, this, as with other products, also seems to play a role.”

Results of the Phase II CART19-BE-02 trial of var-cel (ARI-0001) in patients with R/R B-ALL

The multicenter, single-arm, Phase II CART19-BE-02 trial (NCT04778579) was conducted at nine academic centers in Spain and investigated the safety and efficacy of varnimcabtagene autoleucel (var-cel; ARI-0001), an autologous CD19-directed CAR T-cell therapy, in adult patients with R/R B-ALL.⁴

In this trial, var-cel was administered with adaptive intra-patient dose escalation, meaning each dose level was separated by at least 24 hours, and each fraction was contingent on safety criteria. Valentín Ortiz-Maldonado, MD, Hospital Clinic Barcelona, Barcelona, Spain, provides insight into this dosing approach:

“The other key distinctive feature was that we were using a fractionated adaptive interpatient dosing strategy, which, instead of giving a full dose of CAR T-cells in one go, we administer escalating fractions over several days with safety checks before each infusion. So with this approach, we basically reflect something very practical, which is that patients are biologically heterogeneous. And, you know, disease burden differs, expansion kinetics differs. So we designed a strategy to allow us to listen to the biology of patients in real time. And by doing this, it’s basically a CAR T-cell approach that adapts to patients and not the other way around.”

The primary endpoint of the study was CR with undetectable MRD (sensitivity of ≤10^-5) determined by flow cytometry at day 28 after var-cel infusion, assessed in patients who received at least one var-cel fraction. By data cutoff, the median follow-up from infusion was 8.6 months, and 27 patients (84.4%; 95% CI: 67.2-94.7) of the 32 who received at least one var-cel dose achieved a CR with undetectable MRD by day 28. Therefore, the study met its primary endpoint. In terms of safety, data from 33 patients were evaluated, and rates of Grade ≥3 treatment-emergent adverse events were low, with the most common being neutropenia (n=15), thrombocytopenia (n=7), anemia (n=5), and CRS (n=4). ICANS was observed in only one patient, and IEC-HS in two.

These results suggest that var-cel is an efficacious CAR-T construct for treating adult patients with R/R B-ALL, leading to deep remissions with a favorable safety profile and low rates of CRS or ICANS. The fractionated dose escalation used in the trial appears to preserve var-cel activity while limiting the incidence and severity of adverse events.

The selective targeting of T-cell malignancies using a TRBC1-directed CAR T-cell therapy

As is widely understood, T-cell malignancies prove difficult to target with immunotherapeutic approaches due to the overlap in antigens on malignant and healthy T-cells. Fratricide during manufacturing and the risk of severe T-cell aplasia in vivo have significantly slowed the development of CAR T-cell therapies in these diseases compared with B-cell malignancies, and several strategies are being explored to overcome these challenges. A novel approach involves the selective targeting of T-cell receptor β-chain constant region TRBC1 on malignant T-cells while preserving a functional T-cell compartment. This led to the development and preclinical evaluation of a TRBC1-directed CAR T-cell therapy (CAR-T-One), the results of which were presented at the CAR-T Meeting during the ‘Best Abstracts’ portion of the closing ceremony by Anna De Lucia, PhD student, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola, Italy.⁵

“In our preclinical work, this [clonotype-restricted targeting within the T-cell lineage] translated into robust killing of TRBC1-positive targets with the preservation of TRBC2 T-cells, and single-cell imaging confirmed that the cytotoxicity was strictly TRBC1-dependent. The practical insight is that TRBC1 provides a therapeutic window in which meaningful antitumor activity can be achieved while preserving a functional T-cell compartment.”

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