Qartemi (varnimcabtagene autoleucel) / August Pi i Sunyer Biomedical Research Institute, Immuneel Therap - LARVOL DELTA

Real-world experience with varnimcabtagene autoleucel (murine CD19 CAR-T) from India: A step towards enhanced patient access with excellent safety and efficacy (ASH 2025) - "Tocilizumab, steroids and anakinra usage was in 39%, 9% and 4% respectively. The real-world experience provides strong evidence of efficacy and safety of varnim-cel in B-NHL comparable with pivotal study. It also proves the robustness of trans-national ultracold chainlogistics, safe and effective clinical delivery and management systems for commercial rollout acrossmultiple centres in India to provide equitable access in South Asia."

Preclinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Disorders • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • Thrombocytopenia

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

Varnimcabtagene autoleucel in relapsed / refractory B-cell malignancies: Manufacturing experience from India (ASH 2025) - "Scheduling, delivery logistics, maintenance of ultracold chain logistics and closecollaboration with clinical sites are important for effective delivery of CAR-T cell therapy products andoptimizing outcomes. Varnim-cel has shown robust performance in clinical trials and sustained success incommercial manufacturing. This report reveals consistent success with manufacturing varnim-cel forpatients in areas of high unmet need enabling efficient clinical implementation."

Hematological Malignancies • Oncology • CD4 • CD8

Varnimcabtagene Autoleucel (ARI-0001) for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) and Richter Transformation (RT) (ASH 2023) - "Patients received lymphodepletion with fludarabine (90 mg/m2) and cyclophosphamide (900 mg/m2) followed by 0.1-1 (CLL) and 0.5-5 (RT) x10e6 CART19 cells/kg in single or fractionated administration (10%, 30% and 60%) in a single institution...At screening patients had a median age of 58 years (44-74), 47% were females, with a median of 4 prior lines of therapy (2-9) including ibrutinib (89%), venetoclax (53%), R-CHOP (58%) and allo-HCT (21%)...Tocilizumab and corticosteroids were administered in 44% and 17% of patients, respectively... Administration of the CART19 var-cel (ARI-0001) was feasible in 95% of CLL/RT patients, with robust and durable var-cel engraftment in 89% of treated patients, and durable complete responses observed in 61% of patients. These initial outcomes or var-cel in this population contrasts with the overall findings of CART19 therapy in CLL/RT and encourages to further develop var-cel on this high-risk population."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Richter's Syndrome • IGH • TP53

Real-World Outcomes of CD19-Targeted CAR T-Cell Therapy in Adult and Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia (B-ALL): Insights from the GoCART Coalition on Behalf of the PDWP, ALWP, and CTIWP of the EBMT (ASH 2024) - "Results : A total of 345 patients (173 adults and 172 pediatrics) received therapy from 2016 to 2023 with tisagenlecleucel (65.2%), varnimcabtagene autoleucel (25.8%), brexucabtagene autoleucel (5.5%), and others (3.5%)...Bridging therapy was administered in 86.4% (298) of patients based on high or low intensity chemotherapy (32.1% or 26.5%, respectively), inotuzumab-ozogamicin (13.4%), TKI (8.2%), involved-site therapy (intrathecal chemotherapy, radiotherapy, orchiectomy) (3.5%), and blinatumomab (2.6%), alone or in combination...Lymphodepletion was performed in all but one patient, based on fludarabine and cyclophosphamide regimens...These findings support the continued use and further investigation of CAR T-cell therapy in diverse clinical settings, emphasizing the importance of post-infusion strategies to sustain long-term remission. This will provide deeper insights into the factors influencing outcomes and help refine treatment protocols to improve patient care."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Impact of Salvage and Bridging Therapy in Adult Patients with Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL) Referred for Anti-CD19 CAR T-Cell Therapy: An Intention to Treat Analysis (ASH 2023) - "This includes patients intended to receive the academic varnimcabtagene autoleucel (var-cel) in the CART19-BE-01 trial and the consecutive compassionate use and hospital exemption programs, as well as with commercially available tisagenleuceucel (tisa-cel). Lymphodepletion was performed with fludarabine (90 or 120 mg/m2) and cyclophosphamide (900 or 1000 mg/m2), followed by the infusion var-cel or tisa-cel, respectively...At screening patients had a median age of 34 years (19-78), 45% were females, with a median of 3 prior lines of therapy (2-7) including inotuzumab (69%), blinatumomab (27%) and allo-HCT (84%)... To the best of our knowledge this could be one of the first studies focusing on the impact of ST and BT in adult patients with R/R B-ALL referred for CART19 therapy. These results suggest that the potentially synergistic impact of bridging therapy may be mediated more by the modulation exerted by BT on the proliferative kinetics of the disease rather than on the..."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Varnimcabtagene Autoleucel (IMN-003A): Differences in T Cell Subset Phenotype in B-ALL and B-NHL Cohorts Did Not Influence Efficacy Outcomes in the Phase-2 Study (IMAGINE) (ASH 2023) - "Differences in the manufacturing outcomes (CAR % transduction, fold expansion) and T cell phenotype (naïve and effector T EMRA cell subsets) were observed in Apheresis and FP, between the B-ALL and B-NHL cohorts. A higher fraction of relatively more differentiated T cell phenotypes of effector (T EMRA) and effector memory (T EM) and a lower fraction of naïve T cells in the B-NHL cohort and within CD8 T cells, reflects a manufacturing conundrum for B-NHL patients with a higher target dose and the CD4: CD8 ratio in the final product. However, these differences in the final product did not adversely impact the clinical responses at D+90 with equivalent efficacy in both cohorts."

