TY - JOUR A1 - Zhou, Xiang A1 - Dierks, Alexander A1 - Kertels, Olivia A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Samnick, Samuel A1 - Buck, Andreas K. A1 - Knorz, Sebastian A1 - Böckle, David A1 - Scheller, Lukas A1 - Messerschmidt, Janin A1 - Barakat, Mohammad A1 - Kortüm, K. Martin A1 - Rasche, Leo A1 - Einsele, Hermann A1 - Lapa, Constantin T1 - 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features JF - Cancers N2 - This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM. KW - 18F-FDG PET/CT KW - 11C-Methionine PET/CT KW - 68Ga-Pentixafor PET/CT KW - smoldering myeloma Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211240 SN - 2072-6694 VL - 12 IS - 8 ER - TY - JOUR A1 - Sánchez-Maldonado, Jose Manuel A1 - Moñiz-Díez, Ana A1 - ter Horst, Rob A1 - Campa, Daniele A1 - Cabrera-Serrano, Antonio José A1 - Martínez-Bueno, Manuel A1 - Garrido-Collado, María del Pilar A1 - Hernández-Mohedo, Francisca A1 - Fernández-Puerta, Laura A1 - López-Nevot, Miguel Ángel A1 - Cunha, Cristina A1 - González-Sierra, Pedro Antonio A1 - Springer, Jan A1 - Lackner, Michaela A1 - Alcazar-Fuoli, Laura A1 - Fianchi, Luana A1 - Aguado, José María A1 - Pagano, Livio A1 - López-Fernández, Elisa A1 - Clavero, Esther A1 - Potenza, Leonardo A1 - Luppi, Mario A1 - Moratalla, Lucia A1 - Solano, Carlos A1 - Sampedro, Antonio A1 - Cuenca-Estrella, Manuel A1 - Lass-Flörl, Cornelia A1 - Canzian, Federico A1 - Loeffler, Juergen A1 - Li, Yang A1 - Einsele, Hermann A1 - Netea, Mihai G. A1 - Vázquez, Lourdes A1 - Carvalho, Agostinho A1 - Jurado, Manuel A1 - Sainz, Juan T1 - Polymorphisms within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis: a two-stage case control study in the context of the aspBIOmics consortium JF - Journal of Fungi N2 - Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4\(_{rs7526628T/T}\) genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4\(_{rs7526628T}\) allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2\(_{rs12137965G}\) allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2\(_{rs17013271T}\) allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2\(_{rs12137965G}\) allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2\(_{rs17013271T}\) allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk. KW - invasive aspergillosis KW - TNFSF4 KW - MAPKAPK2 KW - genetic susceptibility KW - B cells KW - monocytes KW - serum biomarkers KW - TSLP KW - TNFSF14 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220107 SN - 2309-608X VL - 7 IS - 1 ER - TY - JOUR A1 - Constantinescu, Catalin A1 - Pasca, Sergiu A1 - Zimta, Alina-Andreea A1 - Tat, Tiberiu A1 - Rus, Ioana A1 - Teodorescu, Patric A1 - Iluta, Sabina A1 - Tanase, Alina A1 - Colita, Anca A1 - Sigurjonsson, Olafur A1 - Einsele, Hermann A1 - Tomuleasa, Ciprian T1 - Overview of the side-effects of FDA- and/or EMA-approved targeted therapies for the treatment of hematological malignancies JF - Journal of Clinical Medicine N2 - In the last decade there has been tremendous effort in offering better therapeutic management strategies to patients with hematologic malignancies. These efforts have ranged from biological to clinical approaches and resulted in the rapid development of new approaches. The main “problem” that comes with the high influx of newly approved drugs, which not only influences hematologists that frequently work with these drugs but also affects other healthcare professionals that work with hematologists in patient management, including intensive care unit (ICU) physicians, is they have to keep up within their specialty and, in addition, with the side-effects that can occur when encountering hematology-specific therapies. Nonetheless, there are few people that have an in-depth understanding of a specialty outside theirs. Thus, this manuscript offers an overview of the most common side-effects caused by therapies used in hematology nowadays, or that are currently being investigated in clinical trials, with the purpose to serve as an aid to other specialties. Nevertheless, because of the high amount of information on this subject, each chapter will offer an overview of the side-effects of a drug class with each reference of the section being intended as further reading. KW - novel therapies KW - life-threatening side-effects KW - hematological malignancies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213020 SN - 2077-0383 VL - 9 IS - 9 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 - Gründahl, Marie A1 - Wacker, Beate A1 - Einsele, Hermann A1 - Heinz, Werner J. T1 - Invasive fungal diseases in patients with new diagnosed acute lymphoblastic leukaemia JF - Mycoses N2 - Background Patients with acute leukaemia have a high incidence of fungal infections. This has primarily been shown in acute myeloid leukaemia and is different for acute lymphoblastic leukaemia. Until now no benefit of mould active prophylaxis has been demonstrated in the latter population. Methods In this retrospective single‐centre study, we analysed the incidence, clinical relevance, and outcome of invasive fungal diseases (IFD) as well as the impact of antifungal prophylaxis for the first 100 days following the primary diagnosis of acute lymphoblastic leukaemia. Results In 58 patients a high rate of proven, probable, and