NexCAR19 (talicabtagene autoleucel) / ImmunoACT, Cipla - LARVOL DELTA

NPPA asks cos to revise prices of 17 drugs following BCD exemption (Pharmabiz) - "The list of drugs include ribociclib, abemaciclib, actalycabtagene autoleucel, tremelimumab, venetoclax, ceritinib, brigatinib..."

Commercial • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Small Lymphocytic Lymphoma

Cipla Ltd has entered into a strategic partnership with ImmunoACT on January 20 to launch talicabtagene autoleucel, an anti-CD19 CAR-T cell therapy, for the treatment of blood cancers across select African markets. (Scanx) - "Under the exclusive licensing and supply agreement, Cipla will commercialise the therapy through its subsidiary Medpro Pharmaceutica in three key African markets....Separately, Cipla faces regulatory scrutiny as the US Food and Drug Administration (USFDA) has made multiple observations at one of its facilities. The regulatory concerns include: Procedures to prevent contamination were not followed; Control systems designed to prevent contamination were deficient; Deficiencies in aseptic processing areas and laboratory controls; Failure to establish procedures to assure drug purity and quality; Inconsistent following of sampling plans and test procedures; Buildings used in manufacturing not maintained in good state."

FDA event • Licensing / partnership • B Acute Lymphoblastic Leukemia • Non-Hodgkin’s Lymphoma

Early post-infusion cytokine profiling predicts toxicity and outcomes in recipients of NexCAR19 (Actalycabtagene Autoleucel): A pilot study with point-of-care assay integration (ASH 2025) - "While cytokine kinetics have been well-characterized incommercial CAR-T products such as tisagenlecleucel and axicabtagene ciloleucel, no published studies todate have described cytokine profiles in recipients of NexCAR19 (Actalycabtagene autoleucel), a novelCD19-directed CAR-T cell product developed in India. Early post-infusion cytokine profiling in NexCAR19 recipients demonstrated predictive utility for keytoxicities and adverse clinical outcomes. Elevated IL-1β, IL-2, IL-6, and MCP-1 levels were significantlyassociated with HLH, cytopenias, infections, and mortality. The rapid turnaround of the point-of-carecytokine panel supports its feasibility in real-time clinical decision-making."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Septic Shock • Thrombocytopenia • IFNG • IL1B • IL2 • IL6 • TNFA

Tali-cel is a safe and effective therapy in patients with Relapsed/Refractory B-cell non-Hodgkin lymphoma that allows equitable access- a real-world experience from India. (ASH 2025) - "Background : Talicabtagene autoleucel (Tali-cel), a second-generation, humanized CAR-T cell therapytargeting CD19, was approved in India in October 2023 for the treatment of relapsed or refractory (r/r) B-cell malignancies...Mostpatients had received a median of 2 prior treatment lines (range: 1–7), including polatuzumab (14%), andstem cell transplantation (4%)...Tocilizumab was administered in 63%patients who developed CRS with median dose of 1 (range 1-3)...IVIG support was required in 34% patients and anakinra formanagement of IEC-HS was required 75% respectively...This real-world analysis demonstrates that tali-cel is a practical, effective, and well-tolerated treatmentoption for r/r B-NHL in India. As the first large-scale, multicenter evaluation of this therapy in the Indianhealthcare landscape, our findings support its broader implementation across various levels of clinicalpractice."

Clinical • Real-world • Real-world evidence • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Lymphoma • Non-Hodgkin’s Lymphoma

Early use of talicabtagene autoleucel in r/r B-acute lymphoblastic leukemia is cost-effective: Improved efficacy, reduced toxicity and healthcare resource utilization support affordable access (ASH 2025) - "Utilization of tocilizumab(72% vs. 62%), anakinra (26% vs. 24%), and IVIG (49% vs. 54%) was similar between groups, reflectingconsistent supportive management.Cost modelling revealed a 60% reduction in median hospitalization costs for early-relapse patients, drivenby shorter hospital stay, less ICU need, and fewer high-grade toxicities requiring intensive management.In this real-world cohort, patients with early relapse r/r B-ALL treated with tali-cel achieved more durableresponses, with higher remission rates and longer progression-free survival compared to those treatedlater in the disease course. In this real-world cohort, patients with early relapse r/r B-ALL treated with tali-cel achieved more durableresponses, with higher remission rates and longer progression-free survival compared to those treatedlater in the disease course. Importantly, early use was associated with lower toxicity, reduced healthcareresource utilization, and a significant reduction in overall..."

