Mohamad Mohty, MD, PhD, Discusses Cytotoxic T Lymphocytes as Potential EBVPTLD Therapy

Transplantations can sometimes result in malignancies like Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBVPTLD), which can be a life-threatening condition due to immunosuppression. However, therapies like cytotoxic T lymphocytes (CTLs) are emerging, providing potential treatments for the serious condition.

While at the 60th ASH Annual Meeting & Exposition in San Diego, California, Mohamad Mohty, MD, PhD, head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital in Paris, France, sat down with Rare Disease Report^®(RDR^®) to discuss the investigational therapy and relay the potential clinical implications.

[Editor’s note: Transcript is slightly modified for readability.]

RDR^®: Can you provide some background on EBVPTLD and therapies for the rare disorder?

Mohty: “In this ASH 2018 annual meeting held in San Diego, we've seen a lot of research and data about CAR T-cells in different malignancies, acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma, myeloma, chronic lymphocytic leukemia (CLL), but also emerging data in AML.

It's not only about the CAR T-cells, but some of these CAR T-cells are being combined with novel drugs in order to increase the efficacy and/or safety. Beside the excitement about CAR T-cells, as a transplanter, I myself am also very interested in other cellular therapies that can be useful in the allogenic stem cell transplant setting.

Actually, I noticed, with great interest, the data presented about the use of EBV of CTLs directed against EBVPTLD with central nervous system (CNS) localization. In this meeting, there was a presentation involving 19 patients with an overall response rate of more than 60%, including complete remission and excellent survival at 1 year—with a very good safety profile.

I believe this is very important information because EBVPTLD—after transplantation, whether it’s a stem cell transplantation or a solid organ transplantation—is a really serious life-threatening condition. Currently, the only available tools are the anti-CD20 monoclonal antibodies.

When patients fail, we use conventional chemotherapy, but this is not optimal, and this is why the development of these CTLs directed against EBV is really very important and eagerly awaited. This is also why I'm very pleased to see that there are 2 actually ongoing phase 3 trials looking into the efficacy and safety of these CTLs directed against the EBV.”

RDR^®: What were the main hallmarks you observed in the data?

Mohty: “The major teaching for me from the different results presented at this ASH meeting regarding cellular therapies or the novel targeted therapies is that it is likely we will be able to get rid of some of the conventional or traditional chemotherapy in the near future and move quickly into a chemo-free zone.

Given the side-effects of a different chemotherapy agent, I think this is really good news for the field but also for the patients.

I think when you are treating very bad hematologic malignancies, the ultimate goal is to cure patients or extend their overall survival. However, you also need to achieve this with the lowest incidence of side-effects and preserve the quality of life of the patient. This is why the development of agents and tools that can allow the avoidance the traditional toxic chemotherapy agent is very welcome in our field.”

RDR^®: What are some of the traditional challenges this treatment helps address?

Mohty: “For this patient population, when it comes to treating EBVPTLD after stem cell transplantation or solid organ transplantation, patients are usually a very sick, heavily pretreated, and have comorbidities. In that case, ideally, you would like to avoid adding toxicities as is the case with traditional chemotherapy.

This is why whether it's an EBV or other viral related complications, it's very important to be able to develop these cellular therapies.

The next steps when it comes to the development of cellular therapies are definitely to move these tools earlier into the treatment algorithm. At the moment, most of the cellular therapies—whether the CAR T-cells or other cellular therapies like the CTL directed against EBV—are used in a salvage refractory setting. I think we would like to move these cellular therapies earlier in the management of patients because this is likely where we will be more effective and less toxic, in my opinion."