Insights on CAR T-Cell Therapy: Informative Session with the Experts at Fortis Hospital, Gurgaon

19 November,2024

Cancer care in India witnessed a groundbreaking milestone during the CAR T-Cell Therapy event hosted by Fortis Memorial Research Institute, Gurgaon. This remarkable event, attended by industry leaders and innovators, spotlighted CAR T-Cell Therapy, a revolutionary approach to treating specific blood cancers. The therapy has been introduced in India under the brand name ImmunoACT NexCAR19, thanks to the tireless efforts of a dedicated IIT Bombay team led by Mr. Sirish Arya, Mr. Rahul Purwar, and Mr. Atharv Karulkar. Their journey spanned over eight years of rigorous research and innovation, marking a monumental achievement in India's medical landscape.

What is CAR T-Cell Therapy?

Chimeric antigen receptor T-cell therapy, or CAR T-cell therapy, is an advanced treatment modality in which a patient's immune cells are modified to target and destroy cancer cells. This therapy has emerged as a hope for patients battling B-ALL (B-cell Acute Lymphoblastic Leukemia) and B-NHL (B-cell non-Hodgkin lymphoma), two aggressive forms of blood cancers.

Event Highlights

• Insights from the Innovators: The Director of ImmunoACT NexCAR19, Mr. Sirish Arya,  shared his invaluable insights on developing this cutting-edge therapy. With Mr. Rahul Purwar and Mr. Atharv Karulkar, the team from IIT Bombay has brought India's first indigenously developed CAR T-cell therapy to the forefront of global cancer care.
• Expert Perspectives: Renowned oncologists Dr. Rahul Bhargava and Dr. Vikas Dua elaborated on the workings of the therapy, including its process, benefits, and financial aspects. Their discussions shed light on how CAR T-cell therapy has transformed cancer treatment paradigms by offering a targeted, personalized, and highly effective solution.

NexCAR19: A Transformative Solution for Blood Cancers

Dr. Rahul Bhargava and Dr. Vikas Dua explained how NexCAR19 is a promising treatment for blood cancers, including:

• B-ALL (B-cell Acute Lymphoblastic Leukemia): A type of blood cancer primarily affecting immature white blood cells (lymphoblasts) in the bone marrow. Left untreated, it can lead to rapid disease progression and poor patient outcomes.
• B-NHL (B-cell Non-Hodgkin Lymphoma): This group of cancers originates in B-lymphocytes and is characterized by abnormal growth in lymph nodes or other tissues. Its aggressive nature makes early and effective treatment critical.

What is NexCAR19?

• NexCAR19 is a CAR-T Cell Therapy. It involves genetically modifying your body's T-cells in a controlled laboratory setting and then re-infusing the modified T-cells, which are empowered to identify and destroy certain cancerous B-cells.
• It is a prescription drug for treating specific relapsed or refractory B-cell non-Hodgkin's lymphomas and B-cell acute lymphoblastic leukemia when other standard treatments have failed. 
• ImmunoACT developed NexCAR19 in collaboration with IIT Bombay (Indian Institute of Technology Bombay) and Tata Memorial Centre, Mumbai. President Droupadi Murmu launched the therapy on April 4, 2024, at IIT Bombay. 
• The Central Drugs Standard Control Organization (CDSCO), a counterpart of the USA's FDA, approved NexCAR19 in October 2023 based on the results of two clinical trials. 

About ImmunoACT

ImmunoACT was established in 2018. It spun out of the Bioscience and Bioengineering Lab at IIT Bombay and was supported by the Society for Innovation and Entrepreneurship (SINE), an organization at IIT Bombay that fosters entrepreneurship. ImmunoACT offers affordable, life-saving cell and gene therapies. It is the culmination of research efforts that began in 2013.

From the initial design to the final product, research and development to clinical trials and commercialization, ImmunoACT is a fully integrated cell and gene therapy company that adheres to the highest global standards of cell therapy manufacturing. Their therapies against cancer are designed to train patients' immune systems to do the job they were always meant to do, i.e., destroy tumors. They encode the right instructions in the cells to fight specific cancers, preferably as single-dose treatments.

How Does NexCAR19 Work?

