Indigenous CAR-T cell therapy: A Paradigm Shift for B-Cell Cancer Treatment in India

Published: Feb 2024

Cancer has been one of the most dreaded diseases for years. The National Institute of Health, reported 14,61,427 (crude rate:100.4 per 100,000) number of incident cases of cancer in India for the year 2022. One in nine people in India is likely to develop cancer in his/her lifetime. Lung and breast cancers were found to be the leading sites of cancer in males and females, respectively. Children aged 0-14 years are more likely to suffer from lymphoid leukemia, with boys exhibiting a 29.2% incidence rate as against 24.2% for girls. Considering 2020, the incidence of cancer cases is estimated to grow by 12.8% by 2025.   

In 2020, Global Cancer Observatory (GLOBOCAN), estimated an incidence of 19.3 million cancer cases globally. As per the report, India ranked third after China and the US. Also, GLOBOCAN predicted the number of cancer cases in India to reach around 2.1 million by 2040, marking a rise of 57.5 %. Thus, in an effort to develop an optimal cure research on immunotherapies was initiated, which were named as the ‘fifth pillar’ of cancer treatment, by many. The therapy is claimed to transform the cancer treatment landscape over the traditional procedure involving surgery, chemotherapy, and radiation therapy.

The immunotherapies strengthen the power of a patient's immune system to attack tumors. The therapy involves the use of immune system–boosting drugs, known as immune checkpoint inhibitors that potentially shrink and even eradicate, tumors in some people with advanced cancer. The response of these treatments can also last in some patients for years. These are widely used to treat cancer in the lungs, kidney, bladder or melanoma and lymphoma.

Another immunotherapy that has generated substantial excitement among researchers and oncologists is Chimeric Antigen Receptor (CAR) T-cell therapy. India has also adopted the therapy to its cancer treatment procedures, indigenously. The therapy is expected to reduce cancer-related mortality and revolutionize cancer treatment to save hundreds of lives.  

A number of clinical trials related to the therapy adoption have been conducted globally. Most of the trials were implemented in Asia and North America, reasoned by the prevalence of the most incidence cases of cancer in the regions. As, China and the US rank the highest in cancer incidence cases, these two are the major competitors in the development of CAR-T cells, supported by their robust infrastructure development. Canada is also contributing considerably to the increasing number of clinical trials in the North American region.

The Asian countries actively contributing to the research include Japan, South Korea, Malaysia, and Iran. However, the majority of the studies are in their early phase of development. The fact that more than 10.0% of the studies are not yet active, demonstrates the prospective growth in the business. 

Accessibility and Pricing of CAR-T Cell Therapy

The accessibility and pricing of cancer therapies including CAR-T cell therapy are largely affected by national boundaries. For instance, the estimated mean direct Out-Of-Pocket Expenditure (OOPE) incurred, on cancer treatment in India, per outpatient consultation and per episode of hospitalization was estimated as INR 8,053.0 ($101.0) and INR 39,085.0 ($492.0) respectively, in 2023. Per the patient annual direct OOPE incurred was estimated as INR 331,177.0 ($ 4,171.0). The two major contributors to the cost include diagnostics expenses (36.4%) and medicines expenses (45.0%), for outpatient treatment and hospitalization, respectively. 

The cost of treating CAR T-cell immunotherapy (CRS) in the US ranges from $30,000.0 to $56,000.0 per patient. The total treatment cost reaches up to $500,000.0 for patients with severe CRS. In Europe, the total medical cost of CAR T-cell therapy, including expenditure with adverse events, was €7,176,196.0 ($7,562,275.0), and €286,238.0 ($301,637.0) (when CAR T-cell acquisition cost was excluded), in 2022. Substantially higher healthcare costs were observed in the earlier stages of treatment, during the studies. Further, it was observed that 97.0% of the total medical cost corresponded to CAR T-cells drug’s acquisition costs. Inpatient care costs, including hematology and ICU hospitalizations, accounted for 57.5%, diagnostic and therapeutic procedures’ costs contributed 37.5%, blood tests and examination represented 15.6% and  9.9% was the cost incurred by the cell therapy procedures. 

