Cell therapies in leukaemia and lymphoma: how trials work

What are cell therapies and where do they sit in the rules?

Cell therapies for leukaemia and lymphoma belong to a regulatory group called advanced therapy medicinal products (ATMPs) – medicines for human use that are based on genes, tissues or cells. ATMPs are classified into three main types: gene therapy medicines, somatic-cell therapy medicines and tissue-engineered medicines; some ATMPs also contain one or more medical devices as an integral part of the medicine and are called combined ATMPs^[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; they can be used to cure, diagnose or prevent diseases^[1]. CAR-T products used in leukaemia and lymphoma sit in this category – they are made from your own cells, modified outside the body and given back to you. The same boundary matters beyond Europe: only a few cell-based immunotherapies have gained FDA approval, while the majority remain in the context of investigator-initiated trials (IITs), where academically oriented transfusion centres can play an important role^[2].

The authorised products themselves are approved centrally in the European Union, which is why their public assessment information is published by the European Medicines Agency (EMA) rather than by a single country's authority^[3][4]. For a patient or caregiver, the practical consequence is simple: an authorised cell therapy has a public assessment report describing exactly which patients it was studied in and what was measured.

Which CAR-T cell therapies for leukaemia and lymphoma are authorised in the EU?

Two examples show how narrow the authorised indications are. Tecartus (brexucabtagene autoleucel) is authorised for adults with mantle cell lymphoma whose cancer has come back after two or more previous treatments, including a Bruton's tyrosine kinase (BTK) inhibitor, and for adults 26 years of age and older with acute lymphoblastic leukaemia whose cancer has come back or did not respond to previous treatments. Both B-cell cancers are rare, and the product was designated an orphan medicine – for mantle cell lymphoma on 13 November 2019 and for acute lymphoblastic leukaemia on 19 October 2020^[3]. Authorisation of a third anti-CD19 product, lisocabtagene maraleucel, was already expected in 2020, which shows how quickly this small list has grown^[5].

Breyanzi (lisocabtagene maraleucel) is authorised in adults for diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL). In DLBCL, HGBCL, PMBCL and FL grade 3B it is used when the cancer came back within 12 months of finishing chemoimmunotherapy, or did not respond to the first round of chemoimmunotherapy; in relapsed or refractory DLBCL, PMBCL, FL3B or FL it can also be used after two or more previous treatments with systemic therapy. In adults with MCL it is used when the cancer has come back or did not respond after at least two systemic therapies including a BTK inhibitor. These indications are not an accident of commercial choice: they track the populations in which the benefits were measured, and the eligibility rules of a trial or an authorised label are the same kind of filter applied to a real patient^[4].

Product	Active substance	Authorised patient group	Number of prior treatments required
Tecartus[3]	brexucabtagene autoleucel	Adults with mantle cell lymphoma; adults 26 years and older with acute lymphoblastic leukaemia	MCL: two or more, including a BTK inhibitor; ALL: relapsed or not responding to previous treatments
Breyanzi[4]	lisocabtagene maraleucel	Adults with DLBCL, HGBCL, PMBCL, FL, MCL	DLBCL/HGBCL/PMBCL/FL3B: relapsed within 12 months or refractory to first-line chemoimmunotherapy; also two or more prior systemic therapies in RR DLBCL, PMBCL, FL3B, FL; MCL: at least two systemic therapies including a BTK inhibitor

How does a CAR-T cell therapy actually work?

Tecartus contains the patient's own T cells – a type of white blood cell – which have been genetically modified in the laboratory so that they make a protein called chimeric antigen receptor (CAR). The CAR helps the T cells attach to a protein on the cancer cells called CD19; once infused, the modified T cells attach to and kill the cancer cells, helping to clear the cancer from the body^[3]. Because the target is a protein on the cell surface rather than a single cancer type, the same mechanism can be applied across several B-cell diagnoses – which is exactly what the Breyanzi indications show^[4].

Breyanzi works through the same CD19 target but is a combination of two types of genetically modified white blood cells – CD4+ T cells and CD8+ T cells collected from the patient. These cells are modified in the laboratory to make a CAR that attaches to CD19 on the surface of cancer cells and kills them^[4]. The clinical diary of anti-CD19 CAR-T therapy in aggressive lymphomas was written by these products: the commercial availability of the first two (axicabtagene ciloleucel and tisagenlecleucel) facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas and shed light on the feasibility of these products in patients who would not have been eligible for a trial^[5].

