CAR-T Meeting 2024 | The risk of secondary malignancies following CAR T-cell therapy: current evidence

Secondary malignancies are also one of the different hot topics that we have nowadays with this type of treatment strategy, and I think that we have to be quite careful when we think about secondary malignancies in patients being treated with CAR-T.

I would say that any chemotherapy or radiotherapy treatment is associated with an increased risk for secondary malignancies in the patient that receives this chemotherapy and radiotherapy. CAR-Ts are not being used as a first-line treatment strategy in most of the patients, so when we think about secondary malignancies it’s always a little bit complicated and difficult to demonstrate that these secondary malignancies are exclusively being associated to the administration of CAR-T or might be related not only to CAR-T, but to the amount of chemotherapy and eventually radiotherapy that the patient has received before (even high-dose chemotherapy and stem cell transplantation in some of the patients that receive CAR-T).

After having said that, it’s true that we are receiving or that we are having more and more information on the secondary malignancy profile in patients receiving CAR-T. This is a reality that there is a small proportion of patients that develop secondary malignancies, and this is why long-term follow-up of these patients is extremely important. And all the surveillance strategies that are already in place are very important to better understand what are going to be the long-term outcomes of these patients and of course the long-term side effects, because we know quite well which are the short-term side effects of CAR-T. 

Talking about secondary malignancies, maybe the information that we received back in December 2023 from the FDA that there were some patients that developed T-cell lymphoma after being treated with a CAR-T construct was of special interest. Of course it created a lot of alarms and concerns to, let’s say, maybe not exactly to the scientific community, but of course to the patients and patients’ families and patient advocacy groups.

This is one aspect that’s in the process of being analyzed in large registries with a bigger number of patients. I want to mention one of the presentations, by Marco Ruella from UPenn in this EU CAR T-cell meeting in which he was mentioning, especially, a retrospective analysis that they did with all the patients being treated in UPenn and the reality is that the number of cases was almost zero. There was one patient but with a lot of question marks in this regard.

And of course, when you [weigh up], the pros of using CAR-T and the capacity of CAR-T to cure these patients that were incurable (or many of them were incurable in the past before CAR-T) and the possibility of developing, in a very small percentage, secondary malignancies or T-cell lymphomas, of course, the balance goes in favor of the efficacy of CAR-T.