Myeloma group
The key question in our research through the years has been and still is to identify why some patients with Multiple Myeloma (MM) a quiet disease with good long-term survival have, while others have a more aggressive disease that does not respond to treatment and have a very dismal survival.
About our research
Our hypothesis is that correct combination of available treatment modalities and addition of new therapies will improve results and perhaps cure a fraction of patients. We also investigate new treatment methods that can have effect where ordinary therapy fails, try to understand the mechanisms of action and identify the group of patients who would benefit most from the drug or treatment method. The plasma cell diseases group have interest in identifying prognostic parameters, chromosomal aberrations/genes on specific chromosomes as well as perform a genomewide analysis of disease associations and reducing side effects of immune-therapy.
Our group is divided in four main teams:
A)The team at the clinical: Real word data analysis of prognostic parameters related to specific therapies in patients with MM and differences in outcome.
B)The immune-therapy lab: Improvement of current-generation tumor-targeting strategies to enhance efficacy and reduce adverse events in NK and CAR-T cell-mediated therapies in multiple myeloma, conducting immunotherapy trials, in collaboration with Evren Alici.
C)The molecular biology lab: To understand the genetic characterization of MM at the diagnosis and to identify genes of importance in the progressive disease over time.
D)Clinical trial team: conducting clinical trials with the aim of enhancing outcome.
Main achievements and discoveries
Our real word data have produced several projects through the years, both alone and in collaboration with: The Swedish/Nordic myeloma group and the international myeloma working group (IMWG). These projects have been the background leading to regular enhancement of the treatment program in MM patient, resulting in three doubling of the survival during the last 10-15 years.
Since the last decade we are in a close collaboration with the immune-therapy- group, we have worked extensively on clinical grade expansion, activation and gene modification of primary human NK cells from healthy donors and patients with MM. This collaboration resulted in a newly finished autologous NK cell therapy clinical trials for MM patients. Within the molecular biology lab-/chromosome lab we have succeeded in defining several chromosomes/genes that impact the prognosis of MM patients, such as del.8p21 and add 1q. Our future projects aim to define genes responsible to progression during the disease.
At the clinic, Hareth Nahi is the lead of the clinical trial team. Until today Hareth has been the coordinating investigator of 70 international clinical trials, eight of them so called first in human trials. Twenty patients of the first thirty patients who were treated with anti-CD38 (Daratumumab) were from our site. Currently we are participating in a first in human trial using a Humanized BCMA / CD3 Antibody.
Acting Principal Investigator
Evren Alici
M.D., PhD. Principal researcherJunior Principal Investigator
Johan Lund
M.D., PhD. Senior consultant. Affiliated to researchTeam leaders
Katarina Uttervall
M.D., PhD. Affiliated to research.Arnika Kathleen Wagner
PhD. Assistant professorGroup members
Muhammad Kashif
PhD. Research specialistVincent Luong
M.D. Affiliated to research.Ann Wallblom
Lab Manager, Biomedical AnalystAnnette Öster Fernström
PhD. Coordinator for the Myeloma group. PA for Johan Lund.Affiliated members
Gabriel Afram
M.D., PhD. Affiliated to research.Gösta Gahrton
M.D., PhD. Professor and mentorHareth Nahi
M.D., PhD. Affiliated to researchAlumni
Göran Wålinder, MD PhD. Dissertation 2022: Plasma cell malignancies in Sweden: Subgroup descriptions and regional outcomes for multiple myeloma.
Selected publications
- Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy. Susek KH, Schwietzer YA, Karvouni M, Gilljam M, Keszei M, Hussain A, Lund J, Kashif M, Lundqvist A, Ljunggren HG, Nahi H, Wagner AK, Alici E. Cancer Immunol Immunother. 2022 Nov 10. Online ahead of print.
- Adaptive single-KIR+NKG2C+ NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia. Haroun-Izquierdo A, Vincenti M, Netskar H, van Ooijen H, Zhang B, Bendzick L, Kanaya M, Momayyezi P, Li S, Wiiger MT, Hoel HJ, Krokeide SZ, Kremer V, Tjonnfjord G, Berggren S, Wikström K, Blomberg P, Alici E, Felices M, Önfelt B, Höglund P, Valamehr B, Ljunggren HG, Björklund A, Hammer Q, Kveberg L, Cichocki F, Miller JS, Malmberg KJ, Sohlberg E. J Immunother Cancer. 2022 Nov;10(11):e005577.
- Regional differences in treatment and outcome for myeloma patients in Sweden: A population based Swedish myeloma register study. Wålinder G, Genell A, Juliusson G, Svensson R, Santamaria AI, Crafoord J, Carlson K, Knut-Bojanowska D, Veskovski L, Lauri B, Lund J, Turesson I, Hansson M, Blimark CH, Nahi H. Cancer Rep (Hoboken). 2022 Nov;5(11):e1614.
- Autologous NK cells as consolidation therapy following stem cell transplantation in multiple myeloma. Nahi H, Chrobok M, Meinke S, Gran C, Marquardt N, Afram G, Sutlu T, Gilljam M, Stellan B, Wagner AK, Blomberg P, Holmqvist PH, Walther-Jallow L, Mellström K, Liwing J, Gustafsson C, Månsson R, Klimkowska M, Gahrton G, Lund J, Ljungman P, Ljunggren HG, Alici E. Cell Rep Med. 2022 Jan 28;3(2):100508.
- Low dose venetoclax as a single agent treatment of plasma cell malignancies harboring t(11;14). Nahi H, Kashif M, Klimkowska M, Karvouni M, Wallblom A, Gran C, Hauenstein J, Frengen N, Gustafsson C, Afram G, Uttervall K, Lund J, Månsson R, Wagner AK, Alici E. Am J Hematol. 2021 Aug 1;96(8):925-933.
- Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D. Sayitoglu EC, Georgoudaki AM, Chrobok M, Ozkazanc D, Josey BJ, Arif M, Kusser K, Hartman M, Chinn TM, Potens R, Pamukcu C, Krueger R, Zhang C, Mardinoglu A, Alici E, Temple HT, Sutlu T, Duru AD. 2020. Front Immunol 11:40.
- Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma. Nahi H, Chrobok M, Gran C, Lund J, Gruber A, Gahrton G, Ljungman P, Wagner AK, Alici E. PLoS One. 2019 Feb 13;14(2):e0211927.
- Advances in clinical NK cellstudies: Donor selection, manufacturing and quality control. Koehl U, Kalberer C, Spanholtz J, Lee DA, Miller JS, Cooley S, Lowdell M, Uharek L, Klingemann H, Curti A, Leung W, Alici E. Oncoimmunology. 2015 Nov 11;5(4):e1115178.