CAR-T and cell therapy clinical trials in the EU explained

What are advanced therapy medicinal products (ATMPs)?

Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells^[1]. They are a separate regulatory category in the European Union precisely because they work differently from conventional chemical drugs.

ATMPs can be classified into three main types^[1].

• Gene therapy medicines – contain genes that lead to a therapeutic, prophylactic or diagnostic effect, usually by inserting recombinant genes into the body, for example to treat genetic disorders, cancer or long-term diseases^[1].
• Somatic-cell therapy medicines – contain cells or tissues that have been manipulated to change their biological characteristics, or cells or tissues not intended to be used for the same essential functions in the body^[1].
• Tissue-engineered medicines – contain cells or tissues modified so they can be used to repair, regenerate or replace human tissue^[1].

Some ATMPs may also contain one or more medical devices as an integral part of the medicine; these are referred to as combined ATMPs, for example cells embedded in a biodegradable matrix or scaffold^[1].

CAR-T medicines sit at the intersection of gene therapy and cell therapy: they are made from a patient's own T cells that are genetically modified outside the body. In EMA documents they are described as a type of advanced therapy medicine called a 'gene therapy product'^[2].

How is CAR-T therapy made from a patient's own cells?

CAR-T therapy is a type of immunotherapy. CAR stands for chimeric antigen receptor, and the treatment is a very complex and specialist procedure that can only be given in a registered CAR-T therapy hospital, by healthcare professionals with the expertise to look after the patient^[3].

A specialist nurse collects the patient's T cells, which are then sent to the laboratory where the T cell is changed to become a CAR T-cell. After a few weeks, the patient receives a drip containing these cells back into the bloodstream, and the CAR T-cells then recognise and attack the cancer cells^[3].

The collection step is called apheresis. In the laboratory, scientists change the T cells into CAR T-cells by adding a gene that causes the cell to make proteins on its surface called chimeric antigen receptors (CARs); these CARs can recognise and target a specific protein on the surface of the cancer cells. The changed T cells then grow and multiply in the laboratory until there are enough CAR T-cells to be given back as a drip. The laboratory changes mean the CAR T-cells can stay in the body for long periods, recognising and attacking the specific cancer cells^[3].

For the authorised product Kymriah, this is described in regulatory terms as an immunocellular therapy containing tisagenlecleucel – autologous T cells genetically modified ex vivo using a lentiviral vector encoding an anti-CD19 chimeric antigen receptor (CAR)^[4].

Why can a CAR-T medicine only be given to the patient whose cells were used?

CAR-T is an autologous therapy: it is prepared using the patient's own white blood cells, which are extracted from the blood and genetically modified in the laboratory, and it must only be given to the patient whose cells were used to make it^[2]. The same rule applies to Yescarta and Carvykti^[5][6].

Because each batch is made from an individual patient's cells, the cellular composition and the final cell number vary between individual patient batches. For Kymriah, one to three infusion bags contain a total of 1.2x10⁶ to 6x10⁸ CAR-positive viable T-cells, and for paediatric and young adult patients with B-cell ALL the approved dose range is 0.2 to 5x10⁶ CAR-positive viable T-cells/kg body weight for patients up to 50 kg^[4].

Carvykti can only be given to patients by trained doctors in specialist hospitals. This restriction on where the medicine is given reflects both the complexity of the product and the need for rapid access to emergency equipment^[6].

What happens on the day of the infusion – and just before it?

Before having a CAR-T medicine, the patient should have a short course of chemotherapy to clear away their existing white blood cells^[2]. The infusion itself is a single drip into a vein^[5].

Just before the infusion, the patient is given paracetamol and an antihistamine medicine to reduce the risk of reactions to the infusion. A medicine called tocilizumab, and emergency equipment, must be available in case the patient has a potentially serious side effect called cytokine release syndrome^[2]. For Yescarta and Carvykti, a suitable alternative may be used when tocilizumab is unavailable due to a shortage^[5][6].

Which CAR-T medicines are authorised in the EU and for which blood cancers?

Three CAR-T medicines are described in EMA product information as authorised for use in the European Union: Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel) and Carvykti (ciltacabtagene autoleucel)^[2][5][6]. All three target blood cancers, which are rare diseases and were the basis for orphan medicine designations^[2].