possible fungal infections could be demonstrated with a 3.4%, 8.6%, and 17.2% likelihood, respectively. The incidence might be even higher, as nearly 40% of all patients had no prolonged neutropenia for more than 10 days, excluding those from the European Organization of Research and Treatment of cancer and the Mycoses Study Group criteria for probable invasive fungal disease. The diagnosed fungal diseases had an impact on the duration of hospitalisation, which was 13 days longer for patients with proven/probable IFD compared to patients with no signs of fungal infection. Use of antifungal prophylaxis did not significantly affect the risk of fungal infection. Conclusion Patients with acute lymphoblastic leukaemia are at high risk of acquiring an invasive fungal disease. Appropriate criteria to define fungal infections, especially in this population, and strategies to reduce the risk of infection, including antifungal prophylaxis, need to be further evaluated. KW - acute lymphoblastic leukaemia KW - fungal infection KW - galactomannan KW - incidence KW - mortality Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217844 VL - 63 IS - 10 SP - 1101 EP - 1106 ER - TY - JOUR A1 - Einsele, Hermann A1 - Borghaei, Hossein A1 - Orlowski, Robert Z. A1 - Subklewe, Marion A1 - Roboz, Gail J. A1 - Zugmaier, Gerhard A1 - Kufer, Peter A1 - Iskander, Karim A1 - Kantarjian, Hagop M. T1 - The BiTE (Bispecific T‐Cell Engager) Platform: Development and Future Potential of a Targeted Immuno‐Oncology Therapy Across Tumor Types JF - Cancer N2 - Immuno‐oncology therapies engage the immune system to treat cancer. BiTE (bispecific T‐cell engager) technology is a targeted immuno‐oncology platform that connects patients' own T cells to malignant cells. The modular nature of BiTE technology facilitates the generation of molecules against tumor‐specific antigens, allowing off‐the‐shelf immuno‐oncotherapy. Blinatumomab was the first approved canonical BiTE molecule and targets CD19 surface antigens on B cells, making blinatumomab largely independent of genetic alterations or intracellular escape mechanisms. Additional BiTE molecules in development target other hematologic malignancies (eg, multiple myeloma, acute myeloid leukemia, and B‐cell non‐Hodgkin lymphoma) and solid tumors (eg, prostate cancer, glioblastoma, gastric cancer, and small‐cell lung cancer). BiTE molecules with an extended half‐life relative to the canonical BiTE molecules are also being developed. Advances in immuno‐oncology made with BiTE technology could substantially improve the treatment of hematologic and solid tumors and offer enhanced activity in combination with other treatments. KW - B cell KW - blinatumomab KW - hematologic malignancies KW - T cell KW - tumor‐specific antigen Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215426 VL - 126 IS - 14 SP - 3192 EP - 3201 ER - TY - JOUR A1 - Zhou, Xiang A1 - Steinhardt, Maximilian Johannes A1 - Düll, Johannes A1 - Krummenast, Franziska A1 - Danhof, Sophia A1 - Meckel, Katharina A1 - Nickel, Katharina A1 - Grathwohl, Denise A1 - Leicht, Hans‐Benno A1 - Rosenwald, Andreas A1 - Einsele, Hermann A1 - Rasche, Leo A1 - Kortüm, Martin T1 - Obinutuzumab and venetoclax induced complete remission in a patient with ibrutinib‐resistant non‐nodal leukemic mantle cell lymphoma JF - European Journal of Haematology N2 - We herein report the case of a 73‐year‐old male patient who was diagnosed with leukemic non‐nodal MCL. This patient had received six cycles of bendamustine, which resulted in a transient remission, and a second‐line therapy with ibrutinib, which unfortunately failed to induce remission. We started a treatment with single‐agent obinutuzumab at a dose of 20 mg on day 1, 50 mg on day 2‐4, 330 mg on day 5, and 1000 mg on day 6. The laboratory analysis showed a rapid decrease of leukocyte count. Four weeks later, we repeated the treatment with obinutuzumab at a dose of 1000 mg q4w and started a therapy with venetoclax at a dose of 400 mg qd, which could be increased to 800 mg qd from the third cycle. This combination therapy was well tolerated. The patient achieved a complete remission (CR) after three cycles of obinutuzumab and venetoclax. To date, the patient has a progression‐free survival of 17 months under ongoing obinutuzumab maintenance q4w. This is the first report about obinutuzumab and venetoclax induced CR in rituximab‐intolerant patient with an ibrutinib‐resistant MCL. This case suggests that obinutuzumab‐ and venetoclax‐based combination therapy might be salvage therapy in patients with ibrutinib‐resistant MCL. KW - mantle cell lymphoma KW - obinutuzumab KW - venetoclax Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215513 VL - 104 IS - 4 SP - 352 EP - 355 ER - TY - JOUR A1 - Luber, Verena A1 - Lutz, Mathias A1 - Thiede, Christian A1 - Haferlach, Claudia A1 - Dürk, Heinz Albert A1 - Einsele, Hermann A1 - Grigoleit, Götz Ulrich A1 - Mielke, Stephan T1 - Donor-cell leukemia with novel genetic features 2 years after sex-mismatched T cell-depleted haploidentical stem cell transplantation JF - Annals of Hematology N2 - No abstract available. KW - donor-cell leukemia Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232596 SN - 0939-5555 VL - 99 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 -