Clinical • P2 data • Non-Hodgkin’s Lymphoma • Oncology • CCR7 • CD8

Factors Associated with Refractoriness or Relapse after Varnimcabtagene Autoleucel (IMN-003A) in Patients with Relapsed Refractory B Cell Malignancies: Phase 2 First-in-India Industry (IMAGINE) Study (ASH 2023) - "In the IMAGINE study, with ORR 80. 9% at primary endpoint and median PFS not reached, relapse was seen in 37. 5% pts with median PFS of 178 days."

Clinical • IO biomarker • P2 data • Hematological Malignancies • Infectious Disease • Oncology • CD20 • CD22 • CD4 • CD8 • IL6 • PD-L1

Varnimcabtagene Autoleucel (IMN-003A): Pharmacokinetic Profile with Predominant Naïve and Central Memory Phenotype Demonstrates Sustained In Vivo Persistence and Durable Responses in a First-in-India Industry Phase-2 Study (IMAGINE) (ASH 2023) - "A fractionated infusion of 1 x 10 6 CAR+ cells (IMN-003A)/kg for B-ALL cohort and 5 x 10 6 CAR+ cells (IMN-003A)/kg for B-NHL cohort was administered over 3 days as 10%, 30% and 60% fractions after Fludarabine-Cyclophosphamide lymphodepletion regimen (LR). Varnimcabtagene autoleucel manufacturing process results in a drug product characterized by highly pure T cells, with high proportion of naïve and central memory polyfunctional cells. In this industry-led first-in-India phase-2 study, var-cel resulted in a cytokine response with sustained in vivo proliferation and persistence resulting in robust and durable responses."

IO biomarker • P2 data • PK/PD data • Preclinical • CCR7 • CD4 • CD8 • IL6

Cytokine Profile Following Varnimcabtagene Autoleucel (IMN-003A) in Patients with Relapsed Refractory B Cell Malignancies in the First-in-India Industry Phase-2 Study (IMAGINE) (ASH 2023) - "This is the first-in-India industry study evaluating cytokine profile at multiple timepoints before and after var-cel infusion and its correlation with clinical CRS. As per published literature, IL-6 levels were significantly associated with clinical CRS and showed association with peak var-cel expansion. There was a sharp increase in both IL-6 and IL-10 levels in serum post infusion, concurrent with clinical CRS prior to peak var-cel expansion."

