CAR T-Cell Therapy Treatment

Who needs CAR T-Cell Therapy?

Children and young adults 

• This segment of patients requires CAR T-cell therapy because they suffer from B-cell lymphoblastic leukemia.
• Their treatment requirement is efficient because the disease can be refractory, which means that they are resistant to treatment. 
• They can also relapse, which can come back even after remission. 
• The FDA has approved CAR T-cell therapy for this group under particular criteria. 

Adults who have been facing Non-Hodgkin Lymphoma

It is also known as Diffuse Large B-Cell Lymphoma, primarily mediastinal. It is usually considered after two or more failed therapies.

Patients who are suffering from Multiple Myeloma

• People who have optimised and applied other primary drug classes like Proteasome inhibitors, monoclonal antibodies, or immunomodulatory drugs. 
• Some candidates also need to meet specific criteria. For example, they should have adequate organ function, like the heart, kidneys, or liver. 
• There should not be any active infections or unmanageable medical issues. 
• Patients often undergo treatment at a specialized centre certified to administer CAR T-Cell therapy. 
• It is for those patients who have aggressive treatment-resistant blood cancer and also have a good health status, and can undergo intensive personalised immunotherapy procedures. 

Types of CAR T-Cell Therapy 

• ABECMA - Adult patients with refractory or relapsed multiple myeloma include an immunomodulatory agent, a Proteasome inhibitor, and a non-CD38 monoclonal antibody. 
• BREYANZI - For adult patients facing refractory large B-cell lymphoma after two or more stages of systemic treatment. It also applies to adult patients receiving refractory follicular lymphoma after two or more stages of systemic therapy. 
• CARVYKTI - It is also applicable for adult patients suffering from refractory multiple myeloma and have received at least one prior stage of therapy, including a Proteasome inhibitor and any immunomodulatory agent. 
• KYMRIAH - Refractory lymphoma after two or more stages of systemic therapy, including diffuse large B-cell Lymphoma. For adult patients with similar problems, this therapy is applicable. 

There are several emerging CAR T-Cell therapies still in clinical trials, i.e., CD22,  CD123, GD2, etc. 

Pre-therapy evaluation and diagnostics 

Pre-therapy evaluation and diagnostics are vital because they can help determine patient eligibility and safety insurance, while optimizing the treatment outcome. This process usually happens at a specialised CAR T-Cell treatment centre, which involves various steps across the laboratory and medical sections. 

Assessment of the disease 

• The first step is confirming the type and stage of the cancer and documenting the treatment history. 
• Pathology and biopsy diagnosis are verified, and antigen expressions are then targeted. 
• For flow cytometry or immunohistochemistry, the pressure of the target antigen on the cancer cells is confirmed. 
• Tumor burden is assessed through MRI, PET-CT, and CT scan. 
• Bone marrow biopsy is done to identify Leukemia and Lymphoma. 

Evaluation of the laboratory domain 

• Here, certain organ functions are examined and risk factors are detected. 
• It includes liver function tests, kidney function, uric acid, and LDH, helping with tumour identification, complete blood count, and kidney function. 

Functional and Organ Testing 

• To evaluate the health of the patient and identify important contraindications, it is essential to conduct a MUGA scan. 
• It helps examine neurological conditions, identify the status of the patient's performance, and run pulmonary function tests as well.
• CAR T-Cell therapy also requires intensive monitoring and support, meaning there should be availability during and after the infusion. 
  

Procedure Planning 

The planning process of CAR T-Cell therapy is a multi-stage process that requires cooperation and coordination among medical teams, certified laboratories, caregivers, and the patient. It typically ranges from several weeks from the first evaluation to the post-infusion supervising as well. 

Pre-treatment assessment and clearance 

• It confirms eligibility and prepares for safe treatment. 
• It conducts full pre-therapy diagnostics with a multidisciplinary team, obtains informed consent from the patient, and coordinates with the insurance and counselling of financial conditions. It also builds a proper support system. 

Leukapheresis

• It is also called T cell collection, and it requires approximately one day. 
• The patient witnesses leukapheresis, which is a blood-straining process for collecting T cells. It requires effective vein access that can take 3 to 6 hours. 

T-cell engineering 

• The timeline is between 2-5 weeks. 
• It has collected T-cells recently from a certain lab. T-cells are mainly engineered to express clonal antigen receptors. 

Post-infusion supervising 

• It has a timeline of at least 7 to 30 days. 
• Impatient observation can require around 7 to 14 days, based on the risk. 
• It can monitor Cytokine release syndrome and neurotoxicity. 

Risks and Potential Complications of CAR T-Cell Therapy

This therapy is a highly effective and life-saving treatment that poses essential risks and unavoidable complications. These complications and risks can be life-threatening as well, and some of them are discussed further.

Cytokine Release Syndrome 

• It is intense as it creates a reaction with the body releasing an amount of cytokinins, which are inflammatory proteins, in response to the activation of this therapy. 
• The symptoms of the syndrome are the patient suffering from high fever, low blood pressure, difficulty breathing, fast heart rate, and dysfunction of the organs, like the kidneys or liver.  
• It mainly occurs within 1 to 14 days after the initiation and can be managed with 1 to 6 inhibitors of Tocilizumab, steroids for severe cases, along with IV fluids, oxygen, and also ICU support as per requirements. 

