The PhD work by Niels van Nieuwenhuijsen (UMC Utrecht) has further unraveled the disease biology of multiple myeloma (MM), one of the most prevalent plasma cell disorders. Amongst others, they used diagnostic biomarkers and laboratory testing of candidate drugs on MM cells of patients. This research revealed that the future, therapy choices are determined by measuring the presence or activity of predictive biomarkers and may result in more personalized therapeutic approaches.
Multiple myeloma (MM) is one of the most prevalent disorders of plasma cells, the main effectors of humoral immunity by producing and secreting immunoglobulins that target foreign antigens. For decades, treatment choices have been few, and those available were tailored merely to a patient’s age and comorbidities. Currently, treatment choices are usually adapted to clinical parameters (such as age, comorbidities) and cytogenetic features. However, with increasing knowledge about pathogenesis, genomic evolution and response to therapy, new and more intelligent treatment paradigms for relapsing or refractory MM are surfacing. The work presented in the PhD thesis of Niels van Nieuwenhuijzen, MD (Center for Translational Immunology and Department of Hematology, UMC Utrecht) contributes to a future in which therapeutic strategies in MM will become ever more adapted to the individual patient.
Treatment selection
Different chapters of his thesis have focused on either unravelling disease biology to reveal novel genetic and molecular biomarkers of therapy response or ex vivo treatment of patient-derived MM cells to measure drug sensitivity. Ultimately, some combination of both strategies might prove best in informing clinicians on choice of therapy in patients with relapsed MM.
In more detail, as a patient progresses through multiple lines of relapse and collects new mutations, ex vivo drug sensitivity measurements can be used to select the best treatment from the basket of drugs that have not been used yet. Alternatively, van Nieuwenhuijsen proposes that ex vivo models can also be used to test whether the myeloma clone is still, or again, sensitive for a drug that has been previously used. For each approach to prediction of response to therapy, one will need to measure to determine the best way forward.
“I envisage a future in which choices of first or second lines of therapy are determined by measuring the presence or activity of a certain biological predictive biomarker. As such, we will use more rational therapy regimens based on a patient’s biological disease characteristics.”
Multiple myeloma
Multiple myeloma (MM) is a malignant growth of clonal plasma cells, primarily located in the bone marrow and is one of the most common hematological cancers. MM cannot be cured, but survival has improved with the introduction of immunomodulatory drugs and proteasome inhibitors. Nevertheless, the 5-year survival rate does not exceed 60 percent. Data collected by the Dutch Federation of Cancer Patient Organizations (NFK) and the Netherlands Comprehensive Cancer Organization (IKNL) over 2024 shows that more than 1.500 people were diagnosed that year with MM in the Netherlands, mostly in people of 60 years and older and affecting men more than women (59 versus 41 percent).
PhD defense
Niels van Nieuwenhuijzen, MD (1993, Bergen op Zoom) defended his PhD thesis on February 19, 2025 at Utrecht University. The title of his thesis was “To measure is to predict – Characterization of response to therapy in plasma cell disorders”. Supervisor was prof. Monique Minnema, MD PhD (Center for Translational Immunology and Department of Hematology, UMC Utrecht). Co-supervisors were Victor Peperzak, PhD and Marta Cuenca Lopera, PhD (both Center for Translational Immunology, UMC Utrecht). In 2023, Niels van Nieuwenhuijzen started working as a resident at the Diakonessenhuis and UMC Utrecht to become an internist-hematologist.
