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  - 
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  - Steinhardt, Maximilian Johannes
A1  - Zhou, Xiang
A1  - Krummenast, Franziska
A1  - Meckel, Katharina
A1  - Nickel, Katharina
A1  - Böckle, David
A1  - Messerschmidt, Janin
A1  - Knorz, Sebastian
A1  - Dierks, Alexander
A1  - Heidemeier, Anke
A1  - Lapa, Constantin
A1  - Einsele, Hermann
A1  - Rasche, Leo
A1  - Kortüm, Klaus Martin
T1  - Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma
JF  - International Journal of Immunopathology and Pharmacology
N2  - We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab (“Pom-PAD-Dara”), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.
KW  - CD38
KW  - MOR202
KW  - daratumumab
KW  - multiple myeloma
KW  - refractory
KW  - relapse
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236235
VL  - 34
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Dierks, Alexander
A1  - Kertels, Olivia
A1  - Samnick, Samuel
A1  - Kircher, Malte
A1  - Buck, Andreas K.
A1  - Haertle, Larissa
A1  - Knorz, Sebastian
A1  - Böckle, David
A1  - Scheller, Lukas
A1  - Messerschmidt, Janin
A1  - Barakat, Mohammad
A1  - Truger, Marietta
A1  - Haferlach, Claudia
A1  - Einsele, Hermann
A1  - Rasche, Leo
A1  - Kortüm, K. Martin
A1  - Lapa, Constantin
T1  - The link between cytogenetics/genomics and imaging patterns of relapse and progression in patients with relapsed/refractory multiple myeloma: a pilot study utilizing 18F-FDG PET/CT
JF  - Cancers
N2  - Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1–10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.
KW  - radiogenomics
KW  - 18F-FDG PET/CT
KW  - multiple myeloma
KW  - relapse
KW  - progression
KW  - pattern
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211157
SN  - 2072-6694
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Rasche, Leo
A1  - Kortüm, K. Martin
A1  - Danhof, Sophia
A1  - Hudecek, Michael
A1  - Einsele, Hermann
T1  - Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies
JF  - Frontiers in Immunology
N2  - In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their “last chance” and a “hope of cure”. However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.
KW  - CAR T cell
KW  - clinical trial
KW  - multiple myeloma
KW  - toxicity
KW  - pathophysiology
KW  - management
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219911
SN  - 1664-3224
VL  - 11
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Steinhardt, Maximilian J.
A1  - Grathwohl, Denise
A1  - Meckel, Katharina
A1  - Nickel, Katharina
A1  - Leicht, Hans‐Benno
A1  - Krummenast, Franziska
A1  - Einsele, Hermann
A1  - Rasche, Leo
A1  - Kortüm, Klaus M.
T1  - Multiagent therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab (“Pom‐PAD‐Dara”) in relapsed/refractory multiple myeloma
JF  - Cancer Medicine
N2  - Background
Even in the era of novel immunotherapies for multiple myeloma (MM), treatment of late‐stage relapsed/refractory (RR) patients remains challenging. The aim of our study was to analyze the efficacy and safety of the five‐drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab (“Pom‐PAD‐Dara”) in RRMM.


Methods
We retrospectively analyzed data of 56 patients with RRMM who received Pom‐PAD‐Dara between September 2016 and May 2019.


Results
Patients were heavily pretreated with a median of four prior lines of therapy, including autologous and allogenic stem cell transplant in 50 (89%) and six (11%) patients, respectively. The overall response rate (ORR) was 78% and we observed partial remission, very good partial remission, and complete remission in 27 (48%), 13 (23%) and four (7%) patients, respectively. Median progression‐free survival was 7 months (95% CI, 3.3‐10.7) and the median overall survival was not reached at 24 months. Adverse events grade ≥ 3 were observed 41 (73%) patients and included neutropenia (n = 28, 50%), anemia (n = 22, 39%), thrombocytopenia (n = 21, 38%), and pneumonia (n = 6, 11%).


Conclusion
Pom‐PAD‐Dara represents a promising multiagent regimen in heavily pretreated RRMM patients with high ORR and an acceptable safety profile.
KW  - multiple myeloma
KW  - Pom‐PAD‐Dara
KW  - refractory
KW  - relapse
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218029
VL  - 9
IS  - 16
ER  -