The backbone of this approach comes from transplant medicine. The therapeutic advantage of T-cell immunotherapy arises from the graft-versus-leukaemia (GVL) effect observed after haematopoietic stem cell transplantation (HSCT), and donor lymphocyte infusions were already being used to amplify that effect. Adoptive T-cell techniques such as CAR-T cells attempt to harness the GVL effect while minimising the risk of graft-versus-host disease (GVHD), and donor lymphocyte infusions carry a risk of GVHD and have not been as effective in acute leukaemia^[6]. That is the trade the field is trying to make: keep the immune attack on the cancer, drop the immune attack on the patient.

What happens during treatment, step by step?

The preparation is the same in outline for both products. Your white blood cells are extracted from your blood, genetically modified in the laboratory, and then given back to you as a single infusion (drip) into a vein^[3][4]. Two rules follow from how the medicine is made: it must only be given to the patient whose cells were used to make it, and it can only be obtained with a prescription and given by trained doctors in specialist hospitals^[3]. The apheresis step itself is not unique to CAR-T: transfusion medicine, which covers apheresis technology and the development of stem cell transplantation, has found a niche in the development and production of ATMPs for immunotherapy and regenerative medicine purposes^[2].

• Before the infusion – a short course of chemotherapy to clear away your existing white blood cells (described as lymphodepletion in the assessment reports)^[3][4].
• Immediately before the infusion – paracetamol and an antihistamine medicine to reduce the risk of reactions to the infusion; for Breyanzi, other medicines are given for the same purpose^[3][4].
• During the infusion – tocilizumab (or a suitable alternative if it is unavailable due to a shortage) and emergency equipment must be available in case of cytokine release syndrome^[3][4].
• After the infusion – for Tecartus, close monitoring for side effects for 10 days and advice to stay close to a specialist hospital for at least 4 weeks; for Breyanzi, monitoring for one week and advice to stay close to a specialist hospital for at least 2 weeks^[3][4].

Read that list twice before you consent, because it defines the weeks in which you cannot travel far from the treating centre. The reason the monitoring window is written into the label is the safety profile measured in the studies^[3].

What side effects were seen in the studies, and what must you report?

In the clinical study of Tecartus, serious side effects occurred in more than half of all patients. The most common serious side effects, which may affect more than 1 in 10 people, are cytokine release syndrome, encephalopathy and infections^[3]. These are the symptoms to know by name before you go home, because they are the reason for the monitoring period described above.

• Cytokine release syndrome – a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure^[3].
• Encephalopathy – a brain disorder with headache, sleepiness and mental confusion^[3].
• Infections – listed among the most common serious side effects in the same study^[3].

Across anti-CD19 CAR-T therapy more broadly, the adverse effects that need strategies to mitigate them are cytokine release syndrome, neurotoxicity and cytopenia^[5]. If you are taking part in a trial or receiving an authorised product, the practical task is the same: report new fever, vomiting, breathing difficulty, pain, low blood pressure, headache, sleepiness or confusion to your treating team without waiting for the next scheduled visit, because these reports feed directly into the safety monitoring that accompanies the treatment^[3]. Symptoms that reach the treating team are also the raw material of pharmacovigilance, which is how the label can be adjusted later if a pattern appears in treated patients.

What benefits were shown in the trials behind these products?

For mantle cell lymphoma, a main study that is currently ongoing involved 74 adults whose cancer had come back after at least two previous treatments including a BTK inhibitor; around 59% of patients (44 out of 74) treated with Tecartus had a complete response, meaning no signs of the cancer left. For acute lymphoblastic leukaemia, in a main study involving 55 patients, after about 17 months of treatment around 71% (39 out of 55) had a complete response and 56% of all patients (31 out of 55) had a complete response with blood counts returning to normal^[3]. Note the denominators: these are small studies in rare diseases, so the percentages describe a defined group, not a general population.

For Breyanzi, benefits were shown in two main studies involving more than 300 adult patients with DLBCL that had not responded to previous treatment or had returned after at least two courses of therapy or after a stem cell transplant; 53% and 33% of treated patients had a complete response and 73% and 61% had at least a partial response, a decrease in the extent of the cancer in the body. Comparable responses were seen in an analysis of a smaller number of patients with PMBCL and FL3B in these studies, and these results were at least as good as results seen in other studies of patients receiving standard cancer treatments. Another main study involved 184 patients with large B-cell lymphomas that had returned shortly after, or did not respond to, first-line immunochemotherapy, comparing Breyanzi with standard treatment on the time until certain outcomes occurred – treatment not working after 9 weeks, starting a different treatment because the treating doctor considered the current medicine ineffective, cancer worsening or death^[4].

These figures explain why access is restricted to defined groups. Patients with MCL and ALL have poor outcomes, particularly if the cancers come back or did not respond to previous treatments such as a BTK inhibitor in patients with MCL, and the product provides a treatment option for these patients, although serious side effects occur in most patients^[3]. The same logic of measured benefit and measured harm is what you are being asked to weigh when you sign a consent form for a trial rather than a labelled product.

