TY  - JOUR
A1  - Dahlhoff, Julia
A1  - Manz, Hannah
A1  - Steinfatt, Tim
A1  - Delgado-Tascon, Julia
A1  - Seebacher, Elena
A1  - Schneider, Theresa
A1  - Wilnit, Amy
A1  - Mokhtari, Zeinab
A1  - Tabares, Paula
A1  - Böckle, David
A1  - Rasche, Leo
A1  - Martin Kortüm, K.
A1  - Lutz, Manfred B.
A1  - Einsele, Hermann
A1  - Brandl, Andreas
A1  - Beilhack, Andreas
T1  - Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression
JF  - Leukemia
N2  - Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4\(^{+}\)FoxP3\(^{+}\) regulatory T cells (Tregs) are highly abundant amongst CD4\(^{+}\) T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.
KW  - Multiple myeloma
KW  - transient regulatory T-cell targeting
KW  - immune control
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271787
SN  - 1476-5551
VL  - 36
IS  - 3
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Ruckdeschel, Anna
A1  - Peter, Jessica
A1  - Böckle, David
A1  - Hornburger, Hannah
A1  - Danhof, Sophia
A1  - Steinhardt, Maximilian Johannes
A1  - Heimeshoff, Larissa
A1  - Einsele, Hermann
A1  - Kortüm, Klaus Martin
A1  - Rasche, Leo
T1  - Salvage therapy with "Dara-KDT-P(A)CE" in heavily pretreated, high-risk, proliferative, relapsed/refractory multiple myeloma
JF  - Hematological Oncology
N2  - The multi-agent therapy “VDT-PACE” represents an established regimen in relapsed/refractory multiple myeloma (RRMM). Here, we report on our experience with a “modified VDT-PACE” incorporating new generation anti-MM agents daratumumab and carfilzomib (“Dara-KDT-P(A)CE”). We retrospectively analyzed 38 patients with RRMM treated with “Dara-KDT-P(A)CE”. The median age was 62 (range 45–82) years, and the patients were heavily pretreated with a median of 5 (range 2–12) prior lines of therapy. Twenty-one (55%) patients suffered from penta-refractory MM. High-risk cytogenetics was present in 31 (81%) patients. The patients received a median of 2 (range 1–10) cycles of this therapy, and the overall response rate (ORR) was 70%. Patients with penta-refractory MM and high-risk cytogenetics showed similar ORR of 65% and 79%, respectively. The median progression-free survival (PFS) and overall survival were 4.1 (95% CI 2.7–5.4) and 8.4 (95% CI 6.7–10.0) months, respectively. Patients with lactate dehydrogenase >250 IU/L showed significantly shorter PFS in comparison with others patients (p = 0.006). We used this regimen as bridging therapy prior to chimeric antigen receptor T-cell infusion in four patients. In conclusion, “Dara-KDT-P(A)CE” is an effective salvage therapy for patients with heavily pretreated, multi-refractory, high-risk RRMM lacking alternative options.
KW  - Dara-KDT-P(A)CE
KW  - multiple myeloma
KW  - refractory
KW  - salvage
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257495
VL  - 40
IS  - 2
ER  -