Hareth Nahi 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.
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.
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma.
Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Attal M, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Chiu C, Wang J, Van Rampelbergh R, Uhlar CM, Kobos R, Qi M, Usmani SZ,
N Engl J Med 2019 05;380(22):2104-2115
Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma.
Usmani SZ, Nahi H, Mateos MV, van de Donk NWCJ, Chari A, Kaufman JL, Moreau P, Oriol A, Plesner T, Benboubker L, Hellemans P, Masterson T, Clemens PL, Luo M, Liu K, San-Miguel J
Blood 2019 08;134(8):668-677
A Pilot, Exploratory, Randomized, Phase II Safety Study Evaluating Tumor Cell Mobilization and Apheresis Product Contamination in Patients Treated with Granulocyte Colony-Stimulating Factor Alone or Plus Plerixafor.
Nahi H, Celanovic M, Liu Q, Lund J, Peceliunas V
Biol Blood Marrow Transplant 2019 01;25(1):34-40
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P,
N Engl J Med 2016 10;375(14):1319-1331
Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma.
Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, Sasser AK, Axel A, Feng H, Uhlar CM, Wang J, Khan I, Ahmadi T, Nahi H
Blood 2016 07;128(1):37-44
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al
N. Engl. J. Med. 2015 Sep;373(13):1207-19