What kinds of cell therapy trials exist beyond authorised CAR-T products?

Anti-CD19 CAR-T therapy with axicabtagene ciloleucel and tisagenlecleucel is approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, was expected in 2020. The commercial availability of the first two products facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas and shed light on the feasibility of these products in patients who would not have been eligible for a trial^[5]. Real-world use is not a substitute for a trial, but it does answer a different question: how the product behaves in the patients that trials tend to screen out.

Promising clinical data have also become available for anti-CD19 CAR-T therapy in patients with indolent B-cell lymphomas or chronic lymphocytic leukaemia, breaking the paradigm that these conditions are not curable, and multiple clinical CAR-T-cell therapy-based trials are ongoing. These include studies comparing CAR-T-cell therapy to autologous stem cell transplantation, studies investigating their use at earlier stages of disease, novel combinations and novel constructs^[5]. If you are offered a trial, one of the first questions worth asking is where in the treatment sequence the study places the cell therapy – after several prior lines, or earlier, in comparison with transplant.

In T-cell non-Hodgkin lymphoma the picture is different. T-cell non-Hodgkin lymphoma is a rare and heterogeneous group of neoplasms of the lymphoid system, typically aggressive, treatment resistant and associated with poor prognosis, with relatively few options of proven clinical benefit for patients with relapsed or refractory disease. Several monoclonal antibodies have been investigated in different subtypes, and CAR-T cells directed against CD30 and immune checkpoint inhibitors are currently being investigated in clinical trials. A treatment being studied in a trial is not the same as an authorised treatment, and trial results for these approaches are still being generated^[7].

Cell-based immunotherapies have shown encouraging results in clinical trials in the treatment of multiple cancers and autoimmune diseases, but parameters such as safety, a high level of specificity and long-lasting efficacy still need to be optimised. As a result, only a few have gained FDA approval, while the majority are studied in the context of investigator-initiated trials (IITs), where academically oriented transfusion centres can play an important role. Transfusion medicine, which covers apheresis technology and the development of stem cell transplantation, has found a niche in the development and production of ATMPs for immunotherapy and regenerative medicine purposes^[2].

Where does stem cell transplant fit, and what is changing there?

Haematopoietic stem cell transplant is a well-established treatment for a number of conditions. Recent and emerging advances in the therapy include the use of haploidentical related donors, conditioning regimens that do not use chemotherapy or radiation, and the early detection and treatment of infections^[8]. For a patient weighing up a transplant trial, these three areas are the ones where the study protocol is most likely to differ from standard care. Survival rates exceed 90% for many haematological malignancies, but patients incur many systemic toxicities and late effects from conventional therapies such as chemotherapy and radiation, and outcomes for patients who do not obtain remission or who relapse are generally dismal – which is the gap that cell-based approaches are trying to fill^[6].

Gene editing has become a clinical reality and is being used in multiple clinical trials and multiple open investigational new drugs, both ex vivo and in vivo, with potential use in regenerative medicine. Several advances in cell-based regenerative medicine have taken place in haematology and immunology over the past two decades, including harnessing gene-editing technology to treat human immunodeficiency virus (HIV), using modified cells and gene therapy to improve clinical outcomes for patients who undergo haematopoietic stem cell transplantation, and the use of engineered T cells for the effective treatment of cancer^[8].

One expectation to set before enrolling: it takes a long time to move cell-based therapies from discovery into the clinic, and efficient development can be facilitated through collaboration between researchers, network building, and education of patients and providers. Patients are increasingly viewed as active participants of humanity-based research rather than as study subjects, and an active and involved patient base is critical to research funding and support. Early engagement with patients is described as necessary to avoid pushback when and if negative effects of new therapies emerge^[8]. In practice, being an active participant starts with reading the protocol summary before you sign and asking what will happen to your data and your cells after the study ends.

How do you find a cell therapy trial, and what does taking part involve?

Adoptive T-cell immunotherapy is offered to patients whose disease has failed to respond to conventional treatment modalities including HSCT, or who are unsuitable for HSCT, while potentially reducing systemic toxicities and late effects. Investigational approaches in this field include antigen-specific T cells and CARs that recognise targets other than CD19, which have helped diversify the field to treat a broad spectrum of haematological malignancies. Survival rates exceed 90% for many haematological malignancies, but patients incur many systemic toxicities and late effects from conventional therapies such as chemotherapy and radiation, and outcomes for patients who do not obtain remission or who relapse are generally dismal^[6]. That mismatch – very good average survival set against very poor survival after relapse – is the reason investigational options are a real conversation rather than a last resort.

