Researchers discover new tools in regular blood samples for developing precision therapies for lymphoma

Tumour DNA circulating in the bloodstream of patients with aggressive lymphoma has a previously unknown and even crucial role in the identification of effective therapies for this serious disease.

In a recently completed study, researchers from the University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center investigated the characteristics and clinical significance of circulating tumour DNA (ctDNA) found in the blood of patients with aggressive lymphoma. The study was carried out through Nordic collaboration.

Analysed in the study were blood samples of lymphoma patients treated in a Nordic Lymphoma Group trial, which were collected before, at the mid-point of and after treatment.

Increasingly accurate diagnostics and more effective therapies

“The analysis of ctDNA in the blood samples revealed significant diagnostic features, not all of which were found in regular tumour biopsies,” says Professor Sirpa Leppä from the University of Helsinki and the HUS Comprehensive Cancer Center.

The researchers found that the concentration of ctDNA in blood before therapy varied considerably between patients and was comparable to the combined volume of the malignant tumours.

“Patients with the highest ctDNA levels at the time of lymphoma diagnosis had the poorest survival probability,” explains MD and PhD student Leo Meriranta.

At the same time, changes in ctDNA concentration during therapy reflected treatment responses in that the patients whose lymphoma was unaffected by the treatment were distinguished from other patients by the ctDNA analyses carried out using the follow-up blood samples.

The researchers also investigated the structural features of ctDNA and found that DNA fragments originating in the lymphoma were shorter in length compared to DNA fragments derived from healthy tissue.

By utilising machine learning, the researchers demonstrated that differences in the length of DNA fragments can be used to predict, for example, patients’ response to treatment.

“This finding opens up new avenues for studying circulating tumour DNA,” Meriranta confirms.

In the future, the findings can serve as a basis for increasingly accurate lymphoma diagnoses and the classification of patients into different groups for trials of novel therapies, which are key to identifying increasingly effective treatment options.

Towards increasingly tailored care

“In light of the findings, the methods available for targeting therapies in aggressive lymphomas are insufficient, while those used to measure the efficiency of therapies are inaccurate. This can expose patients to overtreatment and unnecessary adverse effects and make it difficult to come up with therapies tailored to individual patients,” Sirpa Leppä notes.

According to Leppä, ctDNA analyses will in the future revolutionise cancer diagnostics and clinical decision-making, but further research on the benefits of the findings is needed before ctDNA analyses of blood samples will become part of routine examinations for cancer patients.

Original article: Meriranta L, Alkodsi A, Pasanen A, Lepistö M, Mapar P, Blaker YN, Jørgensen JM, Karjalainen-Lindsberg ML, Fiskvik I, Mikalsen LTG, Autio M, Björkholm M, Jerkeman M, Fluge Ø, Brown P, Jyrkkiö S, Holte H, Pitkänen E, Ellonen P, Leppä S. Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma. Blood. doi: 10.1182/blood.2021012852. PMID: 34932792

The project was funded primarily by the Academy of Finland, HUS, the iCAN Digital Precision Cancer Medicine Flagship, the Sigrid Jusélius Foundation and the Cancer Society of Finland.