Who Is Eligible for CAR-T Cell Therapy? Outcomes and Access

Eligibility for CAR-T cell therapy is narrow and precisely defined. In India it is approved for patients aged 15 and over with relapsed or refractory B-cell lymphoma, or relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL). Refractory means the disease has not responded to treatment. Patients who have relapsed after a bone marrow transplant, or are unfit for one, are the groups for whom conventional treatment has least to offer.

CAR-T is not a general cancer treatment yet, and the patients who benefit most are often the ones with the fewest alternatives. For referring clinicians, the questions that matter are concrete: which patients qualify, which do not, what results are realistic, and how a patient actually reaches treatment. Dr. Akash Khandelwal, Consultant Hemato-Oncology & BMT, Fortis Hospital, Shalimar Bagh, New Delhi, India, addressed each of them. How the therapy works is explained in CAR-T cell therapy: a complete guide.

CAR-T cell therapy eligibility: the approved indications

At the time of his session, CAR-T in India was approved for patients aged 15 years and above in two disease settings: relapsed or refractory B-cell lymphoma and relapsed or refractory B-ALL. Dr. Khandelwal is careful to call eligibility an evolving topic. More trials are under way, and he expects further approved indications over the coming months and years.

CAR-T for relapsed or refractory B-cell lymphoma

The first indication is B-cell lymphoma that has relapsed or has not responded to treatment. Dr. Khandelwal lists the subtypes this covers:

• Diffuse large B-cell lymphoma
• Follicular lymphoma
• Mantle cell lymphoma
• Marginal zone lymphoma

CAR-T for relapsed or refractory B-cell acute lymphoblastic leukaemia

The second indication is B-cell acute lymphoblastic leukaemia (B-ALL) that has relapsed or proved refractory.

CAR-T after a failed or unsuitable bone marrow transplant

Within both indications, two groups stand out because conventional medicine has the least to offer them:

• Patients who have relapsed after a bone marrow transplant. Having already been through the most intensive treatment available, these patients have historically had few remaining options.
• Patients unfit for a bone marrow transplant. For a patient whose relapsed disease would ordinarily call for a transplant they cannot tolerate, CAR-T offers a route to potential cure that does not depend on transplant fitness.

Dr. Khandelwal describes CAR-T for these patients as a ray of hope for people who would otherwise be on palliative care, and a potentially life-changing option with a good chance of cure.

Who is not eligible for CAR-T today?

Patients under 15, patients with cancers outside the B-cell lineage and patients with Burkitt lymphoma are not candidates today. The age threshold is the first boundary: the current approval in India starts at 15 years. In the United States and Europe, a CD19 CAR-T product is approved for children and young adults up to 25 years of age with relapsed or refractory B-cell acute lymphoblastic leukaemia.

The second boundary is biological. The products Dr. Khandelwal uses all target CD19, so the disease has to be a B-cell cancer the current construct can attack. Within that group there are notable exceptions:

• Burkitt lymphoma. In Dr. Khandelwal's view, CAR-T will fail here, because the construct it would need is very different. Burkitt lymphoma cells do carry CD19, but the disease is not among the approved indications of the major CD19 CAR-T products, and published experience of CAR-T in it is limited.
• Central nervous system lymphoma. CAR-T can be tried, but in Dr. Khandelwal's experience CNS lymphomas do not do as well as other lymphomas.
• Cancers outside the B-cell lineage, including solid tumours such as ovarian or cervical cancer, for which CAR-T has not yet shown good promise. The pipeline for these cancers is described in the complete guide linked above.

Can frail patients have CAR-T?

In Dr. Khandelwal's view, even a frail patient can undergo CAR-T. One common assumption is that a patient too weak for a transplant will also be too weak for CAR-T, but the chemotherapy that accompanies CAR-T is not intensive and carries limited toxicity. Candidates are still assessed for performance status and organ function before CAR-T. Nutrition and cachexia weigh more heavily in transplant decisions. The point where a patient's condition does matter is T-cell collection, and that hurdle is set out in the CAR-T cell therapy timeline from collection to recovery.

