Pushing The Boundaries In Cell Therapy: CAR-T Updates From EHA 2025
By Ivo Carre, Hymlaire Lamisere, and Kasia Koczula, Lifescience Dynamics
The 30th European Hematology Association (EHA) Congress in Milan highlighted a more mature CAR-T therapy landscape, where rapid manufacturing, durable responses, and improved safety profiles are converging to challenge long-standing treatment sequences. Several indications were updated, including non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), where next-gen assets ranging from dual targeting to rapid manufacturing, or neurotoxicity mitigation, aim to offer novel therapeutic options for earlier intervention with broader patient access.
ATALANTA-1: Seven-Day Manufacturing And High Fresh Product Rate May Signal A New Era Of CAR-T For Non-Hodgkin Lymphoma
Galapagos’ GLPG5101, a second generation anti-CD19 CAR, demonstrated robust efficacy with 95% of patients (n=61) receiving an infusion, 95% (n=59) of which received a fresh product, 89% within seven days and 7% within eight to 21 days, and none of the patients receiving a fresh product required bridging therapy.
Among efficacy-evaluable patients (n=42), overall response rate was 69% in diffuse large B-cell lymphoma (DLBCL) , 95% in follicular marginal zone lymphoma (MZL), and 100% in mantle cell lymphoma (MCL), while complete response (CR) rates reached 54%, 95%, and 100% respectively.
Grade ≥3 cytopenia was the most common treatment emergent adverse event (TEAE), while high-grade toxicities were shown to be rare, with only one Grade≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICAN) event being observed, while low-grade events were seen in 41% and 18% of patients respectively. Partnered with a dropout rate of just 4.7%, significantly lower than historical CAR-T trials, this suggests a highly manageable safety profile and potential use in the outpatient setting.
GC012F In High-Risk MM: 100% Response, 95.5% sCR, And Universal MRD Negativity In First-Line Setting
GC012F, a dual-targeting FasTCAR-T therapy against B-cell maturation antigen (BCMA) and CD19, is gaining attention as a potential first-line treatment for newly diagnosed multiple myeloma (NDMM), particularly in transplant-ineligible elderly patients. At EHA 2025, Gracell Biotechnologies presented early data from its single-arm Phase 1 trial demonstrating deep responses and encouraging safety in this difficult-to-treat population.
In eight evaluable elderly newly diagnosed MM patients, GC012F achieved a 100% overall response rate and 100% minimal residual disease-stringent complete response rate (MRD-sCR), with all patients reaching undetectable MRD. MRD negativity was achieved across all dose levels, with durability supported by ongoing responses past 12 months in multiple patients.
The safety profile also was favorable, with all CRS events noted to be Grade 1 and resolved within eight days, while no ICANS or neurotoxicity were observed. The most common Grade ≥3 hematologic adverse events included neutropenia (75%), leukopenia (38%), and thrombocytopenia (38%), with minimal non-hematologic toxicity.
This study is notable as one of the few CAR-T trials in elderly transplant-ineligible NDMM patients, a population historically underserved due to often being excluded from cellular therapy trials because of age or frailty. All patients received standard induction of chemotherapy with revlimid, velcade, dexamethasone (RVD) prior to CAR-T infusion, and maintenance with lenalidomide was initiated in responders.
These early findings reinforce the potential of GC012F to shift treatment paradigms in frontline MM, offering a high-efficacy, low-toxicity alternative to transplant-based strategies, with the added benefit of rapid FasTCAR manufacturing. Further evaluation in larger randomized trials will be key to validating GC012F’s role in this setting.
Carvykti Hits The Five-Year Mark: One-Third Of Patients Remain Progression-Free
Ciltacabtagene autoleucel (Carvykti), a BCA-directed CAR-T therapy, has become an established brand for the treatment of multiple myeloma following its approval in 2022. During EHA 2025, Johnson & Johnson presented the anticipated long-term following data from its CARTITUDE-1.
Carvykti continues to demonstrate unmatched durability in relapsed/refractory MM (RRMM) based on long-term CARTITUDE-1 follow-ups with 33% of patients (32/97) of patients with historical median progression-free survival (mPFS) of
Importantly among these patients and over the course of the additional 28-month median follow-up period, no new cases of Parkinsonism or cranial nerve palsy were reported, while two cases of second primary malignancy (SPM) and neurologic events (not related to Carvykti) and four Grade ≥3 infections (not related to Carvykti) were reported, showing a durable and manageable safety profile.