Clinical • Cost effectiveness • HEOR • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Leukemia

Advancing CAR-T Cell Manufacturing in Latin America: Current Landscape, Future Directions, and Challenges. (PubMed, Crit Rev Oncol Hematol) - "India's talicabtagene autoleucel program built domestic vector and cell production to lower cost and shorten timelines, Brazil coupled a mature regulatory pathway with accredited centers and an emerging national platform for vectors and plasmids, Mexico demonstrated feasibility of hospital based closed system production under national oversight; Colombia and Chile are developing academic pipelines and locally relevant targets...Finally, coordinated alliances among hospitals, professional societies, patient groups, academia, and industry are needed to secure policy support and public investment. Together, these measures provide with a realistic path to safe, equitable, and affordable access to CAR T therapy in Latin America."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology

CD 19 CAR T-Cell Therapy in R/R B Cell Malignancies : A Real World Experience from CAR T Working Group, Delhi Ncr ,India (ASH 2024) - "Indigenously developed humanized CD-19 CAR T-cell therapy ( Actalycabtagene Autoleucel , NexCAR-19, ImmunoACT) has become available very recently in India.We report here our early real world experience, of CAR T-cell therapy in RR DLBCL and RR B-ALL from 3 major cancer centres in northern India (Delhi-NCR CAR T working group).15 patients were treated DLBCL -12 , B-ALL -3 from January 2023 to June 2024...The median baseline IgG level was 779 mg/dl (475-1247) and median trough level post CAR T-cell infusion was 566 mg/dl (319-972).11/15 patients received debulking treatment ( Acalabrutinib -Lenalidomide in 3 , Polatuzumab based in 4, R-GEMOX in 2 , Venetoclax -Lenalidomide in 1 , orbital RT in 1 ALL with an orbital lymphomatous mass) while 8/15 received bridging therapy (VIPOR in 1, Gemcitabine -Cyclophosphamide in 1, GEMOX in 1 , Acalabrutinib Lenalidomide in 2, Pola-BR in 1, Procarbazine, Cyclophosphamide, Etoposide, Prednisone + Ara-c in 1 B-ALL) .CRS was seen in 10..."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Fibrosis • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Secondary Central Nervous System Lymphoma • TP53

Evaluating the Safety of HCAR19 (Now Actalycabtagene Autoleucel- Actaly-Cel™), a Novel Humanized CD19-Directed Chimeric Antigen Receptor T-Cells in Pediatric, Adolescents, and Young Adults with Relapsed/ Refractory B- Acute Lymphoblastic Leukemia (ESHA) - Report of Phase-1B (ASH 2023) - "Lymphodepletion was with Fludarabine (30mg/m 2) x 3-days and cyclophosphamide (500 mg/m 2) x 2-days...Those with ≥ Grade-2 CRS received tocilizumab with full recovery...In-vivo dynamics and toxicity profile of Actaly-cel showed robust activity and low cytokines corroborating with pre-clinical studies. A median dose of 5x10 6/kg Actaly-cel is proposed as the P2D."

CAR T-Cell Therapy • Clinical • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Novel Coronavirus Disease • Obesity • Oncology • Pediatrics • Thrombocytopenia • IFNG • IL6

High Efficacy and Excellent Safety Profile of Actalycabtagene Autoleucel, a Humanized CD19 CAR-T Product in r/r B-Cell Malignancies: A Phase II Pivotal Trial (ASH 2023) - "Patients received infusion of Actaly-cel two days after conditioning with fludarabine plus cyclophosphamide...Only 1(3%) patient required ICU admission, 2(6%) required vasopressor support, tocilizumab was administered to 18 (55%) patients, median 1 dose (1-4) and steroids were used in 5 (15%) cases... Actaly-cel demonstrated efficacy in r/r B-cell malignancies with a very favorable safety profile. The absence of ICANS, shorter duration of cytopenias and a lower incidence of grade 3/4 CRS makes it one of the safest CD19 CAR-T cell therapy products. Actaly-cel can improve the ease of delivery of CAR T-cell therapy in a wide-range of settings."

