Hodgkin lymphoma is a malignant B-cell lymphoma that is characterized by numerous genetic aberrations in multiple signaling pathways. After applying current therapy regimens, most patients achieve a cure – however, numerous early and late toxicities occur as part of the therapy and in the event of a recurrence, the prognosis is unfavorable. In a joint study, scientists developed the Clinic I for Internal Medicinethe German Hodgkin Study Group and the Translational tumor genetics and immunotherapy working group at the University Hospital of Cologne With the help of sequencing circulating tumor DNA, a biological classification of Hodgkin’s lymphoma is now available, which enables an improved prognosis assessment. The results were published in the renowned Journal of Clinical Oncology.
In Hodgkin’s lymphoma, the tumor tissue only consists to a small extent of the Hodgkin-Reed-Sternberg cells that are characteristic of this tumor – the majority is taken up by cells of the immune system. The genetic characterization of Hodgkin lymphoma from tumor material is therefore technically difficult. Sequencing circulating tumor DNA represents an alternative and has been successfully used for this purpose. The study used biomaterial from more than 250 patients who were treated as part of studies by the German Hodgkin Study Group.
After the analysis, the Cologne scientists were able to describe three subtypes of Hodgkin’s lymphoma: an inflammatory subtype with a tumor microenvironment that impairs the body’s immune response (Inflammatory Immune Escape HL), a subtype with an association with viral infections and chronic inflammation (Virally-driven HL ) and a third subtype, which is characterized by the presence of numerous point mutations characteristic of Hodgkin’s lymphoma (oncogene-driven HL). In a separate clinical validation, this new biological classification of Hodgkin’s lymphoma could be tested under conditions that are realistic for clinical routine. There was a significant difference in progression-free survival between the three subtypes.
Dr. Jan-Michel Heger, specialist at Clinic I for Internal Medicine, and alongside Dr. Laman Mammadova and Julia Mattlener, also from Clinic I, one of the three first authors of the study on the importance for the therapy of patients with Hodgkin’s lymphoma: “The findings of the study will allow an evaluation of a therapy intensity adapted to the individual risk profile in the future.” Priv.-Doz. Dr. Dr. Sven Borchmann, head of the working group for translational tumor genetics and immunotherapy and last author of the study, adds: “In particular, the combination of the prognostic significance of the new biological classification with a follow-up of the treatment response by sequencing the circulating tumor DNA during therapy, the so-called MRD determination , could enable largely individualized therapy for patients with Hodgkin lymphoma in the future.”
Publication:
Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With Hodgkin Lymphoma. Jan-Michel Heger, Laman Mammadova, Julia Mattlener, Sophia Sobesky, Melita Cirillo, Janine Altmüller, Elisabeth Kirst, … and Sven Borchmann. J Clin Oncol 2024.