• Our body naturally makes T-cells (a type of white blood cell) as an advanced defense against viruses and cancer cells. As they mature, they develop specific receptors to target key signals on cancer cells. 
• However, cancers can hide themselves and escape the inbuilt defense mechanism of T-cells, which can result in the survival of cancer cells and a further increase in tumor burden.
• CD19 is a protein commonly present on the surfaces of certain cancers. 
• Scientists have designed unique proteins called chimeric antigen receptors (CARs), which are delivered by a vehicle to T-cells so that they can target and bind to CD19.
• NexCAR19 uses a specially designed and patented delivery vehicle called a lentiviral vector to genetically engineer the patient's T-cells. 
• These modified T-cells will express chimeric antigen receptors that target CD19. Now that they are trained, the T-cells will find and destroy cancer cells using their inbuilt processes.

What is the Treatment Process for NexCAR19?

The treatment process of NexCAR19 CAR T-cell therapy can be divided into three basic steps: leukapheresis, interim, and infusion and monitoring.

Treatment Consideration

NexCAR19 may be considered by your hematologist or medical oncologist if you are 15 years of age or older and were diagnosed with a B-cell non-Hodgkin's lymphoma or B-cell acute lymphoblastic leukemia and one of the following has occurred:

• Frontline treatment was not sufficient to achieve remission.
• Previous treatment failed to achieve any response or was followed by a relapse.
• Relapse occurred after a prior complete remission or after an earlier stem cell transplant.

Some of the clinical factors in choosing NexCAR19 as a potential option are:

• Patients must be generally fit to tolerate the therapy.
• They must have healthy and well-functioning vital organs.
• The nature and progression of the disease also play a role in deciding if CAR T-cell therapy is right for the patient.
• Other treatments performed before or after the therapy and their impact are also considered.

Treatment Planning

Your treatment team will schedule a cell collection process called leukapheresis based on the following factors.

• The existing burden of disease: If your disease burden is high, your treating physician might want to schedule the NexCAR19 treatment around another therapy to reduce this disease burden first.
• Timing of prior treatments: NexCAR19 is manufactured from your own T-cells. Certain prior immunotherapies or chemotherapies may negatively affect the quality and quantity of the T-cells. Your physician may accordingly schedule the collection of your cells and the treatment administration around these aspects to get the best possible T-cells to fight your cancer.

Leukapheresis

• Leukapheresis is the process of collecting white blood cells performed at the hospital.
• It is a day-care procedure that usually takes 4-6 hours. It is recommended that you wear loose-fitting attire for the procedure.
• ImmunoACT processes the leukapheresis sample within 24 hours. The hospital will inform you when manufacturing is proceeding.

Interim

• After Leukapheresis, NexCAR19 is usually manufactured within 19 days.
• In the Interim period, your physician may administer a bridging therapy to lower your disease burden.
• You will start receiving conditioning chemotherapy approximately five days before NexCAR19's infusion so that your body is ready for it.

Infusion and Monitoring

• NexCAR19 is usually infused on the 20th day. It is done via intravenous route and takes less than 30 minutes to complete
• Your physician may decide to have you hospitalized for 7 to 15 days to monitor and manage side effects.
• You may experience fever, muscle ache, dizziness, breathing difficulty, and tiredness within the first 2-3 weeks of infusion. Alert your physician if you start exhibiting these symptoms. You may receive medications, if required, to manage these symptoms. 
• Monitor your handwriting periodically to check for potential neurotoxicity.

Timeline of NexCAR19 Therapy

• Day 0: Patient enrolment is completed, and consent is taken at the hospital. White blood cells are extracted by a machine at the hospital and packed in a leukopak.
• Day 1 to 9: The leukopak is then shipped to ImmunoACT's manufacturing facility under refrigerated conditions. ImmunoACT's scientists select and activate the T-cells, then modify them using a safe lentiviral vector. This makes the T-cells express special receptors called chimeric antigen receptors (CARs) that target B-cell cancer. The cells are then cultured and multiplied until they reach a target dose.
• Day 9 to 19: The targeted T-cells, now NexCAR19, are cryopreserved and undergo extensive testing to ensure their identity, purity, safety, and potency. The product is then shipped to the hospital in an infusion bag under cryopreserved conditions.
• Day 20: NexCAR19 is administered via intravenous infusion. Prior to this, the patient receives conditioning chemotherapy to prepare their body for the treatment.

What is the Cost of CAR T-cell Therapy in India? 

The cost of CAR T-cell therapy in India ranges from USD 60,000 to USD 75,000. NexCAR19 is available across 18+ towns and cities in India within the same price range. Innovative cancer treatments like NexCAR19 are more affordable in India than in international markets while maintaining global standards. This pricing reflects a significant step toward making cutting-edge cancer treatment accessible to Indian patients and beyond.

What are the Potential Side Effects of NexCAR19?

