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Friso Calkoen: ‘We’re getting to grips with the intricacies of CAR-T’

The introduction of CAR-T therapy in pediatric oncology meant a spectacular improvement in the chances of children with leukemia. Meanwhile fifteen children of the Princess Máxima Center have undergone the treatment. Fellow Friso Calkoen talks about the developments. ‘It’s not a panacea, but this treatment really adds something to the existing forms of therapy in pediatric oncology.’

With CAR-T, our own immune system helps destroy leukemia cells. Friso works as a pediatric oncology fellow on this innovative immunotherapy. ‘I started here two years ago after I graduated in pediatrics. I have been intensively involved in the CAR-T program for the past year. Developments are moving at lightning speed. This treatment really adds something to the existing forms of therapy: radiation, chemo and surgery.’ Currently CAR-T is available for children with B-cell acute lymphatic leukemia (ALL) for whom other treatments no longer work. 

Better understanding

Although the Máxima has been working on it only very briefly, a great deal has already been learned. Friso says, ‘In the beginning, the main focus was on how to do this safely. These are extremely vulnerable children and adolescents, often with years of treatment behind them. But from the start we have also been thinking about what determinations we need to make during the blood tests. And we’ve been working on the storage and analysis of blood samples to gain a better understanding of what happens to the children who are given CAR-T cells. In this way we try to find out which children react well or not so well, and why that is. That kind of clinical information is indispensable in order to be able to keep improving the treatment.’ It is essential that all expertise is combined here at the Máxima, so we do not need to refer: chemotherapy, immunotherapy and diagnostics, enabling us to decide what is best for the patient.


Tricks of the trade

In the meantime we are getting better and better at the Máxima, according to Friso. ‘There is growing confidence that we can prevent or manage side effects and complications – inflammation in particular is a major risk – should they occur. A serious complication is a so-called cytokine storm, an overreaction of the immune system. If you do not suppress it, a combination of high fever and low blood pressure will occur, potentially resulting in fatal organ damage.’ Another ‘trick’ concerns the moment of administering the CAR-T cells. This is best done when the leukemia is still actually present. That is rather counterintuitive, according to Friso. ‘Everybody’s been trying to eliminate the leukemia completely all the time. And now you’re going to sit and wait while you have the inclination to take immediate action. But that ‘waiting’ is crucial in order for the CAR-T to take optimal effect.’


No panacea

CAR-T is promising, but it is not a panacea, Friso emphasizes. ‘In the literature we see success rates of between 40 and 60 percent. We’re not doing any better than that yet. But the possibilities are very interesting, in time also for other types of cancer. We know from the U.S. that the first patients are doing extremely well eight years after their successful CAR-T therapy. This therapy really contributes to the mission of the Máxima: not only cure, but also good quality of life.’


More information

CAR stands for chimeric antigen receptor, while T stands for T cells in the immune system. CAR-T cells are made from the child’s own cells. These are modified and returned via infusion. The modified own immune cells then detect cancer cells and kill them. The results are often spectacular, but unfortunately every time it is a question of wait and see whether the treatment is successful. For more information see an earlier interview with Peter Hoogerbrugge in the parent newsletter. In that article you will find links to information and a video about the therapy. During the introduction at the Máxima in 2019, a news item was also posted on the site.