Clinical • P2 data • Hematological Malignancies • Oncology • CXCL8 • IFNG • IL10 • IL15 • IL1B • IL2 • IL6 • IL7 • TNFA

The Bengaluru Score - a Prognostic Predictive Score for Clinical Efficacy Outcomes Based on Discovery Cohort of Patients Treated with Varnimcabtagene Autoleucel (IMN-003A) in the Phase-2 (IMAGINE) Study (ASH 2023) - "The Bengaluru Score is probably the first predictive prognostic score for clinical efficacy outcomes and is based on multivariant statistical analysis in the discovery cohort of patients in the IMAGINE study integrating clinical, laboratory and translational data with a very high sensitivity, specificity and accuracy. The score highlights the role of overall T cell expansion in the final product for B-ALL (but not the T N+CM subsets on its own) and for B-NHL, disease burden and haematological reserve. This suggests that earlier use of varnimcabtagene autoleucel may positively influence efficacy outcome but needs to be proven in the real-world setting."

Clinical • P2 data • Infectious Disease • CD4 • CD8 • IL6

Reinfusion of Varnimcabtagene Autoleucel (IMN-003A) in Patients with Relapsed Refractory B Cell Malignancies Is Feasible with Sustained Responses (ASH 2023) - "B-ALL pt received Dasatinib, Inotuzumab and CNS prophylaxis. Preparative conditioning regimen for these 4 patients were: Fludarabine-Cyclophosphamide (n=1), with Rituximab (n=2) and Rituximab with Nivolumab (n=1)... Reinfusion of varnimcabtagene autoleucel (IMN-003A) is feasible, safe and well tolerated. Preparative conditioning regimen for reinfusion needs personalization guided by CAR persistence, disease biology (CD20, PDL1 expression) and haematological reserve. After reinfusion, prolonged B cell aplasia was observed with 100% ORR at D+28 in evaluable pts."

Clinical • IO biomarker • Anemia • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Thrombocytopenia • CD20 • PD-L1

Modified Endothelial Activation and Stress Index (mEASIX) Score and Immune Effector Cell Associated Haematotoxicity (ICAHT) Following Varnimcabtagene Autoleucel (IMN-003A), a CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in the Phase-2 Study (IMAGINE) (ASH 2023) - "3%) each received red cells, platelets, G-CSF and romiplostim; majority did not need supportive treatment...mEASIX score may be used as an early predictor of CRS for permissive use of Tocilizumab before onset of severe symptoms. This is the first-in-India industry study evaluating mEASIX and ICAHT in patients treated with CAR-T cell therapy. mEASIX score 1 at D+4 was mildly predictive of CRS. All patients developed ICAHT but only a small number of patients needed supportive treatment."

CAR T-Cell Therapy • IO biomarker • P2 data • Anemia • Hematological Disorders • Neutropenia • Thrombocytopenia • IL6

Hypogammaglobulinemia and Infection Risk in Relapsed Refractory B Cell Malignancy Patients Treated with Varnimcabtagene Autoleucel (IMN-003A), a CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in the Phase-2 Study (IMAGINE) (ASH 2023) - "This is the first-in-India report evaluating hypogammaglobulinemia and infection risk post CAR-T cell infusion. The IVIg usage and documented infections was more in responders. The safety and efficacy outcomes of varnimcabtagene autoleucel (IMN-003A) are consistent with reported outcomes of approved CD19 directed CAR-T cell therapies."

CAR T-Cell Therapy • Clinical • P2 data • Hematological Malignancies • Infectious Disease • Nephrology • Oncology • Septic Shock

Primary Analysis of Varnimcabtagene Autoleucel (IMN-003A) in Phase 2 Study (IMAGINE), a First-in-India Industry CD19-Directed CAR-T Cell Therapy for Patients with Relapsed Refractory B Cell Malignancies (ASH 2023) - "Cyclophosphamide (300 mg/m2) and fludarabine (30 mg/m2) on days -5 to -3 were used as preparative lymphodepletion regimen...Tocilizumab, steroids and anakinra usage was in 37.5% (n=9/24, majority for persistent G1 CRS), 8.3% and 4.2% respectively... Varnimcabtagene autoleucel (IMN-003A), a First-In-India Industry CD19-directed CAR-T Cell Therapy for RR BCM, has demonstrated manageable safety profile and durable efficacy outcomes with deep responses including absence of severe neurotoxicity. This offers a significant benefit over standard treatment options for patients with RR BCM."

