cesnicabtagene autoleucel (ARI0002h) / August Pi i Sunyer Biomedical Research Institute - LARVOL DELTA

Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells. (PubMed, Br J Haematol) - "Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. Patients with QIP-MS(+)/BM-based NGF(-) showed a non-significant shorter median progression free survival than those with QIP-MS(-)/BM-based NGF(-). In summary, we show the first experience to our knowledge demonstrating that QIP-MS could be particularly useful as a non-invasive technique when evaluating response after CAR T-cell treatment in MM."

CAR T-Cell Therapy • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

EFFICACY AND SAFETY OF ARI0002H, AN ACADEMIC BCMA-DIRECTED CAR-T CELL THERAPY WITH FRACTIONATED INITIAL THERAPY AND BOOSTER DOSE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2022) - P1/2 | "Cyclophosphamide (300 mg/m 2 ) and fludarabine (30 mg/m 2 ) were used as lymphodepletion regimen...Tocilizumab and corticosteroids were administered in 76% (mainly for persistent grade 1 CRS) and 12% of pts, respectively...7 pts (29%) improved their response after reinfusion. Conclusion ARI0002h is the first European academic CART for RRMM that has demonstrated deep and durable responses and a favorable safety profile, including the absence of neurotoxicity and the feasibility of a second booster dose."

CAR T-Cell Therapy • Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Genetic Disruption of Blimp-1 Drastically Augments the Persistence and Anti-Tumour Efficacy of BCMA-Targeting CAR-T Cells (ASH 2022) - P1/2 | " Stimulated T cells transduced with ARI2h, an in-house anti-BCMA CAR that is currently being explored in a clinical trial for relapsed/refractory MM (NCT04309981), were electroporated with either Cas9 alone (WT) or Cas9 + Prdm1-targeting sgRNA (Blimp-1 KO)... Genetic disruption of Blimp-1 caused anti-BCMA CAR-T cells to maintain a memory-like phenotype that retained effector function, even following repeated challenges with tumour cells. As a result, Blimp-1 KO CAR-T cells were considerably more effective than WT CAR-T cells at treating advanced MM in a murine model. Overall, we conclude that using gene editing to restrict Blimp-1 expression represents a promising strategy to enhance the sustained efficacy of anti-BCMA CAR-T cells."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CCR7 • GZMB • IFNG • IL2 • IL7 • IL7R • PRDM1 • TNFA

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. (PubMed, Lancet Oncol) - P1/2 | "ARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach."

CAR T-Cell Therapy • Journal • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Novel Coronavirus Disease • Oncology

Biomarkers of efficacy and safety of the academic BCMA-CART ARI0002h for the treatment of refractory multiple myeloma. (PubMed, Clin Cancer Res) - "Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes."

Biomarker • IO biomarker • Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma. (PubMed, Blood Adv) - P1/2 | "These results highlight the importance of EMD evaluation by [18F]FDG-PET/CT before and after CAR T-cell infusion. NCT04309981, and EudraCT, 2019-001472-11."

FDG PET • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

EFFICACY AND SAFETY OF CESNICABTAGENE AUTOLEUCEL (ARI0002H), AN ACADEMIC BCMA‑TARGETED CAR T‑CELL THERAPY, IN RELAPSED/REFRACTORY LIGHT‑CHAIN AMYLOIDOSIS (EHA 2026) - "Cesni-cel (3x10 6 CAR+ cells/kg) was administered in three fractions (10%, 30%, 60%), after lymphodepletion with fludarabine (30mg/m 2 ) and cyclophosphamide (300mg/m 2 ) on days –6 to -4. Table 1 Table 1 . Variables; median (range) At diagnosis At screening Age (years) 52 (49–66) 58 (50–66) Heavy and light chain isotype, n(%) IgG/IgA/IgD/BJ Lambda 2 (40)/ 1 (20)/ 1 (20)/ 1 (20) 5 (100) Serum M protein (g/L) 15.5 (13–24) 2.5 (0–20) Involved FLC (mg/L) 389.5 (147–3471) 352 (54–967) Bone marrow plasma cells (%)* 29 (8–96) 14.5 (5–48) NT-proBNP (pg/mL) 647 (211–21186) 277 (192–949) Interventricular septum thickness (mm) 13 (7–14) 13 (9–15) 24h proteinuria (g/24h) 2.37 (0.2–2.37) 0.8 (0.18–11.4) Organic disease Heart, n (%) Kidney, n (%) Muscular, n (%) Gastrointestinal, n (%) Total affected organs 3 (60) 3 (60) 3 (1–4) 3 (60) 2 (40) 1 (20) 3 (60) 4 (2–4) Mayo stage, n (%) I II IIIa 4 (80) 1 (20) 3 (60) 2 (40) Revised Mayo stage 2012, n (%) I II III IV 3 (60) 1 (20) 1 (20) 2..."