CAR-T cell therapy success rate: long-term relapse-free survival

Dr. Khandelwal puts long-term relapse-free survival after CAR-T at about 40% in relapsed or refractory B-cell lymphoma. In relapsed or refractory B-cell acute lymphoblastic leukaemia, roughly half of patients remain relapse-free at three years in the pivotal trials. He does not oversell the outcomes: long-term response, he says, is not 100%.

These numbers need to be read against the population they describe. These are patients with bad-subset disease: cancers that were not cured by chemotherapy, or that came back after a transplant. For that group, Dr. Khandelwal considers these good numbers, and a marked improvement over standard of care. Patients who previously had no realistic hope now have a meaningful chance of long-term survival.

Why do some patients relapse after CAR-T?

When CAR-T fails over the longer term, the cause is usually one of two things. The CAR-T cells do not remain in the body for long enough, or the cancer develops resistance to them. Research on keeping CAR-T cells expanding after infusion is aimed squarely at these failures, and Dr. Khandelwal expects better answers over time on how to maintain responses after treatment.

Case study: CAR-T for a transplant-unfit patient from Europe

Dr. Khandelwal has treated a number of patients with CAR-T at Fortis Shalimar Bagh, with more in process at the time of the session. One case illustrates exactly the patient the therapy is designed for.

The patient, a man from a European country, had splenic marginal zone lymphoma that had progressed. He had been deemed unfit for an autologous transplant, and his home health system had nothing further to offer him. He researched his options himself, contacted Dr. Khandelwal and the team directly, and travelled for CAR-T.

He was discharged successfully and is now living well. Dr. Khandelwal describes the change in plain terms: a man who had no hope now has something to look forward to in his life. The case brings together the indications above in a single patient: a relapsed B-cell lymphoma subtype on the approved list, transplant ineligibility, and no remaining standard option.

CAR-T in India: products, availability and cost for international patients

Which CAR-T products are available in India?

Two CAR-T products were available at the time of the session, and both target CD19, as Dr. Khandelwal explained in the masterclass Live Discussion. The first, NexCAR19 (actalycabtagene autoleucel), developed by ImmunoACT, has, according to Dr. Khandelwal, been commercially available since December 2023, which means more than a year of commercial use and, in Dr. Khandelwal's words, plenty of experience with it. This is the product his team has used. The second, from Immuneel Therapeutics, had been launched only about a month before the session and was still underused.

CAR-T cost in India

Dr. Khandelwal describes the Indian CAR-T as one of the most affordable CAR-T therapies in the world. It is still manufactured individually for each patient, however, and so still comes with a significant cost.

Can international patients join a CAR-T clinical trial?

A clinical trial is not a practical route to newer CAR-T products for patients from abroad. Fortis Shalimar Bagh is itself working towards a CAR-T trial, but Dr. Khandelwal is clear about the constraint. Early-phase (phase 1 and phase 2) trials of newer products require longer follow-up, and until a product receives approval from the Drugs Controller General of India on the strength of long-term data, it cannot be used commercially for patients or offered to people from abroad. Until then, the commercially available CD19 CAR-T is the realistic option for international patients.

When to refer for CAR-T: a checklist for doctors

For a doctor considering referral, Dr. Khandelwal's material reduces to a short checklist:

1. Confirm the diagnosis and status: a B-cell lymphoma subtype on the approved list or B-ALL, relapsed or refractory, in a patient aged 15 or older (the current threshold for the products available in India).
2. Note the transplant history: relapse after bone marrow transplant, or unfitness for one, strengthens the case for CAR-T.
3. Rule out the poor fits: Burkitt lymphoma, and weigh the weaker results in CNS lymphoma.
4. Do not exclude a patient for frailty alone, but recognise that an adequate T-cell collection is essential.
5. Plan for at least two months of treatment time away from home.

Dr. Khandelwal also invites colleagues to discuss individual patients with him directly, an approach that suits a therapy whose approved indications he expects to widen over the coming months and years.