Thus, the analysis of the total expenditure of the CAR-T therapy procedures, across different geographies highlights that the expenditure is significantly less in India. Also, the doctors in India claim, that the results of Indian CAR-T therapy matched considerably with those of the US. This has the potential to guide other low and middle-income countries, about manufacturing an affordable therapy. 

Cost- Effective CAR-T Therapy would be a Potential Driver for Medical Tourism in India

The NeXCAR19, an indigenously developed therapy for the treatment of relapsed/ refractory B-cell lymphomas and leukemia, would be available at 20 hospitals. This CAR-T cell therapy has reduced the cancer treatment by approximately 90.0%, making India part of the elite club of selected countries, to offer this treatment. The group of government and private hospitals offering this treatment in the first phase include Tata Memorial Hospital, Deenanath Mangeshkar Hospital in Pune, Rajiv Gandhi Cancer Hospital and Max Super Speciality Hospital in Delhi, Continental Hospitals in Hyderabad, American Oncology Institute and more. 

Thus the emergence of this therapy has significantly contributed to the development of the country’s healthcare landscape. Also considering its affordability as against the therapies offered by other countries, the therapy will result in the evolution of India as the most preferred medical tourism destination, significantly accelerating the industry’s growth. 

Case Diary of the First Patient Declared Free of Cancer

Dr. (Col.) V. K. Gupta, aged 64, a Delhi-based gastroenterologist, has been declared free of cancer cells, despite a failed bone marrow transplant in 2022. This was possible due to CAR-T cell therapy. He suffered from acute lymphoblastic leukemia, a cancer that impacts white blood cells, specifically lymphocytes. The therapy was conducted by Dr. Hasmukh Jain, hemato-oncologist and associate professor at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC), Tata Memorial Centre. The therapy has been approved by the Indian drug regulators. The therapy rendered an INR 42.0 lakh ($50.8 thousand) obligation, as against the treatment expense of INR 3.0-4.0 crore ($363.0 thousand- $484.0 thousand) abroad. The procedure has not yet delivered any major side effects, apart from some minor sinus-related issues, since its inception in November 2023. 

Developed by ImmunoAct, IIT Bombay, and Tata Memorial Hospital, the therapy has been administered to 15 patients in India. Three of them have successfully achieved cancer remission. The treatment is based on genetically reprogramming a patient's immune system to fight cancer. The effective therapy has significantly reduced the treatment cost, depreciating it by approximately ten times. 

The therapy was conducted at the Tata Memorial Hospital, making Gupta, the first commercial patient to achieve the status of ‘currently free of cancer cells’. ‘Currently’ denotes that it is still premature to be claimed as a lifelong cure. 

Gupta underwent the indigenously developed therapy named NexCAR19, for B-cell cancers (cancers that form in the immune system’s cells), such as leukemia and lymphoma. The therapy showed positive results for Dr. (Col.) Gupta in just 2 weeks, with a significant drop in the cancer count and a rise in the hemoglobin levels. 

The initial findings of the therapy suggest better survival chances and lower remission rates, for patients in the early stages of cancer. The actual success of the therapy would be determined by the end of two years. The estimation of the potential relapse timelines, for patients, if any would require the analysis of a huge volume of data across the years.  

The therapy has two crucial evaluation points when it comes to the final outcome. The first step takes place 28 days after the blood infusion with CAR-T cells, accompanied by a PET scan. However, none of the 15 patients is reported to have reached this milestone. The second evaluation point takes place after three months. The first three patients (including Dr. (Col.) Gupta) are in complete remission, demonstrating a significant positive outcome.

Encapsulating, the therapy has the potential to bring life to the distressed, while defending them both from the fatal effects of the disease and degraded finances. It can emerge as a hope as stated by Dr. (Col.) Gupta, ‘I feel like a soldier now — tired, but unwilling to give up.’ The doctors claim that the therapy is advantageous for those, on whom the traditional treatments like chemotherapy have failed, leading to a relapse. The commercial use of this therapy was approved by the Central Drugs Standard Control Organisation (CDSCO) in October 2023. At present, NexCAR19 is available at approximately 30 hospitals in more than 10 cities in India. Patients over the age of 15 are eligible for this one-time therapy.  The research related to similar therapies is still ongoing with many hospitals, including Chandigarh-based Postgraduate Institute of Medical Education and Research (PGIMER), are also conducting clinical trials in the use of CAR-T cell therapy.