Chronic Lymphocytic Leukemia Laboratory

Combining translational, epidemiological and clinical research to develop individually tailored supportive care and CLL specific treatment.

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 CLL Laboratory, Chair of Nordic CLL Study Group

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
Rudi Agius Post. Doc. 
Christian Brieghel, MD, PhD: Herlev Hospital

Ph.D. candidates
Michael Asger Andersen, MD
Rebecca XMS Valentin, MD
Rebecka Svanberg, MD 
Emelie Hamotal Curovic Rotbain, MD
Per Ishøy Nielsen, MD
Mehdi Parvis, upcoming  PhD student

Pregraduate students
Kathrine Aarup
Noomi Vainer

Laboratory staff
Lone Bredo Pedersen, Scientific laboratory technician
Trine Enevoldsen, laboratory technician, in collaboration with the clinical trial unit
Jane Hinrichsen, laboratory technician, in collaboration with the clinical trial unit
Betina Gall, laboratory technician, in collaboration with the clinical trial unit
Louise Le Dous, laboratory staff
Marianne Blirup Jensen, laboratory staff

Assistant
Mette Højmose Thrane

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, DMSc, SSI: Statens Serum Institut.
  • 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
  • Ole Winther, Prof, MSc: DTU, DTU Compute, Cognitive Science.
  • Anders Österborg Prof, MD: Nordic CLL study group: http://www.nordic-cll.org/
  • Richard Rosenquist Brandell Prof, MD: Nordic CLL study group: http://www.nordic-cll.org/
  • Sigrid Skånland, PhD: Department of Cancer Immunology, Oslo University Hospital

Clinical Trials

Chronic lymphocytic leukemia:

  • PreVent-ACaLL (recruiting), founding member, sponsor
  • Assure (recruting)
  • CLL17 (planned), founding member
  • HOVON158, Next Step trial (planned)
  • Vision HO141 trial (completed), founding member
  • GAIA CLL13 trial (completed), founding member
  • CLL3011 GLOW (completed), 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
  • Valeria (recruiting), responsible for laboratory analyses
  • Vision (recruiting), responsible for laboratory analyses

Videos

Selected publications


Niemann CU: Cost-effectiveness targeting CLL, Blood, in press

Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink A, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner C, Kreuzer K, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K: Fixed-duration venetoclax-obinutuzumab for patients with previously untreated chronic lymphocytic leukaemia: follow-up of efficacy and safety results from the multicentre, open-label, randomised, phase 3 CLL14 trial, Lancet Onc, in press

Aarup K, Rotbain EC, Enggaard L, Pedersen RS, Bergmann OJ, Thomsen RH, Frederiksen M, Frederiksen H, Nielsen T, Christiansen I, Andersen MA*, Niemann CU* (* co senior-authors): Real-World Outcomes for 205 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib, Eur J Hem, in press



Scarfò L, Chatzikonstantinou T, Rigolin GM, Quaresmini G, Motta M, Vitale C, Garcia-Marco JA, Hernández-Rivas JÁ, Mirás F, Baile M, Marquet J, Niemann CU, Reda G, Munir T, Gimeno E, Marchetti M, Quaglia FM, Varettoni M, Delgado J, Iyengar S, Janssens A, Marasca R, Ferrari A, Cuéllar-García C, Itchaki G, Špaček M, De Paoli L, Laurenti L, Levin MD, Lista E, Mauro FR, Šimkovič M, Van Der Spek E, Vandenberghe E, Trentin L, Wasik-Szczepanek E, Ruchlemer R, Bron D, De Paolis MR, Del Poeta G, Farina L, Foglietta M, Gentile M, Herishanu Y, Herold T, Jaksic O, Kater AP, Kersting S, Malerba L, Orsucci L, Popov VM, Sportoletti P, Yassin M, Pocali B, Barna G, Chiarenza A, Dos Santos G, Nikitin E, Andres M, Dimou M, Doubek M, Enrico A, Hakobyan Y, Kalashnikova O, Ortiz Pareja M, Papaioannou M, Rossi D, Shah N, Shrestha A, Stanca O, Stavroyianni N, Strugov V, Tam C, Zdrenghea M, Coscia M, Stamatopoulos K, Rossi G, Rambaldi A, Montserrat E, Foà R, Cuneo A, Ghia P: COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020 doi: 10.1038/s41375-020-0959-x










Hleuhel MH, Ben-Dali Y, Da Cunha-Bang C, Brieghel C, Clasen-Linde E, Niemann CU, Andersen MA: Risk factors associated with Richter's transformation in patients with chronic lymphocytic leukaemia: protocol for a retrospective population-based cohort study. BMJ Open. 2019 Mar 3;9(3):e023566. doi: 10.1136/bmjopen-2018-023566




Bidrag (CLL og lymfoproliferative sygdomme) til Kap. 34: Blodsygdomme i Medicinsk Kompendium (19. udgave) red. af Jesper Hastrup, Hendrik Vilstrup og Ove Schaffalitzky, 2019, ISBN 978-87-628-1752-4









Niemann CU and Christiansen I: Kronisk Lymfoproliferative Sygdomme, kapitel i Hæmatologi i klinisk praksis (Overgaard U and Birgens H ed.), Munksgaard januar 2017

Niemann CU and Christiansen I: Kronisk Lymfoproliferative Sygdomme, kapitel i Hæmatologi i klinisk praksis (Overgaard U and Birgens H ed.), Munksgaard januar 2017

von-Tresckow J, Bahlo J, Niemann CU, Kater AP, Fink AM, Fischer K, Ritgen M, Kreuzer KA, Stilgenbauer S, van Oers R, Geisler CG, Hellek M, Eichhorst B: The GAIA (CLL13) trial – an international, randomized, four-arm study for first line treatment of physically fit CLL patients without del17p or TP53 mutation, Integr Cancer Sci Therap, 2017 doi: 10.15761/ICST.1000252 Volume 4(5): 1-2

Niemann CU and Christiansen I: Kronisk Lymfoproliferative Sygdomme, kapitel i Hæmatologi i klinisk praksis (Overgaard U and Birgens H ed.), Munksgaard 2016.

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, DOI: 10.1158/1078-0432.CCR-16-0463

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, 20Khac 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. Doi: 10.3324/haematol.2016.141812


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

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, 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







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