CAR T-Cell Therapy • Clinical • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Thrombocytopenia

Patient-Derived Follicular Lymphoma Tumoroids: A Tool to Recapitulate Biological Features of Low and High-Grade Lymphoma (ASH 2024) - "The anti-CD19 CAR-T product ARI-0001 was able to adhere to the tumoroid's surface but shows moderate infiltration and e`icacy, compared to CART activity in Patient- Derived Lymphoma Spheroids lacking ECM. This indicates that ECM may be a crucial player in cell therapy evasion in lymphoma by preventing CAR-T cells from reaching their target cells, which is a common hindrance in solid tumors. In summary, we have developed a patient-derived model that can recapitulate both indolent and aggressive FL features, providing an in vitro model suitable to study disease biology and personalized therapy testing in the context of structural and cellular elements of the TME, while reducing animal usage."

Clinical • IO biomarker • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD40LG • IL21 • VIM

The CAR-Hematotox Identifies Patients at High Risk of Infectious/Inflammatory Complications in a Cohort of Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Treated with ARI-0001 (Varnimcabtagene Autoleucel) (ASH 2024) - "Finally, we did not find differences between high and low HT either in the expansion peak (median 6.66 cells/µl vs 3.53 cells/µl, p=0.3) or AUC at 30d (median 81.82 μl/l vs 61.59 μl/l, p=0.2). Conclusion : The CAR-HEMATOTOX score at lymphodepletion predicts inflammatory complications and transfusion dependence by identification of a high-risk group in our R/R BCP-ALL cohort, that can help us design individual prophylaxis and support strategies, as well as select patients for outpatient infusion and follow-up."

Clinical • Acute Lymphocytic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Real World" Outcome of Hematopoietic Stem Cell Transplantation after CAR19 T Cell Therapy in Children and Adults with B-ALL: A Gocart Coalition Study on Behalf of the PDWP, ALWP, and Ctiwp of the EBMT (ASH 2024) - "Results : Of 345 patients (173 adults and 172 children) infused with CART19 (Tisagenlecleucel in 65.2%, Varnimcabtagene autoleucel 25.8%, brexucabtagene autoleucel 5.5%, and others 3.5%), 113 subsequently received an HSCT (37 adults and 76 children; median age 13.5 years, IQR 8.2-22.2) at a median of 6.2 months (3.7-11.8) after CART19 infusion. The low NRM, with no differences between pre-transplanted and transplant naive patients, suggest that HSCT after CART19 is well tolerated, and represent a valid strategy to reduce the risk of relapse. As it remains unclear for which patients autologous CART19 cells remains a stand-alone treatment, future studies should focus on strategies for early identification of patients at higher risk of treatment failure."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

CD70 Deregulation in Follicular Lymphoma at Diagnosis Is Associated with Relapse and Opens New Avenues for Dual CD19-CD70 CAR-T Therapy (ASH 2024) - "Here we assessed the immune profile (Nanostring® nCounter) in formalin-fixed paraffin-embedded (FFPE)-derived biopsies in a series of FL patients at diagnosis, homogenously treated with immunochemotherapy (mostly R-CHOP), and followed at Hospital Clínic de Barcelona...Finally, to advance towards personalized therapies for these high-risk patients and taking advantage of the CAR-T program at our institution, we generated a dual CD19-CD70 CAR-T combining an approved academic product, ARI-0001 (Martinez-Cibrian N, Br J Haematol 2024), and a truncated CD27 protein...Ongoing work includes the optimization of the CRISPR protocol during the CAR-T generation and in vivo studies. In summary, this multipronged study has allowed us to uncover the prognosis potential of CD70, its biological role in FL patients and the generation of a novel dual CD19-CD70 CAR-T with therapeutic potential in FL as well as other B-NHL."

IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • CD27 • CD40LG • CD70 • CD8 • IL21 • IL4 • TNFRSF14

Second Infusion of CAR T-Cells in Patients with Relapsed /Refractory B-Cell Acute Lymphoblastic Leukemia: Results from a Gocart Coalition Analysis on Behalf of the PDWP, ALWP, and Ctiwp of the EBMT (ASH 2024) - "CART1 products were varnimcabtagene autoleucel (ARI-0001) (23), tisagenlecleucel (13), brexucabtagene autoleucel (1), and other experimental (2). These results show that CART2 is associated with low NRM and might be a bridge to SCT or other additional therapies. Updated results with data about subsequent therapies after CART2 will be presented at ASH meeting."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD22

VIRAL REACTIVATIONS POST-CAR-T IN PEDIATRIC POPULATION: EXPERIENCE IN A TERTIARY CARE CENTER (SIOP 2025) - " One hundred and two patients received CAR-T-CD19 therapy (Tisagenlecleucel=79, ARI-0001=23), and seven had viral reactivation...Three patients received cidofovir, two foscarnet, and two immunoglobulins... Among over 100 pediatric B-ALL patients treated with CAR-T, viral reactivation incidence was low (6%) and mostly asymptomatic. This may be attributed to periodic immunoglobulin administration, aiming for a pre-dose threshold of 8 g/L."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Leukemia • Pediatrics

CAR-T CELL THERAPY IN CHILDREN WITH PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA WITH MEF2D::BCL9 FUSION GENE POSITIVITY: EXPERIENCE OF A TERTIARY CENTER (SIOP 2025) - "After bridging chemotherapy and 1 cycle of inotuzumab, she achieved MRD <0.01% and received CAR T-cell therapy (ARI-0001)...Case 2: A 4-year-old girl was primary refractory and received CAR T-cell therapy(Tisagenlecleucel) with pre-infusion MRD of 8%... Despite treatment with CAR T-cells, none of our patients achieved durable remission. Further studies with larger cohorts are needed to assess the prognostic value of this genetic subgroup in CAR T-cell therapy."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Pediatrics • Sarcoma • Septic Shock • Solid Tumor • BCL9 • MEF2D

Enhancing CAR-T Cell Therapy Through PD-1 deletion and Controlled IL-15 Expression. (ESGCT 2024) - "The CAR utilized in this work, CAR ARI-0001, is a second-generation CAR specific for CD19...We also showed that controlled IL-15 expression under PD-1 endogenous promoter reverses these deficiencies, making pdTRUCKIL-15 cells better suited to confront PDL-1+ tumors, ensuring prolonged survival and persistence. This strategy represents a significant advance in CAR-T cell engineering, offering a platform that could be applied to other PDL-1+ cancer types."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • BCL2L1 • BCL2L11 • IL15 • PD-1 • PD-L1

Addressing Cellular Resource Competition to Enhance Dual Transgene Expression in CAR-T Cells (ESGCT 2024) - "To investigate this hypothesis, we co-transduced T cells with various combinations of CAR constructs, each driven by the same promoter and with similar construct sizes, including ARI-0001 targeting CD19, ARI-0002 targeting BCMA (both 4-1BB-based CARs developed at Hospital Clínic de Barcelona-IDIBAPS), and CD28-based CARs targeting HER2 or mesothelin...Ultimately, we demonstrated that using different MOIs for the co-transduced CARs can effectively generate dual-targeting CAR T-cells with balanced populations of each CAR when using the co-transduction technique. These preclinical findings highlight the critical importance of carefully controlling lentiviral quantities in manufacturing T cells or other cells harboring multiple transgenes, to prevent resource saturation and maintain intact endogenous expression."

CAR T-Cell Therapy • IO biomarker • Infectious Disease • HER-2 • MSLN

Insertion site profile analysis of lentiviral vector transduced ARI-0001 (autologous CAR19-T cells) infusion products (ESGCT 2024) - "Nevertheless, continued monitoring of site-integration profile in CAR-T cell products is granted. Also, understanding the molecular basis of viral vector integration mechanism and integration-site preferences is key to develop safer viral vectors for future gene therapies."

Viral vector • Gene Therapies • Hematological Malignancies • Immunology • Primary Immunodeficiency