TY  - JOUR
A1  - Zhou, Xiang
A1  - Flüchter, Patricia
A1  - Nickel, Katharina
A1  - Meckel, Katharina
A1  - Messerschmidt, Janin
A1  - Böckle, David
A1  - Knorz, Sebastian
A1  - Steinhardt, Maximilian Johannes
A1  - Krummenast, Franziska
A1  - Danhof, Sophia
A1  - Einsele, Hermann
A1  - Kortüm, K. Martin
A1  - Rasche, Leo
T1  - Carfilzomib based treatment strategies in the management of relapsed/refractory multiple myeloma with extramedullary disease
JF  - Cancers
N2  - Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.
KW  - carfilzomib
KW  - extramedullary disease
KW  - multiple myeloma
KW  - relapse
KW  - refractory
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203704
SN  - 2072-6694
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Bai, Tao
A1  - Meckel, Katharina
A1  - Song, Jun
A1  - Jin, Yu
A1  - Kortüm, Martin K.
A1  - Eisele, Hermann
A1  - Hou, Xiaohua
A1  - Rasche, Leo
T1  - COVID-19 infection in patients with multiple myeloma: a German-Chinese experience from Würzburg and Wuhan
JF  - Annals of Hematology
N2  - No abstract available.
KW  - COVID-19
KW  - patients with multiple myeloma
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235108
SN  - 0939-5555
VL  - 100
ER  - 
TY  - JOUR
A1  - Steinhardt, M. J.
A1  - Wiercinska, E.
A1  - Pham, M.
A1  - Grigoleit, G. U.
A1  - Mazzoni, A.
A1  - Da-Via, M.
A1  - Zhou, X.
A1  - Meckel, K.
A1  - Nickel, K.
A1  - Duell, J.
A1  - Krummenast, F. C.
A1  - Kraus, S.
A1  - Hopkinson, C.
A1  - Weissbrich, B.
A1  - Müllges, W.
A1  - Stoll, G.
A1  - Kortüm, K. M.
A1  - Einsele, H.
A1  - Bonig, H.
A1  - Rasche, L.
T1  - Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes
JF  - Journal of Translational Medicine
N2  - Background 
Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. 

Methods 
To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. 

Results 
Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. 

Conclusion 
We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.
KW  - Myeloma
KW  - JCV
KW  - Prodigy
KW  - CCS
KW  - PML
KW  - Donor lymphocytes
KW  - Adaptive cell transfer
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229307
VL  - 18
ER  -