A biomarker-driven and risk-adapted interventional approach

Field of research

Biology, therapy, outcome prediction and response monitoring of T-cell lymphomas (TCL)

Brief background

TCL is a heterogeneous group of lymphoma entities accounting for 10% of all lymphomas. With the exception of ALK+ anaplastic TCL, their outcome is poor with 5-year progression-free and overall survival rates of 30% and 45%, respectively, making TCL one of the major areas of unmet need in lymphoma medicine.

Type of project

Investigator-initiated clinical trial combined with correlative biological studies and elaboration of new prognostic indices

Project title

A clinical trial evaluating a circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) approach and a randomized biomarker-driven post-induction maintenance in patients with newly diagnosed TCL of all entities, ages and frailty groups.

Clinical questions of the study

• Do classical prognostic factors combined with biological features allow for novel subtype-specific prognostic indices in TCL?
• Does ctDNA-based MRD monitoring improve response assessment and relapse prediction?
• Does a bioprofile-driven maintenance therapy in chemosensitive patients improve outcome?
• Does autologous hematopoietic stem cell transplant improve response quality in TCL?

Perspectives of the study

This trial aligns with internationally recognized crucial strategy goals in clinical cancer research:

• Tackle cancers with substantial unmet need’:  PTCL is a rare cancer with an annual incidence of 1-2 per 100,000 of the population and a 10-year prevalence of 4-5 per 100,000. Outcomes are generally poorer than in B-cell derived lymphomas, even for front-line treatment, making this disorder one of the major areas of unmet need in lymphoma medicine.
• Building our understanding of cancer’: The translational projects that form an integral part of this proposal are specifically aimed at this. Prospective gene expression profiling and mutation analysis will increase our imperfect understanding of the genetics of T-cell lymphoma and in particular whether such knowledge impacts on treatment outcomes. As T-cell lymphoma is a rare disease, this dataset will contribute substantially to the global understanding of this disease.
• Accelerate the translation of research into clinical practice’: The translational projects are aimed at trying to predict who, among PTCL patients, will benefit most from a biofeature-driven therapeutic approach and whether response assessment can be improved by the introduction of ctDNA measurements.
• Maintain a broad portfolio that maximizes patient benefit’: Answering the 3 main questions asked by the PANTHEON trial is likely to lead to practice changing discoveries. If so, this will be done on the basis of an academically driven broad inclusion platform across histological entities and clinical performances.

1. Specific knowledge on the biology of human TCL
2. Broad experience with molecular genetic analysis methods, incl. single cell analysis techniques
3. Good skills in ctDNA-related research and analysis methods
4. Well-established skills in biostatistical methods and bioinformatics
5. Some experience in clinical trials with correlative biological analyses

1. Broad experience in clinical research of  T-cell derived lymphoid malignancies
2. Internationally recognized expertise in designing and implementing clinical trials in T-cell lymphomas (TCL)
3. Extensive experience in translational research in TCL
4. Circulating tumour DNA in TCL
5. Single-cell molecular genetic analyses in TCL