Around 5000 people in the Netherlands are diagnosed with lymphoma each year. This thesis of Johanna Bult focused on two types of B-cell-derived lymphomas: marginal zone lymphoma and diffuse large B-cell lymphoma.

We explored the clinical and biological factors underlying the development and transformation of lymphoma, as well as ways to improve its treatment.

We found that marginal zone lymphomas occurring in the salivary glands of patients with Sjögren’s syndrome are characterized by a small number of mutations. In addition, several factors associated with the development of transformed marginal zone lymphoma were identified: age above 60 years, prior systemic therapy before transformation, and the acquisition of germinal center B-cell features. These findings contribute to a better understanding of lymphoma transformation and may help to detect it earlier and treat it more effectively.

We also investigated the value of circulating tumor DNA (ctDNA) as a biomarker to evaluate treatment response in patients with diffuse large B-cell lymphoma. ctDNA showed to be a promising tool. However, further research is needed to improve its sensitivity, and its use should be standardized before it can be implemented in clinical practice.

Finally, we observed that adding the PD-L1 inhibitor atezolizumab to R-CHOP treatment improved survival outcomes in patients with diffuse large B-cell lymphoma.