Question 1

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

Dr. Akash Khandelwal · Accepted Answer

The cutoff is 5 million CAR-T cells required per kilogram of the patient's body weight.

Question 2

For the approved indications of relapsed or refractory diffuse large B-cell lymphoma and B-cell ALL, patients need to be over 15 years old. What is the name of the CAR-T product available in India, so I can look up the clinical trial research myself?

Dr. Akash Khandelwal · Accepted Answer

There are two CAR-T products commercially available in India right now, both targeting CD19. One is NexCAR19, made by ImmunoACT, which has been commercially available in India since December 2023, so there is more than a year of experience with it. The second product was launched only about a month back and is still underutilised. Both target CD19, the marker responsible for the B-cell response, so B-cell ALL and B-cell lymphoma are the appropriate targets, not Burkitt lymphoma (the CAR-T construct needed is different) or CNS lymphoma (which does not respond as well).

Question 3

I also attend a gene and cell therapy conference in Vietnam, and my institution is developing its own academic clinical trial in CAR-T. Are there upcoming CAR-T trial opportunities in India that international patients could join?

Dr. Akash Khandelwal · Accepted Answer

Fortis Shalimar Bagh is in talks to run its own CD19-directed CAR-T clinical trial for lymphoma and leukemia. Myeloma CAR-T trials are also upcoming from other companies and should be commercially available in India by year end. However, international patients cannot be enrolled in Phase 1 or Phase 2 trials, since these require longer follow-up before DCGI grants approval based on long-term data for commercial or international use. Until then, the CD19 CAR-T that is already commercially available is the only option for international patients.

Question 4

Do you have specific nutritional considerations for patients undergoing CAR-T cell therapy, especially in a setting with very limited access to CAR-T treatment centres?

Dr. Akash Khandelwal · Accepted Answer

Adequate T-cell collection is the rate-limiting step for CAR-T, and nutrition can affect that. If enough T-cells aren't collected, the only option is to wait and reattempt collection after about 6 months. Beyond that, nutrition doesn't play a major role, since the chemotherapy used for CAR-T is not very toxic and even a frail patient can undergo CAR-T therapy. Nutrition plays a bigger role in bone marrow transplants than it does in CAR-T cell therapy.

Question 5

Can you elaborate further on the vein-to-vein time you mentioned, around 19 days: how exactly are the cells collected and processed before the transplant?

Dr. Akash Khandelwal · Accepted Answer

T-cells are collected the same way a stem cell or single-donor platelets are collected, through an apheresis machine. No drugs are given before collection; a vein is all that's needed, and if an adequate number of T-cells is found, CAR-T manufacturing can go ahead.

Question 6

Is there any risk to hair regrowth after the chemotherapy and CAR-T treatment?

Dr. Akash Khandelwal · Accepted Answer

The conditioning chemotherapy is just cyclophosphamide and fludarabine, which can cause cytopenias and neutropenia, but this is manageable since the dosing isn't very high, so fitness is not usually a major factor. It's the CAR-T related side effects that vary more from patient to patient. If the disease is well controlled going in, complications are less likely, but even with good control, side effects such as cytokine release syndrome or, less commonly, ICANS (which can affect the brain) can occur. Whatever side effects arise are manageable and not life-threatening: no deaths from CAR-T related side effects have been seen, and it isn't well documented even in the long-term data.

Question 7

What are the specific cancer cells targeted by CAR-T, and can it be applied to ovarian or cervical cancers?

Dr. Akash Khandelwal · Accepted Answer

Not yet - it hasn't shown good promise there so far. Currently CAR-T is only available for B-cells, targeting CD19, and this has shown long-term responses based on research done in the US, with a large subset of patients still in remission after CD19-targeted CAR-T infusion. Other categories are in development too, such as dual-target CARs and attachments that help CAR-T expand and persist for longer, but currently only CD19 CAR-T can be offered, since that's what's commercially available in India.

Question 8

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.

Question 9

If possible, could you share your slides with us so we can go through the presentation again?

Dr. Akash Khandelwal · Accepted Answer

Yes, no problem: the slides will be shared after the session.

CAR-T Cell Therapy

Questions Doctors Asked Dr. Akash Khandelwal