Immunotherapy with so-called CAR-T cells has established itself for the treatment of various leukemias (blood cancer) and lymphomas (lymph gland cancer). A team led by Dr. Kai Rejeski and Prof. Marion Subklewe from the Medical Clinic III of the LMU Klinikum found that many patients suffer from a side effect that initially fell under the radar: a sometimes life-threatening, sometimes long-lasting drop in blood cells. Together with international partners, the Munich team has examined the phenomenon in more detail and developed a score with which high-risk vs. low-risk patients can be stratified for this CAR-T-cell side effect before starting therapy.
It is an old dream of medicine: to focus the immune system of cancer patients on the tumor cells in the body and to fight the life-threatening disease effectively. Recently, at least in the treatment of refractory lymphomas and leukemia, it has come true: adoptive immunotherapy with CAR-T cells is an innovative and effective therapy strategy that changes the previous therapy landscape. CAR-T stands for “Chimeric Antigen Receptor” T cells, whereby the body’s own T cells are directed against the tumor. In the course of the therapy, T cells are first removed from the patient, which are genetically engineered so that they recognize a target structure (CD19) on the surface of the tumor cells. The patients initially receive three days of chemotherapy, so that the CAR T cells can optimally develop their effect in the body. By precisely binding the CAR T cells to this target structure, the tumor cells can be destroyed.
As with almost any medical therapy, this cannot be done without side effects. Initially, the experts only focused on the “cytokine storm” (also known as a symptom of severe courses of COVID-19) and the negative effects on the central nervous system. “But then we noticed that many of those treated suffer from a drop in blood values, a so-called cytopenia. The frequency was particularly surprising, ”explains Marion Subklewe.
Specifically, her team, together with French and US clinics, defined three typical courses among the patients. Dr. Rejeski describes it as follows: “About a quarter of the patients have no blood count problems whatsoever during therapy; they regenerate normally. However, the vast majority (> 75 percent) develop cytopenia; It is typical here that the blood values initially recover before they then fall again – a so-called biphasic course. In addition, around 20 to 25 percent of patients have very bad blood values - for up to two months or, in rare cases, longer. ”During this time, they are prone to infections, in the worst case it can also lead to life-threatening sepsis (“ blood poisoning “) come. “We have to keep this in mind when managing the therapy, because these patients need, among other things, antibiotics to prevent infections, ”emphasizes Subklewe. In addition, the blood values must be checked closely.
In order to predict the development of cytopenia in CAR-T cell therapy, the Munich team has developed a model, the so-called CAR-HEMATOTOX Score. This consists of the normal blood count values and two inflammation parameters. The analysis showed that these parameters were particularly associated with long-lasting cytopenias, which probably play a role in the pathomechanism of the side effect. The researchers worked with first author Dr. Kai Rejeski examined in a study with the international cooperation partners. Result: If a patient has a low score, the probability, according to Subklewe, is “very, very small that she will develop cytopenia.” For the remaining patients, “we are not quite as good in our prediction” says the doctor,
This is important, because in the future the CAR-T therapy should also be given outside of studies on an outpatient basis – i.e. not in the clinic. Under these circumstances, it is particularly important to know early on who is at risk for a prolonged cytopenia phase – and who is not.
The paper is published in Blood