NexCAR19 is one of the safest CAR T-cell therapies as it is humanized and personalized for the patient. However, a few potential side effects can occur as a response from the immune system. These effects are:

• Cytokine Release Syndrome: CRS, or cytokine release syndrome, occurs when the immune system becomes highly active. It is among the most common side effects of NexCAR19. Symptoms include fever, low blood pressure, and irregular or rapid heartbeat. CRS usually occurs within 2 to 4 weeks of infusion. 
• Neurological Events: NexCAR19 may affect the central nervous system, making patients feel confused, dizzy, agitated, or disoriented. Severe symptoms might affect speech and consciousness or cause seizures.
• Hemophagocytic Lymphocytosis (HLH): HLH is another side effect that may occur due to a highly active immune system. It can present with fever and low blood counts. Oncologists treat HLH with supportive medicines to suppress inflammation.
• Prolonged Low Blood Cell Counts (Cytopenia): Upon administration of NexCAR19, cytopenia may occur. Cytopenia is marked by low levels of one or more types of blood cells. Prolonged cytopenia may increase the risk of infection. 

What Precautionary Measures Are to be Taken Before and After the NexCAR19 Treatment?

Before receiving NexCAR19 therapy, inform your doctor about all your current and past medical issues, such as neurological problems (seizures, stroke), heart issues, lung diseases, liver and kidney problems, and infections. 

It is advised to tell your physician about all the medications you are taking, including herbal supplements, prescribed drugs, vitamins, and over-the-counter drugs. Inform them about your pregnancy status and if you are planning to be pregnant soon.

Once the doctors have found you fit for NexCAR19, they will initiate the treatment process. After the treatment is done, there are certain restrictions that patients must comply with for a healthy recovery. These include:

• Do not operate heavy machinery, drive a vehicle, or participate in intense physical activity for around eight weeks after the treatment. NexCAR19 can affect motor coordination in the short term and cause confusion, weakness, sleepiness, dizziness, and seizures.
• Do not donate blood, organs, oocytes, sperm, and other cells without consulting your physician.
• Consume meals cooked under hygienic conditions and avoid crowded places to decrease the risk of infection.
• Only start or stop any medications after consulting your hematologist or medical oncologist.
• Follow up regularly with your treating doctor as per their recommendations.
• Call your healthcare provider right away if you experience any of the following:
  • Fever (38°C or higher)
  • Dizziness or lightheadedness
  • Severe nausea, vomiting, or diarrhea
  • Irregular heartbeat
  • Difficulty breathing
  • Chills
  • Confusion
  • Severe fatigue or weakness

Interactive Session Between MediJourney Team and FMRI Doctors

Our team members were fascinated by the innovative treatment technique and asked a few questions to understand CAR T-cell therapy better.

Ques. Why does it take a few weeks for NexCAR19 to be administered? How is this different from other drugs?

Ans. NexCAR 19 is made from a patient's own T-cells. The cells are sent to a controlled laboratory, cultured, modified, and multiplied to reach a desirable dose. This takes approximately 19 days from leukapheresis.

Ques. How many days after the therapy would CRS be expected? Is it long-term?

Ans. Cytokine release syndrome is the most frequent side effect of the therapy, but it is expected within the first 4 weeks of the infusion, not long term.

Ques. How common are the serious side effects?

Ans. In clinical trials, severe symptoms were seen in 5% of patients. These side effects may depend upon several factors, including the pre-existing disease burden and your clinical condition.

Ques. How many days will patients need to follow up with their treating doctors?

Ans. After discharge, patients may be asked to follow up weekly or twice a week for the first month. The frequency of follow-up will decrease with time based on the physician's discretion. If patients achieve remission beyond 6 months, this frequency may be shortened to twice a year, but it is recommended that follow-ups continue for up to 15 years.

A Leap Forward for Cancer Treatment in India

The introduction of ImmunoACT NexCAR19 represents a major leap forward for India in immunotherapy. It positions the country as a leading player in the global fight against cancer, offering hope to countless patients while showcasing the potential of Indian research and innovation.

Conclusion

The CAR T-Cell Therapy event at FMRI, Gurgaon, not only celebrated a significant medical achievement but also set the stage for transformative cancer care in India. The collaborative efforts of scientists, oncologists, and healthcare institutions underscore the power of innovation and dedication in overcoming some of the most challenging medical conditions.

With pioneers like Mr. Sirish Arya and the team at ImmunoACT, India is poised to take charge of delivering advanced, life-saving therapies to the world. The future of cancer care has never looked brighter.