Of particular interest was guidance around earlier use of Carvykti potentially helping extend long-term remission through fitter CAR-T cell profiles and improved effector-to-target ratios, with ongoing CARTITUDE-5 and 6 trials evaluating the potential for Carvykti to demonstrate cure and replace transplant.
Anito-cel: A Safer BCMA CAR-T With No Delayed Neurotoxicity And Deep Responses
Anitocabtagene autoleucel (Anito-cel), a next-generation BCMA-directed CAR-T using a novel synthetic D-domain binder, is emerging as a promising therapeutic option in RRMM. At EHA 2025, updated data from the Phase 2 registrational iMMagine-1 study underscored its potential to deliver deep, durable responses with an impressively favorable safety profile.
Anito-cel achieved a 97% overall response rate (ORR) and 68% stringent complete response/complete response (sCR/CR) rate in a heavily pretreated population (median five prior lines, 100% triple-class refractory), with 93% of evaluable patients achieving MRD negativity at 10⁻⁵ sensitivity. Moreover, at 12 months, progression-free survival and overall survival rates were 79.3% and 95.2%, respectively.
Importantly, the safety profile was well tolerated. No Grade ≥3 CRS was reported, with 85% of patients experiencing only Grade 1 or 2 CRS, resolving within a median of two days. ICANS events were rare (8%) and low-grade, with no cases of delayed or high-grade neurotoxicity, including no Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome observed during the median follow-up of 12.6 months (up to 29 months).
In contrast to early-generation CAR-Ts, Anito-cel’s D-domain architecture enables compact, efficient CAR expression and rapid tumor engagement with reduced immune activation, contributing to its safety and efficacy balance.
With Anito-cel now advancing to the global Phase 3 iMMagine-3 trial against standard-of-care regimens, the therapy is well positioned to become a best-in-class BCMA CAR-T, particularly for patients who are older, frail, or at risk of neurologic events, which may also expand the eligible population for curative-intent CAR-T therapy in multiple myeloma.
Together, EHA 2025 and ASCO 2025 marked a pivotal inflection point for CAR-T cell therapy, showcasing how innovation is reshaping the therapeutic landscape across hematologic malignancies. At EHA, updates demonstrated the evolution of CAR-T beyond its salvage roots, with milestones including seven-day delivery in NHL, frontline potential in MM, and sustained five-year remissions, all underpinned by improvements in design, speed, and tolerability. Meanwhile, ASCO 2025 further accelerated momentum with compelling data on dual-targeting constructs and off-the-shelf allogeneic platforms. Notable highlights included Kite Pharma’s KITE-363, a bicistronic CD19/CD20-targeted CAR-T achieving high response rates in R/R LBCL, and RD06-03, an allogeneic CD19 CAR-T showing 100% MRD-negative responses in R/R B-ALL with no major safety concerns. These advances, along with promising activity in high-risk and antigen-escape populations and early signals in solid tumors, underscore a new era for CAR-T — one defined by broader accessibility, earlier-line integration, and curative-intent strategies within and beyond traditional indications.
About The Authors:
Ivo Carre, Ph.D., is a senior business analyst at Lifescience Dynamics in London, with a doctorate in neuroscience from the UKDRI and over two years of biopharma consulting experience. He has supported various clients across several indications, including oncology, neurology, and rare diseases, with expertise in competitive intelligence, market research, and market access.
Hymlaire Lamisere, Ph.D., is a senior business analyst at Lifescience Dynamics, with a doctorate in immunology and over three years of consulting experience in the biopharmaceutical industry. He has supported clients across oncology, cardiometabolic, and rare diseases, with expertise in competitive intelligence, market research, and strategic advisory. His work spans pipeline strategy, conference intelligence, and cross-functional insight generation to inform commercialization and medical strategy.
Kasia Koczula, Ph.D., is an engagement manager at Lifescience Dynamics, bringing over eight years of consulting experience in the life sciences sector. She holds a Ph.D. in hematological oncology and has worked across a broad range of therapy areas, including oncology, cardiovascular diseases, and rare diseases. Kasia specializes in competitive intelligence, market research, and strategic advisory services, supporting clients with evidence-based insights to drive informed decision-making.