Question 1

How many CAR-T cells are required per kilogram of body weight?

Dr. Akash Khandelwal · Accepted Answer

The cut-off is 5 million: we require 5 million CAR-T cells per kilogram of body weight.

Question 2

The approved indications include relapsed or refractory large B-cell lymphoma and B-cell ALL in patients over 15 years old. What is the name of the CAR-T product available in India, so I can look up its clinical trials?

Dr. Akash Khandelwal · Accepted Answer

Two CAR-T products are available in India right now, both targeting CD19. One is NexCAR19 by ImmunoACT, which we have used so far; it has been commercially available in India since December 2023, so there is more than a year of commercial use and plenty of experience with it. The other, by Immuneel, was launched just a month back and is still underutilised. CD19 is the marker on B cells, so B-cell ALL and B-cell lymphoma are the appropriate targets. Burkitt lymphoma also carries CD19, but CAR-T fails there because the construct would have to be very different, so it is not an indication. CNS lymphomas unfortunately do not do as well as other lymphomas, although CAR-T can be tried.

Question 3

Are there specific nutritional considerations for patients undergoing CAR-T cell therapy, especially where there are very few CAR-T centres?

Dr. Akash Khandelwal · Accepted Answer

Yes, if poor nutrition is present it will always play a role, because you may not get the desired T cells. Adequate T-cell collection is the cut-off and the rate-limiting step for CAR-T: if adequate T cells are not collected, nothing can be done except to wait and make a second collection attempt after 6 months. Beyond that, I do not see nutrition playing a role, because the chemotherapy used for CAR-T does not carry much toxicity, and even a frail patient can undergo CAR-T. Cachexia plays a role more in transplants than in CAR-T, and even there nutrition is one factor among many (the type of transplant, the chemotherapy, whether the transplant can be delayed) rather than the defining one.

Question 4

Which specific cancer cells does CAR-T target, and can it be applied to ovarian or cervical cancers?

Dr. Akash Khandelwal · Accepted Answer

Not yet; it has not yet shown good promise there. Currently CAR-T in India is available only for B cells, targeting CD19. CD19-targeted CAR-T has shown long-term responses in research from the US, with a large subset of patients still in remission after infusion. CAR-T has many categories and generations: CD19 is a single-target CAR, and there are dual-target CARs and attachments that make CAR-T expansion and long-term persistence easier. Various cells are being targeted every day as potential CAR-T therapies, but currently only CD19 CAR-T can be offered, because that is what is commercially available in India.

Question 5

You mentioned a vein-to-vein time of around 19 days. How exactly are the cells collected and processed before infusion?

Dr. Akash Khandelwal · Accepted Answer

T cells are collected the same way stem cells or single-donor platelets are collected, through an apheresis machine. It is very basic: no drugs are given before collection. You just need a vein, and if the appropriate number of T cells is collected, you can go ahead with CAR-T manufacturing.

Question 6

After the chemotherapy and CAR-T treatment, is there any risk regarding regeneration of the hair cells?

Dr. Akash Khandelwal · Accepted Answer

The chemotherapy is just cyclophosphamide and fludarabine, which can cause cytopenias and neutropenia, but this is manageable because the dosing is not that high, so fitness may not play a role here. It is the CAR-T-related side effects that vary from patient to patient. If the disease is well controlled, you do not expect many complications, but this is variable: even with the best control, patients can have unique complications such as cytokine release syndrome, or, less commonly, ICANS (immune effector cell-associated neurotoxicity syndrome), which can affect the brain. Most side effects are manageable, but severe cytokine release syndrome, ICANS and infections can be life-threatening in a small proportion of patients. I have not seen any deaths from CAR-T-associated side effects in my own practice.

Question 7

Where do you see CAR-T cell therapy heading in other cancers?

Dr. Akash Khandelwal · Accepted Answer

CAR-T cells are likely to become a first-line option in almost all cancers within the next 5 to 10 years. If it doesn't get there, that would actually be a missed opportunity, because it targets cells in a very different and unique way. More and more data is showing increasing promise for the treatment.

Live Discussion with Dr. Akash Khandelwal