Medicine (active substance)	Authorised indications (as described by EMA)	Target protein on cancer cells
Kymriah (tisagenlecleucel)	B-cell acute lymphoblastic leukaemia (ALL) in children and young adults up to 25 years of age whose cancer did not respond to previous treatment, came back two or more times, or came back after a stem cell transplant; diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in adults whose cancer came back or did not respond after two or more previous treatments[2]	CD19[2]
Yescarta (axicabtagene ciloleucel)	Adults with high-grade B-cell lymphoma (HGBL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL) or follicular lymphoma (FL) whose cancer has returned or stopped responding to previous treatment[5]	CD19[5]
Carvykti (ciltacabtagene autoleucel)	Adults with multiple myeloma that has come back and has not responded to treatment, who have received at least one prior therapy including an immunomodulatory agent and a proteasome inhibitor, whose disease has worsened since the last treatment, and for whom lenalidomide did not work[6]	BCMA (B cell maturation antigen)[6]

Kymriah was designated an orphan medicine for B-cell ALL on 29 April 2014, for DLBCL on 14 October 2016 and for FL on 19 July 2021^[2]. Yescarta was designated an orphan medicine for DLBCL on 16 December 2014, for PMBCL on 9 October 2015 and for FL on 11 November 2015^[5]. Carvykti was designated an orphan medicine on 28 February 2020^[6].

Other cell therapies are also authorised or in development. Cancer Research UK lists three types of CAR T-cell therapy made by different companies – tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta) and brexucabtagene autoleucel (Tecartus). Outside haematology, the European Society for Blood and Marrow Transplantation (EBMT) collects information on the different types of transplants and cellular therapies happening in Europe, including CAR T-cell therapies. Its latest report showed that in 2021 around 2,500 people had CAR T-cell therapy^[3].

What do the clinical trial results for authorised CAR-T medicines show?

Regulatory assessments of CAR-T medicines report results from studies in specific patient groups, and these numbers are tied to the population studied. They do not predict what will happen in an individual patient.

In the main study of Kymriah in B-cell ALL, which involved 92 children and young adults aged 3–25 years whose cancer had come back after previous treatment or did not respond to treatment, around 66% of patients had a complete response (no signs of the cancer left) in the 3 months after treatment. Twelve months after treatment, the likelihood of survival was 70%^[2].

In the main study of Kymriah in DLBCL, which involved 165 patients with at least 2 previous treatments who could not have a stem cell transplant, around 24% of patients had a complete response and 34% had at least a partial response after at least 3 months. Twelve months after treatment, the likelihood of survival was 40%. In the main study of Kymriah in FL, which involved 98 patients whose cancer had come back after previous treatment or did not respond to treatment, around 69% of patients had a complete response 3 months after treatment^[2].

In the main study of Yescarta involving 359 patients with HGBL or DLBCL that had not responded to, or returned within a year of receiving, one previous treatment, patients given Yescarta were event-free for around 8 months on average, compared with 2 months for patients given standard cancer treatments. After 24 months, 41% of patients given Yescarta were event-free, compared with 16% of patients receiving standard treatment^[5].

In a main study of Carvykti in multiple myeloma that had returned and did not respond to three or more previous treatments, after one and a half years about 84% of patients (95 out of 113) responded to the treatment and 69% (78 out of 113) had signs that the cancer had disappeared; Carvykti was not compared to another medicine in this study. A second study showed that after nearly 16 months of treatment, fewer patients who received Carvykti had their disease worsen (31%, 65 out of 208) compared with patients who received standard treatment alone (58%, 122 out of 211 patients)^[6].

What side effects are monitored after a CAR-T infusion, and for how long?

Serious side effects occur in most patients treated with Kymriah. The most common serious side effects are cytokine release syndrome and decreases in platelets, haemoglobin or white blood cells^[2].

Cytokine release syndrome is a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure. This is why tocilizumab and emergency equipment must be available during treatment^[2].

The monitoring periods differ slightly between products. After Kymriah or Yescarta, patients should be closely monitored for 10 days after treatment for side effects and are advised to stay close to a specialist hospital for at least 4 weeks after treatment^[2][5]. After Carvykti, patients should be closely monitored for side effects daily for 14 days after the infusion and then periodically for an additional two weeks, and are advised to stay close to a specialist hospital for at least four weeks after the infusion^[6].

The most common side effects with Carvykti, which may affect more than 1 in 5 people, include neutropenia (low levels of neutrophils), fever and lymphopenia^[6].

How do you find a CAR-T or cell therapy clinical trial you could join?

People with types of cancer other than those covered by authorised CAR-T indications might have CAR T-cell therapy as part of a clinical trial. For authorised treatments, the doctor treating you can tell you more about where you will be treated, because the therapy can only be given in a registered CAR-T therapy hospital^[3].