Neurotoxicity 

• This means that the patient is witnessing neurological side effects because of immune activation, which are affecting the brain. 
• The primary symptoms of this potential complication are that the patient is having severe confusion and disorientation. 
• It may also mean that they are facing difficulties speaking or writing, frequent seizures, hallucinations, and in some cases, they can also slip into a coma. 

Infections

• Before infusion, lymphodepletion weakens the immune system of the patient. CAR T-cells can destroy normal cells by minimizing the production of antibodies. 
• It causes certain common infections like fungal, viral, and bacterial, and can be managed with Prophylactic microbials. 

Apart from these biological challenges, it can cause psychological and cognitive impacts like anxiety or PTSD. There is a possibility of the occurrence of long-term cognitive alterations if neurotoxicity occurs. 

Recovery After CAR T-Cell Therapy and Long-Term Care 

Post-recovery and long-term care after the application of this therapy are extremely important because they ensure the health of the patient, along with managing the side effects and monitoring the relapse of the cancer. 

Post-Recovery Phase

• Cytokine release syndrome and neurotoxicity can linger in the immediate recovery phase. 
• It can close follow-up visits, especially every week for the first 2 months. 
• Blood count monitoring and tracking the liver and kidney functions for infections, and imaging, are important to examine the responses of patients. 
• It also looks after the prevention of infections from the therapy by maintaining strict hygiene and infection control measures. 

Long-term plan

• Cancer monitoring, recovery of the immune system, and neurological cognitive elements, along with psychological support, should be key focus areas. 
• The re-vaccination schedule needs to be considered along with followers of the endocrine system and fertility counselling. 

Success Rate of CAR T-Cell Therapy in India 

In Indian clinical trials, this therapy has shown a success rate of 73% among blood cancer patients, especially B-cell lymphoma and leukemia. The Lancet Haematology has published this report that highlighted potential aspects for the patients from the therapy. 

Why Choose India for CAR T-Cell Therapy 

• The reason that India is a promising choice for CAR T-cell therapy is due to the high success rate of new technologies. 
• Bombay IIT, Tata Memorial Centre, and ImmunoACT have developed NexCAR19. In clinical trials, a 73% response rate was observed among leukaemia and lymphoma patients with a significant reduction of the tumour. 
• Varnimcabtagene autocel is the second approved CAR T-cell therapy in India. It is developed by Immuneel Therapeutic in coordination with Hospital Clinic de Barcelona. The imaging trial offered around 83.3% in terms of the overall response rate, with more effective treatment of lymphoma patients.
• India offers comparatively affordable treatments than several other countries. 
• India has a good medical tourism infrastructure and support. 

Required Documents for Patients Traveling to India for CAR T-Cell Therapy

For international patients planning to undergo CAR T-Cell therapy in India, certain documents are required to ensure a hassle-free medical trip. These include:

• Valid Passport: Must be valid for at least six months from the date of travel.
• Medical Visa (M Visa): Issued by the Indian Embassy/Consulate based on medical necessity.
• Invitation Letter from Indian Hospital: A confirmation from the hospital outlining the treatment plan and duration.
• Recent Medical Records: Including X-rays, MRIs, blood reports, and a doctor’s referral from the home country.
• Completed Visa Application Form: Along with passport-size photographs as per specifications.
• Proof of Financial Means: Recent bank statements or health insurance coverage.
• Medical Attendant Visa: Required for a companion or caretaker traveling with the patient.

It's recommended to consult the Indian consulate or your medical facilitator for updated guidelines and assistance with documentation.

Top CAR T-Cell Therapists in India

Here is a look at some of the leading therapists for CAR T-Cell procedures in India: 

1. Dr. Vinod Raina, Fortis Memorial Research Hospital, Gurugram
2. Dr. Sanjay Chandrasekar, Apollo Hospital, Chennai 
3. Dr. Satish Rao, SL Raheja Hospital, Mumbai
4. Dr. Indranil Ghosh, Apollo Gleneagles Hospital, Pune
5. Dr. Pawan Kumar Singh, BLK-Max Hospital, Kochi

Best hospitals for CAR T-Cell Therapy in India

Here are some of the top hospitals for this treatment in India: 

1. Fortis Hospital, Delhi
2. Nanavati Max Super Specialty Hospital, Mumbai
3. Apollomedics Super Specialty Hospital, Lucknow
4. Yashoda Hospital Secunderabad, Hyderabad
5. CMRI Hospital, Kolkata

Frequently Asked Questions (FAQs)

What types of cancer can be treated with this therapy?

B-cell Lymphoma and leukemia, Mantle cell lymphoma, Follicular lymphoma, and Multiple myeloma can be treated with this therapy. 

Is CAR T-Cell Therapy an effective cancer treatment? 

It is not a guaranteed cure, but it has long-term remission for the patients. 

How successful is CAR T-Cell therapy? 

This treatment generally has a high chance of success, with about 90% of patients positively responding to the same. 

How long does CAR T-Cell therapy last? 

For most people, it can be a one-time treatment, and the T-cells remain in the body for several months and years at a stretch. In some cases, the T-cells may go away swiftly as well. 

What happens if CAR T-Cell therapy fails? 

In case this treatment fails, there is a chance that the cancer will not respond properly to treatment. It may also lead to future recurrence. Alternative treatment options will then be explored by the doctors as per the patient’s specific circumstances.