NCT Research

CCRP CLL & Lymphoma

The CLL/Lymphoma Program combines clinical and research expertise focusing on the understanding of the pathogenesis of CLL and lymphoma. We have established a systems medicine program that integrates systematic functional assays, multi-omic profiling, bioinformatic analysis, mathematical modeling and setup towards a clinical exploitation. The basis of the program is a platform to map patient specific pathway activity and drug sensitivity of their primary tumor cells ex-vivo. By comparing drug responses across patients with detailed molecular characterization (e.g. whole exome- and RNA-sequencing) and the clinical parameters, we obtain a rich set of associations of drug sensitivity with biology, biomarkers and outcome.

Members of the program take a leading role in the GCLLSG, EBMT, and Helmholtz and BMBF-funded research consortia and the “Early trial Network”. The group has been instrumental in developing clinical guidelines.

CCRP CLL & Lymphoma
 

PD Dr. Dietrich
Internal Medicine V

 
 
 

Dr. Julia Meissner
Dept. of Internal Medicine V: Hematology, Oncology and Rheumatology, Heidelberg University Hospital

Prof. Peter Dreger
Dept. of Internal Medicine V: Hematology, Oncology and Rheumatology, Heidelberg University Hospital

Prof. Michael Schmitt
Dept. of Internal Medicine V: Hematology, Oncology and Rheumatology, Heidelberg University Hospital

Prof. Tim Weber
Dept. of Radiology, Heidelberg University Hospital

Prof. Gunhild Mechtersheimer
Dept. of Pathology, Heidelberg University Hospital

Dr. Martina Seiffert
Division of Molecular Genetics, German Cancer Research Center

Prof. Frank Ückert
Division of Medical Informatics for Translational Oncology, German Cancer Research Center

Scientific Aims:

  • Practice-changing clinical concepts for lymphoma patients (Dietrich NEJM 2012)
  • Develop artificial intelligence solutions to support treatment and diagnostic clinical procedures
  • Set up large scale pre-clinical drug screen program to support personalized treatment decisions
  • Understand how molecular features impact response and survival in lymphoma and CLL.
  • Create new diagnostic and therapeutic options for patients with CLL and lymphoma
  • Develop biomarker driven interventional early phase clinical trials
  • Phase I clinical trial center for innovative trials

Aims Clinical Care:

  • State of the art care for patients suffering from CLL and lymphoma including allogeneic stem cell transplantation and CAR T-cell therapy
  • Develop strategic partnerships with pharma industry and run industry initiated biomarker driven early phase clinical trials.
  • Develop individualized treatment concepts (molecularly informed personalized medicine)
  1. Dietrich S, Glimm H, Andrulis M, von Kalle C, Ho AD, Zenz T. BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med. 2012 May 24;366(21): 2038-40.
     
  2. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial.
    von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. J Clin Oncol. 2012 Mar 20;30(9):907-13. doi: 10.1200/JCO.2011.38.5807. Epub 2012 Jan 23.
     
  3. Haploidentical stem cell transplantation for patients with lymphoma: a position statement from the Lymphoma Working Party-European Society for Blood and Marrow Transplantation.
    Sascha Dietrich, Peter Dreger, Olivier Hermine, Chara Kyriakou, Silvia Montoto, Steve Robinson, Norbert Schmitz, Harry C Schouten, Anna Sureda & Alina Tanase. Bone Marrow Transplantation (2019). PMID: 31150019 DOI: 10.1038/s41409-019-0583-4.
     
  4. IGF1R as druggable target mediating PI3K-δ inhibitor resistance in a murine model of chronic lymphocytic leukemia.
    Scheffold A, Jebaraj BMC, Tausch E, Bloehdorn J, Ghia P, Yahiaoui A, Dolnik A, Blätte TJ, Bullinger L, Dheenadayalan RP, Li L, Schneider C, Chen SS, Chiorazzi N, Dietrich S, Seiffert M, Tannheimer S, Döhner H, Mertens D, Stilgenbauer S. Blood. 2019 Aug 8;134(6):534-547. doi: 10.1182/blood.2018881029. Epub 2019 Apr 22. PMID: 31010847.
     
  5. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.
    Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, Gladstone DE, le Coutre P, Dietrich S, Gotic M, Larratt L, Offner F, Schiller G, Swords R, Bacon L, Bocchia M, Bouabdallah K, Breems DA, Cortelezzi A, Dinner S, Doubek M, Gjertsen BT, Gobbi M, Hellmann A, Lepretre S, Maloisel F, Ravandi F, Rousselot P, Rummel M, Siddiqi T, Tadmor T, Troussard X, Yi CA, Saglio G, Roboz GJ, Balic K, Standifer N, He P, Marshall S, Wilson W, Pastan I, Yao NS, Giles F. Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 20.
     
  6. Drug-perturbation-based stratification of blood cancer.
    Dietrich S, Oleś M, Lu J, Sellner L, Anders S, Velten B, Wu B, Hüllein J, da Silva Liberio M, Walther T, Wagner L, Rabe S, Ghidelli-Disse S, Bantscheff M, Oleś AK, Słabicki M, Mock A, Oakes CC, Wang S, Oppermann S, Lukas M, Kim V, Sill M, Benner A, Jauch A, Sutton LA, Young E, Rosenquist R, Liu X, Jethwa A, Lee KS, Lewis J, Putzker K, Lutz C, Rossi D, Mokhir A, Oellerich T, Zirlik K, Herling M, Nguyen-Khac F, Plass C, Andersson E, Mustjoki S, von Kalle C, Ho AD, Hensel M, Dürig J, Ringshausen I, Zapatka M, Huber W, Zenz T.
     
  7. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial.
    Krämer I, Stilgenbauer S, Dietrich S, Böttcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Döhner H, Dreger P. Blood. 2017 Sep 21;130(12):1477-1480. doi: 10.1182/blood-2017-04-775841. Epub 2017 Jul 17. No abstract available.
     
  8. Outcome and prognostic factors in patients with mantle-cell lymphoma relapsing after autologous stem-cell transplantation: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT).
    Dietrich S, Boumendil A, Finel H, Avivi I, Volin L, Cornelissen J, Jarosinska RJ, Schmid C, Finke J, Stevens WB, Schouten HC, Kaufmann M, Sebban C, Trneny M, Kobbe G, Fornecker LM, Schetelig J, Kanfer E, Heinicke T, Pfreundschuh M, Diez-Martin JL, Bordessoule D, Robinson S, Dreger P. Ann Oncol. 2014 May;25(5):1053-8. doi: 10.1093/annonc/mdu097. Epub 2014 Feb 27.
     
  9. Continued response off treatment after BRAF inhibition in refractory hairy cell leukemia.
    Dietrich S, Hüllein J, Hundemer M, Lehners N, Jethwa A, Capper D, Acker T, Garvalov BK, Andrulis M, Blume C, Schulte C, Mandel T, Meissner J, Fröhling S, von Kalle C, Glimm H, Ho AD, Zenz T. J Clin Oncol. 2013 Jul 1;31(19):e300-3. doi: 10.1200/JCO.2012.45.9495. Epub 2013 May 20. No abstract available. PMID: 23690412.

Specific Treatment Options

  • CAR-T cell therapies, bispecific antibodies, allogeneic stem cell transplantation