When looking for a study, check whether it is registered and authorised in the EU and whether the provider can confirm approval. Trials recruiting in Europe can also be searched on clinicaltrials.eu.

In the EU, the Committee for Advanced Therapies (CAT) of the EMA, together with the Heads of Medicines Agencies (HMA), has published statements on the risks of unregulated advanced therapies, including practical advice for patients and caregivers on how to identify them^[1].

How can you recognise an unregulated advanced therapy?

Unregulated advanced therapies may put patients at risk, causing serious side effects without any proven benefits. These products are often sold on websites or through social media channels as a last hope, exploiting the worries of patients and their families^[1].

Authorities are clamping down on those supplying unregulated ATMPs and encourage patients and caregivers to report suspicious cases to their national authorities. The EMA and HMA published a joint statement in March 2025 following reports of providers offering unregulated dendritic cell therapies for cancer treatments in the EU^[1].

Warning signs that an advanced therapy may be unregulated and illegally supplied include^[1]:

• Providers market the product as experimental but use it outside an authorised clinical trial^[1];
• Providers cannot confirm that the product has been approved by the EMA or for use by a national authority^[1];
• Claims of benefits exceed those of approved treatments (if available) without supporting medical literature^[1].

If you or a family member has been offered an advanced therapy, contact your national competent authority to verify its approval. Be cautious with treatments promoted online or through social media, and always seek a second opinion before proceeding. EMA's Committee for Advanced Therapies issued a similar statement in April 2020 warning against using unproven cell-based therapies^[1].

How are cell and gene therapies assessed and authorised in the EU?

In the European Union, ATMPs follow a dedicated regulatory framework with specific legal requirements for advanced therapies, and companies researching, developing and manufacturing them receive guidance and support during the product lifecycle^[1].

The Committee for Advanced Therapies (CAT) is the EMA committee specifically concerned with advanced therapies, and it works alongside the Heads of Medicines Agencies (HMA) on safety communications, including joint statements on unregulated advanced therapies^[1]. Marketing authorisations for advanced therapies are granted at EU level; the product pages for Kymriah, Yescarta and Carvykti each state that the medicine is authorised for use in the European Union^[2][5][6].

Once a medicine is authorised, further studies may still be requested. For Kymriah, the marketing authorisation holder submitted the final study results from a completed phase IIIb paediatric clinical study in accordance with Article 46 of Regulation (EC) No 1901/2006, and these data were also submitted as part of a post-authorisation measure for that study. The assessment report for that procedure was adopted by the CHMP (Committee for Medicinal Products for Human Use)^[4].

When should you seek advice from your doctor or treatment centre?

CAR-T therapy can only be given in a registered CAR-T therapy hospital, so the treating doctor is the person who can confirm whether you are eligible and where you would be treated. Cancer Research UK notes that, in England and Wales, a National CAR T Clinical Panel (NCCP) discusses which patients can receive CAR T-cell therapy, so access decisions may involve a panel rather than a single clinician^[3].

After treatment, you should stay close to the specialist hospital for at least four weeks^[6]. Report fever, vomiting, shortness of breath, pain or low blood pressure promptly, because these can be signs of cytokine release syndrome^[2].

If you have been offered an advanced therapy outside an authorised clinical trial, contact your national competent authority to verify its approval before proceeding^[1].

Summary

Check the product name and its EMA authorisation before agreeing to any cell or gene therapy, and confirm that the treatment will take place in a registered CAR-T therapy hospital^[3].

Plan for the monitoring period that follows the infusion – 10 days for Kymriah and Yescarta, and 14 days plus a further two weeks for Carvykti – and keep yourself within reach of the specialist centre for at least four weeks^[2][5][6].

Ask for the study details when a therapy is offered as part of research, and be cautious about products sold online or through social media as a last hope^[1].

This article is for information only and does not replace medical advice. Discuss any treatment decision with your doctor or specialist centre.

1. [1] Advanced therapy medicinal products: Overview (accessed 2 June 2026) — https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-products-overview
2. [2] Kymriah (accessed 2 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/kymriah
3. [3] CAR T-cell therapy (accessed 2 June 2026) — https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/CAR-T-cell-therapy
4. [4] Assessment report for paediatric studies submitted according to Article 46 of Regulation (EC) No 1901/2006 – Kymriah, tisagenlecleucel (accessed 2 June 2026) — https://www.ema.europa.eu/en/documents/variation-report/kymriah-h-c-4090-p46-012-epar-assessment-report_en.pdf
5. [5] Yescarta (accessed 2 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta
6. [6] Carvykti (accessed 2 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/carvykti