Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. The clinical course of CLL is highly heterogeneous. During the last decade, the treatment options for CLL has developed from single and combination chemotherapy to immune-chemotherapy and targeted agents, thereby significantly improving the outcome for patients. A more comprehensive approach to immune complications, treatment outcome, and disease outcome among patients with CLL is warranted.
By capture of paraclinical, clinical and demographic data along with genetic and functional characterization of primary CLL cells in our laboratory, we assemble multidimensional data on patients with CLL through the PERSIMUNE platform. With this unique three-pronged setup (translational research, clinical trials and registry based “real world evidence”), we explore patterns predictive of treatment outcome, infectious complications and disease outcome upon specific treatment.
By development of machine learning based algorithms in collaboration with DTU Compute, we aim for individually tailored CLL specific treatment and supportive care in CLL. By developing investigator-initiated, inter-group studies in collaboration between the Nordic, Hovon and German CLL study groups, we assure assessment of novel combination treatments for CLL and form a basis for testing individually tailored treatment in future clinical trials
Key results
With the B-cell receptor pathway as the core, our group has been part of a paradigm shift for treatment of CLL with novel targeted therapies developed also for patients with the most dismal outcome due to TP53 aberrations. With the parallel development of translational and experimental studies based on our own unique CLL biobank, CLL epidemiology studies based on the comprehensive Danish National CLL database, and CLL clinical inter-group trials, we have created a unique position for development of not only prognostic algorithms but also tailored novel treatment regimens, which can be prospectively validated via investigator-initiated clinical trials.
People
Carsten Utoft Niemann, MD, PhD, Principal Investigator, Head of Leukemia Laboratory
Christian H. Geisler, Prof Emeritus, MD
Clinical scientists
Caspar da Cunha-Bang, MD, PhD
Fie Juhl Vojdeman, MD, PhD, currently Dept of Biochemistry, Bispebjerg Hospital
Ph.D. candidates
Michael Asger Andersen, MD
Christian Brieghel, MD
Rebecca XMS Valentin, MD
Pregraduate students
Casper Eriksen, Engineering
Laboratory staffLone Bredo Pedersen, Scientific laboratory technician
Emil Jakobsen, laboratory technician, in collaboration with the clinical trial unit
Trine Enevoldsen, laboratory technician, in collaboration with the clinical trial unit
Collaborators
- Finn Cilius Nielsen, Prof, MD, PhD, Center for Genomic Medicine, Righospitalet.
- Jens Lundgren, Prof, MD, PhD, PERSIMUNE, Department of Infection Medicine, Rigshospitalet.
- Henrik Hjalgrim, MD, PhD, SSI, Statens Serum Institut.
- Jan Larsen, Prof, MSc, DTU, DTU Compute, Cognitive Science.
- Matthew S. Davids, MD, PhD, Dana-Farber Cancer Institute, MA, USA
- Adrian Wiestner, MD, PhD, NHLBI, National Institutes of Health, MD, USA
- Arnon P Kater, Prof, MD, PhD, AMC, HOVON study group, Amsterdam, the Netherlands.
- Michael Hallek, Prof, MD, PhD, University of Cologne, German CLL study group, Cologne, Germany
- Nordic CLL study group
Clinical Trials
Chronic lymphocytic leukemia:
- Vision trial (upcoming , quarter 1, 2017), founding member
- CLL-GAIA/CLL13 trial (recruiting), founding member
- CLL14 (completed)
- HOVON68 (completed), founding member
- MURANO (completed)
- PROLONG (completed), founding member
Mantle Cell Lymphoma:
- Triangle (recruiting), responsible for laboratory analyses
- Philemon (completed), responsible for laboratory analyses
Selected publications
- Niemann CU and Christiansen I: Kronisk Lymfoproliferative Sygdomme, kapitel i Hæmatologi i klinisk praksis (Overgaard U and Birgens H ed.), Munksgaard 2016. In Press.
- Herman SEM, Montraveta A, Niemann CU, Mora-Jensen H, Gulrajani M, Krantz F, Mantel R, Smith LL, Harrington B, Colomer D, Covey T, Byrd JC, Izumi R, Kaptein A, Urlich R, Johnson AJ, Lannutti BJ, Wiestner A, and Woyach JA: The Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia, Clin Cancer Res. 2016 nov, epub ahead of print DOI: 10.1158/1078-0432.CCR-16-0463.
- da Cunha-Bang C, Simonsen J, Rostgaard K, Geisler C, Hjalgrim H and Niemann CU: Improved survival for Patients diagnosed with Chronic Lymphocytic Leukemia in the era of Chemo-immunotherapy - a Danish Population Based Study of 10455 patients, Blood Cancer J. 2016 Nov 11;6(11):e499. doi: 10.1038/bcj.2016.105.
- da Cunha-Bang C, Geisler CH, Enggaard L, Poulsen CB, de Nully Brown P, Frederiksen H, Bergman O, Pulczynski E, Pedersen R, Nielsen L, Christiansen I, Niemann CU: The Danish National CLL Registry, Clinical Epidemiology, 2016 Oct 25;8:561-565.
