NexCAR19 (talicabtagene autoleucel) / ImmunoACT - LARVOL DELTA

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

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 Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Secondary Central Nervous System Lymphoma • TP53

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 Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases

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

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

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 Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Septic Shock

Apollo Cancer Centers Introduces CAR-T Therapy for Blood Cancer (Medical Dialogues) - "Apollo Cancer Centers in Visakhapatnam has introduced CAR-T cell therapy, marking a significant milestone as the first of its kind in Andhra Pradesh. This advanced treatment is designed for blood cancers that have not responded to conventional therapies, offering new hope to patients....Apollo Cancer Centers’ partnership with ImmunoACT has made this innovative treatment accessible to patients in Andhra Pradesh, offering them a renewed chance at recovery. While data on the effectiveness of Indian CAR-T cell therapies is still evolving..." "

Reimbursement • Hematological Malignancies • Leukemia • Lymphoma • Oncology

CAR-T Cell Therapy Accessibility: A Targeted Review of Access Challenges and Opportunities in APAC Region (ISPOR-EU 2024) - "India has introduced NexCAR19, a locally developed CAR-T cell therapy for B-cell lymphoma/leukemia, offered at a lower cost compared to other therapies... Given the high costs associated with CAR-T cell therapy, collaborative funding mechanisms among payers are essential for enhancing affordability and access. Governments can play a pivotal role by subsidizing hospital expenses, covering product costs, offering grants, and streamlining approval processes. The diversity in healthcare infrastructures across APAC underscores the need for tailored, context-specific strategies to facilitate equitable access to CAR-T therapies."

CAR T-Cell Therapy • Review • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Teen with cancer gets new lease of life as SUM Hospital performs eastern India's first CAR-T cell therapy (The Indian Express) - "Ananta Mahakud had always envisioned a bright future for his only daughter Truptimayee. His dreams came crashing down like a set of ninepins when the 15-year-old girl was diagnosed with acute lymphoblastic leukemia...Trupti is the fifth patient in the country and first in the eastern region to have undergone the groundbreaking therapy...Head of the department of Clinical Hematology and Bone Marrow Transplant Dr Priyanka Samal said after countless consultations, the girl was provided NexCAR19....Medical superintendent Dr Pusparaj Samantasinhar said SUM Hospital became the first hospital in Odisha to offer CAR T-cell therapy bringing this revolutionary treatment closer to home for patients who previously would have had to travel long distances, often abroad, and spend crores of rupees for such therapies. It is now available in the state within the affordable range, he added."

Reimbursement • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

ICMR signs MoA with industry and academic partners to advance first-in-human phase 1 clinical trials (Pharmabiz) - "In a step towards strengthening India’s clinical research ecosystem, the Indian Council of Medical Research (ICMR) has formalised Memorandum of Agreements (MoAs) with multiple sponsors under its Network of phase 1 clinical trials, marking a ground-breaking entry into first-in-human clinical trials for four promising molecules...These include collaborative research over a small molecule for multiple myeloma with Aurigene Oncology Limited...and CAR-T cell therapy advancement study for a new indication of chronic lymphocytic leukaemia with ImmunoACT....This network is designed to build and enhance India’s capacity to conduct early-phase clinical trials, supported by robust infrastructure and dedicated manpower at each trial site, ensuring smooth and effective operations."

Licensing / partnership • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Drug development in LMICs: could the emerging Indian model usher the southeast Asian region? (PubMed, Lancet Reg Health Southeast Asia) - "However, due to prolonged innovative stagnation, the entire drug development machinery faces challenges stretching all the way from arranging funds to persuading regulatory bodies. In this Viewpoint, we have tried to address a few of those issues and their potential solutions, with the intention to share our own experience which might be useful to other LMICs in connecting some adamant dots."

Journal • Review • Oncology

An Analysis of Infectious Complications Post-Treatment With Actalycabtagene Autoleucel (SOHO 2024) - "Patients receiving Actaly-cel primarily developed infections on days 0-28 after infusion. The majority of these were suspected or confirmed bacterial infections. The number of infections per patient did not correlate with ALC, IgG level at baseline, or the duration of neutropenia."

Diffuse Large B Cell Lymphoma • Oncology

India native CAR-T god! The first patient was almost "cured", and the cost was only 1/10 of the United States [Google translation] (bydrug.pharmcube.com) - "Tata Memorial Hospital and India Institute of Technology Mumbai, a partnership to form ImmunoACT, developed the product, which is now available in more than 30 hospitals in more than 10 cities in India....Dr. Gupta underwent a bone marrow transplant in 2022 but failed, paying 4.2 million rupees (about 350,000 yuan, about 1/3 to 1/4 of the price of the products on the market in China) for CAR-T treatment, and about 40 million rupees in Western countries...It is reported that the objective response rate of NexCAR19 in patients with relapsed/refractory B-cell malignancies is 67%, and the completion response rate is 52%...To be honest, compared with the remission rate of 80% or even more than 90% of other CAR-T movements, it is indeed a bit inadequate."

Clinical • Reimbursement • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Immunoact lays groundwork for India cell, gene therapy innovation (Bioworld) - "India’s first indigenous CAR T therapy is selling at around $50,000 per shot, nearly one-tenth of the price of top-selling CAR Ts in the U.S., and Immunoact founder and CEO Rahul Purwar told BioWorld he anticipates bringing the price down to as low as $20,000 per shot."

Commercial • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Regulatory landscape and challenges in CAR-T cell therapy development in the US, EU, Japan, and India. (PubMed, Eur J Pharm Biopharm) - "However, India's first indigenously developed CAR-T cell therapy, NexCAR19, for B-cell lymphoma or leukemia, approved and available at a low cost compared to other available CAR-T therapies, raises great hope in the battle against cancer. Several strategies are proposed to address the identified hurdles from global and Indian perspectives. It discusses the benefits of aligning regulatory requirements across regions, eventually facilitating international development and enabling access to this transformative therapy."

CAR T-Cell Therapy • Journal • Review • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Talicabtagene Autoleucel: First Approval. (PubMed, Mol Diagn Ther) - "Talicabtagene autoleucel (NexCAR19™) is a chimeric antigen receptor (CAR) T-cell therapy being developed by the Indian Institute of Technology, Bombay (IIT-B) and Immunoadoptive Cell Therapy (ImmunoACT) for the treatment of relapsed/refractory B-cell malignancies...Talicabtagene autoleucel was approved in India for the treatment of relapsed/refractory B-cell lymphomas and relapsed/refractory B-cell acute lymphoblastic leukaemia on 13 October 2023. This article summarizes the milestones in the development of talicabtagene autoleucel leading to this first approval for relapsed/refractory B-cell lymphomas and relapsed/refractory B-cell acute lymphoblastic leukaemia."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CAR T-Cell Therapy for Cancer in India; MTC Opens Doors for International Patients (EIN Presswire) - "Medical Tourism Corporation (MTC) is pleased to launch its initiative to open doors for international patients seeking CAR T-cell therapy in India for cancer treatment...The new-age therapy would offer significant cost savings of up to 90% to patients...In India, CAR T-cell therapy costs between USD$50,000 to $85,000 as compared to the United States, where the cost for the treatment is a whopping USD$450,000...MTC connects international patients with the top CAR T-cell therapy programs and specialists in India at affordable cost. The cost package, starting at USD$50,000, includes accommodation, meals, and therapy-related expenses....MTC advisors strive to ensure a hassle-free experience for patients and their companions from the time they land in India till the end of their treatment."

Commercial • Hematological Malignancies • Oncology