When you look for a study, use public registries rather than advertisements. The EU clinical trials information system and the EU portal for clinical trials list authorised studies in the European Union, ClinicalTrials.gov lists studies worldwide, and the WHO ICTRP aggregates multiple national registers. Trials recruiting in Europe can also be searched on clinicaltrials.eu. Registries are the appropriate starting point because they publish the information you need to check before contacting anyone: the condition being studied, the phase, the inclusion and exclusion criteria, and the recruiting site – and because academic capacity for this work often sits inside transfusion centres and cell-therapy units rather than in commercial settings^[2].

Before you agree to take part, ask the study team to walk you through the schedule: when your cells will be collected, how long the laboratory step takes, how many visits the protocol requires, how long you must stay near the hospital, and which medicines you must stop or continue. The Tecartus and Breyanzi assessment reports show how much of the patient pathway sits inside the monitoring window – close monitoring for 10 days and advice to stay close to a specialist hospital for at least 4 weeks after Tecartus, and monitoring for one week with at least 2 weeks near a specialist hospital after Breyanzi^[3][4]. If you cannot meet that requirement, say so before enrolment.

How do you recognise an unregulated cell therapy?

Unregulated advanced therapies may put patients at risk of serious side effects without any proven benefits, and they are often sold on websites or through social media channels as a last hope, exploiting the worries of patients and their families. Authorities are clamping down on those supplying unregulated ATMPs and encourage patients and caregivers to report suspicious cases to their national authorities. The EMA's Committee for Advanced Therapies and the Heads of Medicines Agencies released a statement on the risks of unregulated advanced therapies following reports of providers offering unregulated dendritic cell therapies for cancer treatments in the EU, with practical advice for patients and caregivers on identifying them; the joint statement was published in March 2025^[1].

Warning signs that an advanced therapy may be unregulated and illegally supplied are specific and checkable^[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; and if you have questions or concerns, reach out to your country's competent authority or to the EMA^[1].

When should you contact your doctor or pharmacist?

Contact your treating team without waiting for the next appointment if, after a CAR-T infusion, you develop fever, vomiting, shortness of breath, pain or low blood pressure, or headache, sleepiness and mental confusion – these are the symptoms of the serious side effects that the monitoring period exists to catch. Report infections too, as they are among the most common serious side effects. If you are in a trial, your study team is the first point of contact for any new symptom, and your treating doctor or pharmacist can explain how the product you received is meant to be used and what to watch for^[3]. If you are unsure whether a symptom is related to the treatment, say it out loud anyway – the treating team has the schedule and the records, and you have the symptom.

Summary

Cell therapies for leukaemia and lymphoma are a small, tightly defined group of medicines. The CAR-T products described here are authorised only for named diagnoses and only after a specified number of prior treatments, they are made from your own cells, and they are given in specialist hospitals with tocilizumab and emergency equipment on hand. Their mechanism is shared – a modified T cell that recognises CD19 on the cancer cell – but their labels, their monitoring windows and the studies behind them differ, and those differences are written into the public assessment reports you can read before consenting^[3][4].

What most affects your daily life as a participant is not the mechanism but the calendar: a course of chemotherapy before the infusion, a single infusion, then 10 days of close monitoring and at least 4 weeks near a specialist hospital for Tecartus, or one week of monitoring and at least 2 weeks for Breyanzi. Plan for that window before you consent, ask where in the treatment sequence the study places the cell therapy, and treat any therapy offered outside an authorised trial or a registered study as a reason to verify approval with a competent authority before going further. Finding a study means starting from a registry entry rather than an advertisement, and being a participant means treating your own symptom reporting as part of the evidence the field depends on^[2].

1. [1] Advanced therapy medicinal products: Overview (accessed 02 June 2026) — https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-products-overview
2. [2] Overview of Cellular Immunotherapies within Transfusion Medicine for the Treatment of Malignant Diseases - PMC — PubMed Central (accessed 06.10.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC8151282/
3. [3] Tecartus | European Medicines Agency (EMA) (accessed 02 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/tecartus
4. [4] Breyanzi | European Medicines Agency (EMA) (accessed 02 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/breyanzi
5. [5] CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences - PMC — PubMed Central (accessed 06.10.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC7326110/
6. [6] Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances - PMC — PubMed Central (accessed 06.10.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC4649603/
7. [7] Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas - PMC — PubMed Central (accessed 06.10.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC6162531/
8. [8] National Academies of Sciences, Engineering, and Medicine. Hematologic and Immunologic Applications. In: Exploring the State of the Science in the Field of Regenerative Medicine: Challenges of and Opportunities for Cellular Therapies: Proceedings of a Workshop. Washington (DC): National Academies Press (US); 2017. (accessed 02 June 2026) — https://www.ncbi.nlm.nih.gov/sites/books/NBK436806/