Clinical • P2 data • Acute Lymphocytic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Thrombocytopenia

Excellent Safety Profile of a Low-Cost Novel Humanized CD19 CAR T-Cell Therapy, Actalycabtagene Autoleucel : Potential Impact on Access and Feasibility (ASH 2023) - "After lymphodepletion (LD) with a fludarabine plus cyclophosphamide (FC) regimen for 3 days, patients received Actaly-cel at a target dose ≥ 5 million CAR-T cells/kg (upper limit; total 2 x109)...A single dose of tocilizumab was given to 36% (10/28) of patients and only 4% (1/28) received tocilizumab plus corticosteroids... Actaly-cel was efficacious, with no incidence of ICANS and manageable CRS across a wide dose range. More importantly, this study reported low HCRUs due to negligible ICU admission and shorter duration of hospitalization, ensuring potential usage of Actaly-cel in outpatient settings, and ultimately improving the access and feasibility of CD19 CAR-T cell therapy in resource constrained settings such as LMICs."

CAR T-Cell Therapy • Clinical • Hematological Malignancies • Lymphoma • Oncology

Establishing a CAR-T Cell Therapy Centre in a Resource Limited Setting: Barriers and Early Outcomes (ASH 2024) - "In October 2023, India's Central Drugs Standard Control Organization approved Acalycabtagene Autoleucel (NexCAR19) to treat relapsed or refractory B-cell leukaemia (B-ALL) and lymphoma...Seven (87.5%) patients received fludarabine plus cyclophosphamide, while one (0.12%) received bendamustine...Five (62.5%) patients paid out of pocket, supported by crowdfunding campaigns from our public education initiatives, while three (37.5%) were covered by insurance or reimbursement.Conclusions : Despite challenges such as high CAR-T costs, resource constraints, and patient affordability, the therapy was effectively implemented in an LMIC setting. Limitations included early-stage data, small sample sizes, and brief follow-up, yet the results highlight its potential for effective use in similar resource-constrained environments."

CAR T-Cell Therapy • B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Septic Shock

Talicabtagene Autoleucel (humanized CD19 CAR-T) As a Second Line Therapy in r/r B-Cell Lymphoma: Sub-Analysis from a Phase I/II Trial (ASH 2024) - "The requirement for tocilizumab and corticosteroids (cohort 1 : 10% vs cohort 2 : 6%) was comparable, whereas the transfusion support (cohort 1 : 30% vs cohort 2 : 44 %) and IVIG treatment (cohort 1 : 40% vs cohort 2 : 53%) was lower in the patients in cohort 1.The patients in cohort 1 showed higher peak expansion on Day 14 (median, cohort 1 : 2.56x105 vs cohort 2 : 0.57x105 copies/μg of DNA) and the levels further persisted until last follow-up. The CAR-T cell products from cohort 1 had a higher percentage of CD8+ naïve cells in apheresis as well as CAR-T cell product, which associated with robust CAR-T expansion and durable response.Conclusion : In this post-hoc analysis,Tali-cel was found to be more well-tolerated, more efficacious, and easier to deliver in the second line setting for r/r DLBCL. Given limited patients in each cohort, further study based on post-marketing surveillance is planned."

Clinical • P1/2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8

Real World Data of Novel Talicabtagene Autoleucel (humanized CD19 CAR-T) from India; Ensuring Equitable Access with Excellent Safety and Efficacy Profile (ASH 2024) - "Patients received a single infusion of Tali-cel at target dose of ≥ 5x106/kg, after conditioning with Flu-Cy or bendamustine. Conclusion : The real-world evidence further confirms the efficacy and safety of Tali-cel in B-cell malignancies. The manufacturing success and safe and effective clinical delivery allow the deployment of CAR-T cell therapy outside the clinical trial settings in India."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases

India Unveils Its First Indigenous CAR-T Cell Therapy, Paving the Way for Affordable Cancer Immunotherapy (The Economic Times)

Launch non-US • Acute Lymphocytic Leukemia

Incidence, Clinical Characteristics, and Risk Factors of Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS) in Patients Treated With Talicabtagene Autoleucel (Humanized Anti-CD19 CAR-T) (SOHO 2025) - "Among the affected patients, 94% (17/18) received anakinra as first-line treatment for a median duration of 10 days (range, 2-22), starting at 100 mg q8h; 23.5% (4/17) required dose escalation to a maximum of 200 mg q8h. IEC-HS is a serious but manageable complication of CAR-T therapy. Early recognition and targeted intervention are key to improving outcomes. Strategies for prevention and mitigation are critical for successfully managing CAR-T therapy."

Clinical • Acute Lymphocytic Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

INCIDENCE, CLINICAL CHARACTERISTICS, AND RISK FACTORS OF IMMUNE EFFECTOR CELL (IEC) ASSOCIATED HLH-LIKE SYNDROME (IEC-HS) IN PATIENTS TREATED WITH TALICABTAGENE AUTOLEUCEL (HUMANIZED ANTI-CD19 CAR-T) (EHA 2025) - "Among the affected patients, 94% (17/18) received anakinra as first-line treatment for a median duration of 10 days (range, 2 - 22), with most starting at 100 mg 8 hourly; 23.5% (4/17) required dose escalation to a maximum of 200 mg. Ruxolitinib was introduced as second-line therapy in 66.67% (12/18) (standard dose: 10 mg ), Steroids was used as third-line treatment in 38.89% (7/18) of cases... IEC-HS is a serious but manageable complication of CAR-T cell therapy. Early recognition and targeted intervention are key to improving outcomes. Elevated baseline inflammatory markers and increased disease burden were strongly associated with IEC-HS risk."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

REAL WORLD DATA OF THE SAFETY AND EFFICACY OF TALICABTAGENE AUTOLEUCEL (HUMANIZED CD19 CAR-T) IN RELAPSED/REFRACTORY B-ACUTE LYMPHOBLASTIC LEUKEMIA FROM INDIA. (EHA 2025) - "Patients received a single infusion of Tali-cel at ≥ 5x10^6/kg after conditioning chemotherapy with Fludarabine-Cyclophosphamide or bendamustine...To manage CRS of any grade, 88% (52/59) of affected patients were treated with tocilizumab... Tali-cel shows strong promise as a standard of care for leukemia, particularly in resource-limited settings. Real-world data from India demonstrates its effectiveness, manageable toxicities with minimal ICU admissions. Thus, Tali-cel offers an affordable and scalable solution for improving the outcomes of relapsed/refractory leukemia in India."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Oncology • Rare Diseases

SAFETY AND EFFICACY OF POLATUZUMAB VEDOTIN PLUS GLOFITAMAB AS BRIDGING THERAPY PRIOR TO TALICABTAGENE AUTOLEUCEL FOR RELAPSED/ REFRACTORY B-CELL LYMPHOMA (EHA 2025) - "Conventionally, patients received dexamethasone or radiation therapy, with recent studies supporting the use of combination chemotherapy and targeted agents...In cycle 1, Obinutuzumab (1000mg) or Rituximab (375mg/m2) on day 1, Pola (1.8mg/kg) on day 2 and Glofit on D8 (2.5 mg) and D15 (10mg) of a 21-day cycle, in subsequent cycles Pola (1.8mg/kg) and Glofit (10mg) on day 1 were administered...All CRS cases were managed with tocilizumab and supportive care... Pola+Glofit as bridging therapy in R/R BCL demonstrated high response rates, even after a single cycle, with sustained responses following Tali-cel infusion. The combination showed favourable safety profile with manageable toxicity."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Septic Shock

Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel™) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study. (PubMed, Blood Cancer J) - "Lymphodepletion utilized standard-dose fludarabine and cyclophosphamide. and P2D was determined as 5-10 × 106 HCAR19-cells/kg. CLINICAL TRIAL REGISTRATION: The study is registered in the Clinical Trials Registry- India (CTRI/2021/05/033348 and CTRI/2023/03/050689)."