CAR T-Cell Therapy • Clinical • Amyloidosis • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Renal Disease

IMPACT OF BRIDGING THERAPY AND DISEASE RESPONSE ON OUTCOMES AFTER ARI0002H BCMA CAR-T IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2026) - "BT was administered in 46/69 (67%): cyclophosphamide bolus (48%), pomalidomide-based (28%), carfilzomib- based (15%), and chemotherapy (6.5%); all received a single cycle. Figure 1. Kaplan–Meier curves for progression-free survival (left) and overall survival (right) according to bridging therapy use (A), response to bridging (B), response category (C), and bridging regimen (D)."

CAR T-Cell Therapy • Hematological Malignancies • Multiple Myeloma

MARIBAVIR FOR PRE-EMPTIVE TREATMENT OF CYTOMEGALOVIRUS REACTIVATION IN CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY RECIPIENTS (EHA 2026) - "NHL-B 19 (76) MM 6 (24) Prior lines 2 (1-2) CAR-T product Ide-cel 1 (4) Ari0002h 2 (8) Axi-cel 20 (80) Cilta-cel 2 (8) Bridging therapy 23 (92) CRS ≥ 2 11 (44) ICANS ≥ 2 8 (32) Tocilizumab 18 (72) Tocilizumab dose (mg) 1200 (600–1600) Corticosteroids 23 (92) Corticosteroid dose (dexamethasone-equivalent, mg) 180 (70-360) Other CRS/ICANS therapy 14 (58) Siltuximab dose (mg) 1540 (1200–1550) Anakinra dose (mg) 2450 (1775–3125) ICU admission 8 (32) . Summary/Conclusion In this small retrospective cohort, maribavir provided effective viral control with minimal toxicity, supporting its use as a safe pre- emptive option for CMV reactivation in heavily immunocompromised CAR-T recipients. Larger prospective studies with comparative cohorts are needed to confirm these results."

CAR T-Cell Therapy • B Cell Non-Hodgkin Lymphoma • Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Organ Transplantation

Cesni-cel (ARI0002h) in ultra-high-risk multiple myeloma with plasma cell leukaemia or central nervous system involvement. (PubMed, Br J Haematol) - "Median progression-free survival (PFS) and overall survival (OS) were 10.5 and 15.9 months respectively. ARI0002h induces deep responses in relapsed uHRMM, supporting inclusion of PCL and CNS-MM in clinical trials."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Leukemia • Multiple Myeloma • Oncology • Rare Diseases • Transplantation

Academic BCMA CAR-T (ARI0002h) achieves MRD-negative remission with sBCMA biomarker response in relapsed POEMS syndrome after double ASCT. (PubMed, Ann Hematol) - "This case supports BCMA-directed CAR-T therapy as a safe and effective salvage strategy in RR-POEMS following ASCT failure, even in an aggressive disease context. Clinical trial registration: Not aplicable."

Biomarker • IO biomarker • Journal • Minimal residual disease • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Inflammation • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Pain • Rare Diseases • Transplantation

A study investigating the safety and efficacy of academically-produced CAR T cells compared with standard treatment for patients with multiple myeloma whose disease has returned or not responded to previous treatments. (clinicaltrialsregister.eu) - P2/3 | N=126 | Not yet recruiting | Sponsor: Universitair Medisch Centrum Groningen

New P2/3 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Enhanced antitumoral activity of the academic CAR-T ARI0002h against normal and low BCMA-expressing myeloma cells after incorporating a transmembrane CD28 domain. (PubMed, J Immunother Cancer) - "Incorporating a CD28-TMD into the ARI0002h CAR enhances tumor control even in relapse models with downregulation of the target antigen, offering improved long-term disease management. This modification increases potency against MM tumor cell lines with both normal and reduced BCMA expression, demonstrating superior metabolic endurance and in vivo activity."