- da Cunha-Bang C, Christiansen I, Niemann CU: The International prognostic Index for patients with chronic lymphocytic leukemia (CLL-IPI) applied in a population-based cohort. Blood. 2016 Oct 27;128(17):2181-2183.
- Sutton LA, Young E, Baliakas P, Hadzidimitriou A, Moysiadis T, Plevova K, Rossi D, Kminkova J, Stalika E, Pedersen LB, Malcikova J, Agathangelidis A, Davis Z, Mansouri L, Scarfò L, Boudjoghra M, Navarro A, Muggen AF, Yan XJ, Nguyen-Khac F, Larrayoz M, Panagiotidis P, Chiorazzi N, Niemann CU, Belessi C, Campo E, Strefford JC, Langerak AW, Oscier D, Gaidano G, Pospisilova S, Davi F, Ghia P, Stamatopoulos K, Rosenquist R: Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. Haematologica. 2016 Aug;101(8):959-67
- Andersen MA, Andersen MK, Vojdeman FJ, de Nully Brown P, Geisler CH, Bjerrum OW, Niemann CU: Hypogammaglobulinemia in Newly Diagnosed Chronic Lymphocytic Leukemia is a predictor of early death. Leuk Lymphoma. 2016 Jul;57(7):1592-9. doi: 10.3109/10428194.2016.1142082.
- Niemann CU, Herman SEMH, Maric I, Gomez-Rodriguez J, Biancotto A, Chang BY, Martyr S, Stetler-Stevenson M, Yuan C, Calvo KR, Braylan RC, Valdez J, Lee YS, Wong DH, Jones J, Sun CCL, Marti GE, Farooqui MZ, Wiestner A: Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib – findings from an investigator initiated phase 2 study, Clin Cancer Res. 2016 Apr 1;22(7):1572-82. doi: 10.1158/1078-0432.CCR-15-1965.
- Skarzynski M, Niemann CU, Lee YS, Martyr S, Maric I, Salem D, Stetler-Stevenson M, Marti GE, Calvo KR, Yuan CM, Valdez J, Soto S, Farooqui MZH, Herman SEM, Wiestner A: Inter¬actions between ibrutinib and anti-CD20 antibodies; competing effects on the outcome of combi¬nation therapy, Clin Cancer Res. 2016 Jan 1;22(1):86-95. doi: 10.1158/1078-0432.CCR-15-1304. Lipsky AH, Farooqui MZH, Tian X, Martyr S, Cullinane AM, Nghiem K, Sun C, Valdez J, Niemann CU, Herman SEM, Saba N, Soto S, Marti G, Uzel G, Holland SM, Lozier JN, Wiestner A: Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib, Haematologica. 2015 Dec;100(12):1571-8. doi: 10.3324/haematol.2015.126672.
- Farooqui MZH, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, Herman SEM, Tian X, Marti G, Soto S, Hughes TE, Jones J, Lipsky A, Pittaluga S, Stetler-Stevenson M, Yuan C, Lee YS, Pedersen LB, Geisler CH, Calvo KR, Arthur DC, Maric I, Childs R, Young NS, Wiestner A: Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial, Lancet Oncol. 2015 Feb;16(2):169-76. doi: 10.1016/S1470-2045(14)71182-9.
- Herman SEM*, Niemann CU*, Farooqui M*, Jones J, Mustafa RZ, Lipsky A, Saba N, Martyr S, Soto S, Valdez J, Gyamfi JA, Maric I, Calvo KR, Pedersen LB, Geisler CH, Liu D, Marti GE, Aue G, Wiestner A: Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study. Leukemia. 2014 Nov;28(11):2188-96. doi: 10.1038/leu.2014.122. *shared 1st authors.
- Niemann CU, Geisler CH: Målrettet behandling af lymfoproliferativ sygdom: Kinasehæmmere og Bcl-2 hæmmere, Ugeskr Læger 2014;176:V66229.
- Niemann CU: Målrettet behandling af kronisk lymfatisk leukæmi, Statusartikel, Ugeskrift for Læger, 2014, April, epub ahead of print, Ugeskr Læger 2014;176:V11130682.
- Niemann CU, Polliack A, Hutchings M: Suspected Richter transformation: positron emission tomography/computed tomography tells us who should have a biopsy and where. Leuk Lymphoma. 2014 Feb;55(2):233-4.
- Niemann CU, Wiestner A: B-cell receptor signaling as a driver of lymphoma development and evolution. Semin Cancer Biol. 2013 Dec;23(6):410-21.
- Niemann CU, Jones J, Wiestner A: Towards targeted therapy of Chronic Lymphocytic Leukemia, book chapter in: Advances in Chronic Lymphocytic Leukemia, in the series: Advances in Experimental Medicine and Biology, 2013;792: 259-91.