Journal • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation

Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study (Nature, Blood Cancer J) - P1 | N=6 | CTRI/2021/05/033348 | "Primary endpoint was overall response rate (ORR) at day-30 on bone-marrow flow-cytometry. From May-2021 to September-2023 12 patients [median age-14 (range: 5–24) years] were enrolled with median bone marrow blasts 19.5% at screening. Cytokine release syndrome occurred in 10 (83%) patients, predominantly Grades 1–2, and Grade-2 immune-cell associated neurotoxicity (ICANS) in 1. All patients had Grade-3 cytopenia. ORR was 91.7% (11/12), complete response (CR) in 8 (66.7%) and partial response in 3 (25%). Seven of 8 CRs were at Dose-levels B and C, all of which were sustained till 12 months follow-up."

P1 data • B Acute Lymphoblastic Leukemia

Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study (Nature, Blood Cancer J) - P1 | N=6 | CTRI/2021/05/033348 | "Primary endpoint was overall response rate (ORR) at day-30 on bone-marrow flow-cytometry. From May-2021 to September-2023 12 patients [median age-14 (range: 5–24) years] were enrolled with median bone marrow blasts 19.5% at screening. Cytokine release syndrome occurred in 10 (83%) patients, predominantly Grades 1–2, and Grade-2 immune-cell associated neurotoxicity (ICANS) in 1. All patients had Grade-3 cytopenia. ORR was 91.7% (11/12), complete response (CR) in 8 (66.7%) and partial response in 3 (25%). Seven of 8 CRs were at Dose-levels B and C, all of which were sustained till 12 months follow-up."

P1 data • B Acute Lymphoblastic Leukemia

CD 19 CAR T-CELL THERAPY IN R/R B CELL MALIGNANCIES : A REAL WORLD EXPERIENCE FROM NORTHERN INDIA (EBMT 2025) - "Background: Indigenously developed humanized CD-19 CAR T-cell therapy ( Actalycabtagene Autoleucel , NexCAR-19, ImmunoACT) has now become available in India.We report our early real world experience, of CAR T-cell therapy in RR DLBCL and RR B-ALL from 3 major cancer centres in northern India (Delhi-NCR CAR T working group)...Median CAR T dose was 9 million/kg (2-17), .9/17 received bridging therapy (VIPOR in 1, Gemcitabine -Cyclophosphamide in 1, in 1 , Acalabrutinib Lenalidomide in 2, Pola-BR in 1,Pola-Cyclophosphamide -Rituximab in 1, Procarbazine, Cyclophosphamide, Etoposide, Prednisone + Ara-c in 1 B-ALL)...However at Day 90, 2 patient in the baseline CR group progressed.Out of those DLBCL who have completed 3 months follow up, 4 are in CR and 2 patients of these have completed 6 months in CR .4 patients of Refractory B-ALL , 1 Ph like and 2 P53 mutated , ( 62/F with 90 % blasts in marrow, 19 Y/M, 0.01 % MRD, 16 years /m, 60 % blasts) and another with treated CNS..."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • TP53

Talicabtagene autoleucel for relapsed or refractory B-cell malignancies: results from an open-label, multicentre, phase 1/2 study. (PubMed, Lancet Haematol) - "Talicabtagene autoleucel had a manageable safety profile and induced durable responses in patients with relapsed or refractory B-cell malignancies. This therapy addresses an important unmet need for patients with relapsed or refractory B-cell malignancies in India."

Journal • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Septic Shock • Thrombocytopenia

CAR T-cell therapy in LMICs: approval of talicabtagene autoleucel in India. (PubMed, Lancet Haematol) - No abstract available

Journal

A Discount on the Cost of Cancer: India's Homegrown CAR-T Cell Therapy. (PubMed, Blood Cell Ther) - "As a lower-middle-income country with a massive burden of cancer, India's NexCAR19 was a pivotal point in South Asian cancer history. From benefiting local patients with cancer to collaborations with neighboring countries, to prompting the manufacture of more CAR-T products, NexCAR19 has facilitated the fight against blood cancers in South Asia."

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