CAR-T Cell Therapy

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).

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.

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.

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.

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.

CAR-T cell therapy re-engineers a patient's own T-cells in a lab to carry a chimeric antigen receptor that targets CD19, a marker on B-cells, so the cells can find and destroy cancer cells once returned to the body.

The vein-to-vein time, from T-cell collection to a ready-to-infuse product, is about 19 days. Including pre-infusion chemotherapy and post-infusion hospital monitoring, the complete process takes a realistic minimum of around two months.

Patients aged 15 and above with relapsed or refractory B-cell lymphoma (marginal zone, follicular, mantle cell or diffuse large B-cell) or relapsed or refractory B-cell acute lymphoblastic leukaemia, including those who have relapsed after or are unfit for a bone marrow transplant.

Yes. Two CD19-targeted CAR-T products are commercially available in India, one of them, NexCAR19, available since December 2023, with a second product launched more recently.