IO biomarker • Journal • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD8

Metabolic Fitness of the Final ARI0002h CAR-T Product Predicts Treatment Outcome in Multiple Myeloma (EHA-EBMT-CART 2026) - "Integrating metabolic and proteomic data supports metabolic fitness as an important driver of CAR-T efficacy, and suggests that metabolic assessment could inform future improvements in CAR-T manufacturing. Ongoing analyses will further validate and expand these insights."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CD4 • CD8

A Spheroid Model to Cultivate Multiple Myeloma Cells in a Stromal/Collagen-based 3D Scaffold and Assess Anti-BCMA CAR-T Cells Activity (EHA-EBMT-CART 2026) - "ARI0002h successfully infiltrated this barrier with no loss of cytotoxicity. This demonstrates the model's utility for cultivating MM cells in a 3D context and its immediate application for CAR-T toxicity assays, with future potential for immune studies and patient-derived models."

CAR T-Cell Therapy • IO biomarker • Stroma • Hematological Malignancies • Leukemia • Multiple Myeloma • Plasma Cell Leukemia • SDC1

Characteristics and Clinical Impact of Oligoclonal Band Appearance in Multiple Myeloma Patients Treated with the Academic CAR-T ARI0002H (EHA-EBMT-CART 2026) - "Baseline characteristics Figure 1 Conclusions : ​ The development of OCB is a frequent event in MM patients treated with ARI0002h CAR-T therapy. OCB emergence is associated with a trend toward longer PFS and OS, reaching statistical significance in patients whose OCB persist for more than two months."

Clinical • Hematological Malignancies • Multiple Myeloma

Boosting CAR T-cell Therapy in Multiple Myeloma Combining in silico Perturbation Predictions and Drug Repurposing (EHA-EBMT-CART 2026) - "Methods : Longitudinal single-cell RNA and TCR sequencing were performed on over 100,000 CAR⁺ and endogenous (CAR⁻) T cells from infusion product (IP) and post-infusion (Peak) samples of 11 MM patients treated with the academic anti-BCMA CAR T therapy ARI0002h ( Figure A )...In silico perturbation screening further identified Panobinostat, a histone deacetylase (HDAC) inhibitor, as a top-ranked compound predicted to attenuate IFN-driven dysfunction and restore functional transcriptional states in non-responder T cells ( Figure F–G ). Conclusions : This study establishes a precision immunotherapy framework integrating single-cell multi-omics profiling, ML and virtual pharmacogenomics to identify predictive biomarkers and rational drug combinations. Future integration of in vivo CRISPR knockout screens will enable systematic refinement of drug targets that enhance CAR T-cell fitness, paving the way for bioinformatics-driven clinical optimization of tailored cell therapies."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • IFNG • SLAMF7

Complete Response in Relapsed/Refractory POEMS Syndrome after ARI0002h, an Academic BCMA-directed CAR-T Cell Therapy: A Case Report (EHA-EBMT-CART 2026) - "After lymphodepletion with fludarabine (total dose 90 mg/m 2 ) and cyclophosphamide (total dose 900 mg/m 2 ), an infusion of 3x10 6 ARI0002h cells/kg was administered in a fractionated manner: 10% on day 0, 30% on day +3, and 60% on day +7. Conclusions : BCMA-directed CAR-T is a promising therapy for RR POEMS syndrome and could provide deep responses with low-grade toxicity. To our knowledge, this is the third POEMS syndrome patient worldwide to receive a CAR-T, the first treated with academic CAR-T, and the first treated with CAR-T after ASCT relapse."

CAR T-Cell Therapy • Case report • Clinical • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Rare Diseases • Thrombocytopenia

Serum HLC Analysis as a Practical Tool for Response and Immune Monitoring after ARI0002h AntiBCMA CAR-T Therapy (EHA-EBMT-CART 2026) - "Elevated dHLC at day 28 identifies patients at higher risk of progression, but these findings should be confirmed in larger cohorts. Humoral recovery was not observed by day 100, and analyses at later timepoints aim to clarify whether subsequent immune reconstitution may relate to CAR-T persistence, infection rates and long-term outcomes."

