KOL Perspective: CAR T-cell Therapy

Interview Transcript

Article | KOL Perspective: CAR T-cell Therapy
11th February 2021 Atheneum Team

Expert Profile


Director of the Department for Haematology, Oncology, and Pneumology


University of Münster


Georg currently serves as the Director of the Medical Department A for Haematology, Oncology, and Pneumology at the Münster University Hospital in Germany and is a specialist in Haematology and Oncology. The Medical Department A is one of the main centres in Germany in the field of malignant lymphomas, acute leukaemia, sarcomas, stem cell and bone marrow transplantation. He is the referring physician for CAR-T within the centre and is a member of the core CAR-T team, where he is involved in most of the processes in the delivery of CAR T-cells to patients.

Section 1: Current CAR T-cell Therapy

1.1. How would you describe the current CAR T patient journey?

In Europe and also in the US, CAR T-cells are approved for the treatment of patients with different subtypes of aggressive lymphoma, specifically with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed follicular lymphoma after two lines of therapy; so in the third line. These patients normally have received different therapies beforehand, and they have either not responded to these therapies or they have relapsed after an initial response. So normally at least in our center we get many patients transferred from smaller hospitals or private practices. We evaluate the patients regarding comorbidities and about their status. If they’re fit enough to receive CAR T-cells, we frequently decide to treat these patients with this novel approach.

Before or after we harvest the T-cells we frequently perform a bridging therapy. Our main goal is to get the patient into remission while the CAR T-cells are manufactured. If a patient responds, then we will apply the CAR T-cells. As I mentioned, patients have to have received at least two prior lines of therapy before you can use CAR T-cells that they’re reimbursed.

In general, the treatment with CAR T-cells is rather complicated. First you have to perform the apheresis, subsequently you frequently need to treat the patients with a bridging therapy while the CAR T-cells are manufactured. Subsequently patients receive the CAR T-cells. CAR T-cells therapies are delivered in Germany in the hospital and patients need to stay at least for 10 days in the hospital to monitor for side-effects.

1.2. How are patients referred for CAR T therapy?

Patients are frequently referred from smaller hospitals. We subsequently evaluate the patients if they can tolerate a CAR T-cell therapy.

With regards to outpatient vs. inpatient, I think this is really a question of where you practice. An outpatient treatment is especially an issue for US based doctors as they have a completely different setting on outpatient services. The patient is not in the hospital, but he’s in the hotel next to the hospital, so to speak, and there are nurses around and that’s very well organized. At least in Germany, this is not the case so at this stage doing CAR T-cell therapies in an outpatient setting is not an issue in Germany. Potentially it might develop over time when we get more experience, but at this stage, this is really not a big issue. Secondly, the predominant costs of the CAR T-cell therapies are not so much the costs to stay in the hospital, but rather the product, which by itself is very expensive.

1.3. What are the main bottlenecks in the CAR T patient journey?

Manufacturing has really substantially improved overall. I think the bottlenecks are first that we get to see the patient early enough that we don’t see the patient in later lines, that we really see the patient in third line, because as I’ve said before, then efficacy is better. Secondly, it is important to get the patient into a remission before we apply the CAR T-cells as, from most of the data that we have patients that have a progressive lymphoma normally do not respond to CAR T-cells.

There are two approved products, one from Novartis and one from Gilead Kite, and with both companies, the manufacturing has substantially improved.

1.4. What are your thoughts on the reimbursement of CAR T-cell therapies?

We are still applying to the health insurance company of the patient and are asking them for reimbursement. They receive an application from us. Based on this application they will either approve and reimburse the CAR T-cell treatment or they reject the application. If we are within the indication, how the CAR T-cell products are approved, they are normally reimbursed. So that is not an issue, but we clarify reimbursement before application.

1.5. What are the greatest unmet needs around clinical use of CAR T-cell therapies?

CAR T-cells obviously work better in patients that are in a remission after bridging therapy. Thus, the biggest unmet need is really to improve the efficacy for patients who are having a progressive lymphoma.

Section 2: Future of CAR T-cell Therapy

2.1. How will the patient journey for CAR T change in the future?

Studies comparing autologous stem cell transplantation to CAR T-cell therapies have recently been completed. If CAR T-cells are superior to transplantation, CAR T-cell therapies will move up one line in therapy. Therefore, more patients will receive CAR T-cells. I think all of the organizational steps will improve and manufacturing probably will be performed quicker which will improve the speed of the whole process. Lastly, I think the more patients we treat with CAR T-cells, the more we get used to dealing with side effects and so we will improve there as well.

From the pharmaceutical companies, I think predominantly that they can improve the processes with respect to manufacturing. I think that’s an important step.

2.2. What oncology indications will see future CAR T treatment?

I think in the near future, not only we will have approved products for diffuse large B-cell lymphoma, but we already know that there are very promising data for multiple myeloma and also for other lymphoma subtypes, such as mantle cell lymphoma and chronic lymphocytic leukemia. I also think that we will have other CAR T-cell products which target other antigens, or which target more than just one antigen because at the current situation, the approved products are all targeting CD19.

If you think outside of B-cell lymphomas we will need other specific antigens. There are several trials running in solid cancers thus far. They have not been such a big success story compared to the B-cell lymphomas. However, I think this might change.

2.3. What could be the role of allogenic CAR T therapy in clinical settings?

The big advantage with allogenic CAR T-cells is that you can have them essentially off the shelf. There are trials running for allogenic CAR T-cells. We will see if allogenic CAR T-cells really are as efficacious as the autologous CAR T-cells. I think more work and more research, and more trials are needed to really define the role for allogenic CAR T-cells in the treatment of patients with B-cell lymphoma.

I don’t think allogenic T-cells will be a first line treatment option in the near future. Our first-line treatment is rather efficacious with the combination of rituximab and CHOP chemotherapy. With this approach we cure roughly 60% to 70% of affected patients. I really don’t see at this stage that CAR T-cells will be used as front-line treatment due to the rather complicated process and the costs.

2.4. What would you look for in a CAR T-cell therapy product profile?

For me, the most important factors are efficacy and tolerability. A therapy that is highly efficacious and very well tolerable but has a complicated mode of application is not a problem. Whereas if you have a very easy way of applying a drug, which doesn’t work, that doesn’t help us. It really comes down for me to efficacy and tolerability and it’s obviously we’re looking for something highly efficacious and tolerable.

2.5. What role does Real World Evidence have for CAR T-cell therapies?

The study data for the CAR T-cells are published and available. On the other side, we have real world data and some of them suggest that the efficacy is lower compared to the data from the studies, which makes sense because that is not unusual for real world data. However, real world data is really important as there, we really do not have a selection bias as in clinical trials. We do not exclude the bad patients who are often unfortunately excluded in clinical trials.