Better Prognosis for Blood Cancers

The latest figures from the Swiss Cancer League speak for themselves: every year around 1,200 people in Switzerland are diagnosed with leukemia, which corresponds to 2.7 percent of all cancer cases. It is somewhat more common in men than women (60 versus 40 percent), and it is the most common type of cancer in children. And yet, we still know little about the exact causes of leukemia. It’s clear that in a healthy person, the body forms exactly the amount of blood cells that it needs. In leukemia, however, the precursor cells of the red and white blood cells or platelets do not fully develop but still multiply in the blood and block the healthy blood cells’ functioning.

UZH professor of hematology Thorsten Zenz treats patients with leukemia and lymphomas at the University Hospital Zurich. Lymphoma is characterized by the uncontrolled proliferation of white blood cells, also called lymphocytes. Thanks to modern therapy options, says Zenz, the prognosis for first-time patients is much better today than it used to be. A wide range of treatments is available for children as well as adults – from the standard intensive chemotherapy to new immunotherapies such as stem cell transplantation or CAR (chimeric antigen receptor) T-cell therapy. “Thanks to these therapies, the outcomes for patients have improved significantly. Many leave our clinic cured,” says Zenz.

And yet the story does not end with a happily ever after for all patients. For some, the treatment is ineffective, while for others, the cancer returns. Depending on the type of blood cancer, the relapse rate varies considerably.

Three years ago, Thorsten Zenz launched the INTeRCePT research project to gain a better understanding of why some patients respond well to treatment and others do not. The researchers in the consortium, including Burkhard Becher (UZH), Nico Beerenwinkel (ETHZ), Jean-Pierre Bourquin (KISPI/UZH), Wolfgang Huber (EMBL), Andreas Moor (ETHZ), Berend Snijder (ETHZ) and Stefanie Kreutmair (USZ/UZH), are primarily investigating non-Hodgkin’s lymphomas. These are malignant diseases of the lymphatic tissue. The lymph nodes are most commonly affected, but other organs such as the lungs, liver, bone marrow or spleen can also be affected – especially in advanced stages of the disease.

The researchers want to gain a better understanding of which drugs or therapies work best for which kinds of patients, and thus reduce the likelihood of relapses. “We don’t yet know exactly how the cells of a lymphoma are structured, for example, and therefore which therapy works best to combat them.” INTeRCePT is designed to take into account individual patients’ specific conditions, thus taking a personalized approach as used in precision medicine. The research study includes patients who did not respond to the first treatment or who have had a relapse of the cancer.

The INTeRCePT project is scheduled to run for five years. In the first three years, the focus was on basic research; now in summer of this year, the clinical trial will begin. As part of the basic research, tissue and blood samples were analyzed in the laboratory, and the researchers tested the effect of various medications on the tissue. The analysis went as far as individual cell level. “For the first three years, we generated as much data as possible and included over 200 patients in the study,” says Zenz. Time was an important aspect, he explains: “We tested how quickly the immune cells and the tumor cells reacted to the medication.”

In a follow-up study also starting this summer, Zenz and his research group will work with high-risk patients receiving CAR T-cell therapy and additional treatments. It is planned that 50 patients will take part in this randomized study, 25 of whom will receive the standard therapy and the other 25 will be given a risk assessment tailored to them and then, depending on the result, will receive a therapy based on cell analyses. “The personalized therapy is based on highly complex diagnostics that help us to put together the right mix of medication and treatments and also to learn for the future which cases have a risk of relapse and which do not,” says Zenz. 

By analyzing the data, the researchers will be able to draw a detailed map of drug responses at individual cell level. This will enable them to derive a more widely applicable procedure for the treatment of blood cancers in the future. The aim is to increase the response rate by 50 percent.