IO biomarker • Hematological Malignancies • Infectious Disease • Multiple Myeloma

Acute Kidney Injury in Patients with Multiple Myeloma Receiving Cesnicabtagene Autoleucel (ARI0002h) (EHA-EBMT-CART 2026) - "Fludarabine 90 mg/m 2 and cyclophosphamide 900 mg/m 2 (-6 to -4) was employed as LD in forty (85%) patients. Six (13%) required fludarabine reduction and one (2%) received bendamustine 180 mg/m 2 (-5 to -4)...Conclusions : AKI was observed in a quarter of patients, mainly due to infection and CRS. Most patients recover baseline renal function within the first week, highlighting the importance of early recognition and optimal treatment."

Clinical • Acute Kidney Injury • Bone Marrow Transplantation • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Endocrine Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hypertension • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Multiple Myeloma • Nephrology • Rare Diseases • Renal Disease • Septic Shock

Cesnicabtagene Autoleucel (ARI0002H) in Patients with Ultra-high Risk Multiple Myeloma (EHA-EBMT-CART 2026) - P2 | "Conclusions : ARI0002h induces response in relapsed uHRMM, which justifies trial design to bring CAR-T cells to frontline treatment. In this setting, GEM-PLASMACAR (NCT06830733) is an ongoing phase II trial evaluating the efficacy of cesnicabtagene autoleucel in patients with newly diagnosed primary PCL."

Clinical • IO biomarker • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Multiple Myeloma • Plasma Cell Leukemia

2025 Update of Cellular Immunotherapy for Plasma Cell Disorders. (PubMed, Turk J Haematol) - "Ide-cel and Cilta-cel are CAR-T cells directed against BCMA, having received FDA approval for RRMM based on the Phase 2 KarMMa and CARTITUDE trials, respectively...Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in-vivo proliferation capability, are regarded as very efficacious...The development of academic CAR-Ts such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness...To overcome these issues, strategies are being implemented, including combination therapy, the incorporation of gamma-secretase inhibitors etc. In conclusion, CAR-T treatments have evolved into an effective therapy modality being anticipated to be utilized..."

Journal • Amyloidosis • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • SLAMF7

Expanding the boundaries of CAR T-cell therapy: Implementation of an outpatient-at-home (OATH) model (ASH 2025) - "Eligible patients (pts) were adults with R/R B-cell precursor acute lymphoblastic leukemia (BCP-ALL) or multiple myeloma (MM) who met predefinedclinical criteria (ECOG 0–1, no active infections, availability of a trained caregiver, and low tumor burden).Pts and caregivers received pre-enrolment education, providing symptom detection tools, including thecaregiver-performed immune effector cell encephalopathy (ICE) score and an adverse event action plan.The protocol included AH lymphodepletion with fludarabine (30 mg/m²/d) and cyclophosphamide (300mg/m²/d) for three days, followed by fractionated infusions (10%, 30%, and 60%) of one of the academicCAR-T CD19-directed (varnimcabtagene autoleucel, ARI0001, 1x10⁶ CAR T cells/kg) or BCMA-directed(cesnicabtagene autoleucel, ARI0002h, 3x10⁶ CAR T cells/kg), depending on the underlying malignancy.Infusions were administered in a day care unit, with AH follow-up post-infusion.Pts were monitored via twice-daily telephone..."

CAR T-Cell Therapy • Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Multiple Myeloma

Isotype-specific heavy/light chain quantification identifies prognostic biomarkers after ARI0002h BCMA-directed CAR-T cell therapy in multiple myeloma (ASH 2025) - "Recovery of uninvolved HLCs in a subset of patients suggests thathumoral immune reconstitution may progressively occur over time. Further investigation will determinehow this immunological recovery relates to CAR T-cell persistence and impacts long-term clinicaloutcomes."

Biomarker • CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma

Multi-omic analysis reveals metabolic fitness of the ARI0002h BCMA CAR T-cell infusion product as a key predictor of clinical outcomes in multiple myeloma (ASH 2025) - "These findingssuggest that assessing CAR-T metabolism prior to infusion may help predict therapeutic response andguide future product optimization. Ongoing analyses will further validate and expand these insights."

CAR T-Cell Therapy • Clinical • Clinical data • IO biomarker • Omic analysis • Hematological Malignancies • Multiple Myeloma • CD4 • CD8 • GSTM1 • S100A9 • SDHC