Ingrid Glimelius – Clinical, epidemiological and tumour biology studies of different cancer forms

Our research is based on our clinical knowledge, where we identify relevant questions and use the strength from several different methods, the many national and local registries Sweden, possibilities to perform clinical trials, and translational biological studies.

Three pictures, one with graphs and the text epidemiology and statistics, one with a microscope image of cells and the text tumour biology and translational studies, and one with a stethoscope and medicine bottles and the text cancer care and oncology.

Research in the group rests on three pillars: epidemiology and statistics, tumour biology and translational studies, and cancer care and oncology, that are mutually dependent on each other.

We are studying and trying to help patients with:

Malignant lymphomas
Gynecological tumours
Testicular cancer

Lymphoma, ovarian cancer and testicular cancer

Our thorough mapping of patients has attracted considerable interest in our research, both nationally and internationally. We have been able to evaluate the effects and side effects of oncological treatments over the very long term, e.g. chemotherapy in children and radiotherapy in young adults, which has been successful. Our studies of survival among cancer patients (primarily Hodgkin's lymphoma and testicular cancer patients) have yielded results that are applicable to entire patient populations, including patients who are never included in clinical trials.

Our research concerns patients with various subtypes of lymphoma, such as mantle cell lymphoma, Hodgkin’s lymphoma, diffuse large B-cell lymphoma and more rare subtypes. We also collaborate with the lymphoma group in Uppsala, led by Gunilla Enblad, and with the lymphoma group at the Karolinska Institute, led by Karin E Smedby.

In addition to lymphoma, we also study other solid cancers, particularly ovarian cancer and cervical cancer. We also have ongoing studies in testicular cancer that are strongly anchored in the SWENOTECA (Sweden Norway Testicular Cancer) group.

Clinical and tumour biology studies of lymphoma, focusing on mantle cell lymphoma

Mantle cell lymphoma is currently one of the lymphomas with poorest long-term survival and novel treatment concepts are urgently needed. However, in addition to the expected short survival there are also other challenges such as an ageing population, many new drugs and difficulties knowing for which patient groups new drugs should be introduced.

Graph showing that the survival in mantle cell lymphoma is lower for older patients.

The survival is still poor for patients with mantle cell lymphoma and the aging population is a challenge in selecting the right treatment.

Risk of a secondary malignancy

We are currently starting the large SCUBA trial (Early detection of second primary malignancies in cancer survivors in the U-CAN biobank). This is a collaboration with several researchers and clinicians that gather biomaterial in the large U-CAN biobank.

In this trial we aim to specifically study the risk of a new secondary malignancy after that you have been burdened by a first cancer. We strive to describe risk, identify new biomarkers and ultimately limit this fatal side-effect. We would like to increase knowledge on what patients are burdened by this risk and if we can avoid certain treatment in specific patients to limit the risks.

All patients inclued in clinical trials also leave blood and tissues samples for the U-CAN biobank, which allows for translational studies and discoveries of new biomarkers.

International studies and clinical trials

By active participation in the Nordic Mantle Cell lymphoma group, we have been involved in introducing and evaluating several new targeted drugs for mantle cell lymphoma. Studies on mantle cell lymphoma patients include both academic clinical trials, e.g. the Nordic ALTAMIRA study, the Nordic-British ENRICH study, the Nordic Valeria study and the European PLATO study, and biological research on tumour microenvironment and registry studies.

Researchers from Uppsala also participated in the European TRIANGLE study that recently showed that adding the tyrosine kinase inhibitor Ibrutinib to chemotherapy could markedly improve survival. This addition of targeted therapy in mantle cell lymphoma has already resulted in increased survival.

New treatments

Lately, many new therapies have been introduced for mantle cell lymphoma, such as bi-specific antibodies, chimeric antigen receptor T (CAR-T) cell therapy and antibody–cytostatic drug conjugates. At the clinical trial unit at Uppsala University Hospital, we perform trials that aim to identify the best combinations of these new treatments with our traditional therapies.

Today we offer mantle cell lymphoma patients access to bi-specific antibodies (glofitamab), advanced CAR-T cell therapies (Tercartus), and modern CAR-T cells in the CARMA study. These immunological therapies provide a chance for long-term survival for patients with this difficult to manage disease.

Tumour biology in mantle cell lymphoma

To date, there have only been limited studies of the tumour microenvironment in mantle cell lymphoma and in this area we are currently collaborating with clinical genetics in Uppsala, as well as with researchers in Lund and Denmark. We are also focusing on mapping many aspects of tumour biology in mantle cell lymphoma, using genetic and epigenetic methods as well as classic pathology methods.

Through the U-CAN database, we are also collecting tumour material that we have begun to analyse in order to find markers for the very early detection of lymphoma recurrence by measuring measurable residual disease (MRD). Here, we are currently testing superRCA – a way of measuring incredibly small remaining amounts of lymphoma in blood samples – which we use to guide the treatment of our patients.

Late effects of cancer

Future childbearing

Our studies of childbearing in patients who have previously had Hodgkin's lymphoma have attracted considerable international interest. In collaboration with Caroline Dietrich and the Department of Clinical Epidemiology in Stockholm, we have shown that women who have previously had Hodgkin's lymphoma do not face an increased risk of relapse if they wish to become pregnant after completing treatment. We have also shown that with modern intensive cytostatic drugs, the majority of female cancer survivors are able to become pregnant and have children.

We are conducting very active research into various aspects of childbirth and the risk of several different types of cancer. We are collaborating with researchers from the Nordic countries and the United States within the Nordic group for perinatal risk factors and cancer. Research into pregnancy and cancer is an important field, as it is now common for women to delay childbirth, which sometimes coincides with the onset of cancer and can also affect the risk of cancer.

Follow-up of young adults

A new area of research we are working on is follow-up after cancer in both children and young adults. Being diagnosed with cancer as a young adult can lead to both psychological and physical complications later in life. Together with Hanna Mogensen, we have started a pilot study for follow-up of 18–30-year-olds. The aim is to help patients with everything from returning to work or studies after cancer treatment, rehabilitation, relationships and physical late effects. We then follow up the interventions with both questionnaires and register studies.