@article{ZhouFluechterNickeletal.2020, author = {Zhou, Xiang and Fl{\"u}chter, Patricia and Nickel, Katharina and Meckel, Katharina and Messerschmidt, Janin and B{\"o}ckle, David and Knorz, Sebastian and Steinhardt, Maximilian Johannes and Krummenast, Franziska and Danhof, Sophia and Einsele, Hermann and Kort{\"u}m, K. Martin and Rasche, Leo}, title = {Carfilzomib based treatment strategies in the management of relapsed/refractory multiple myeloma with extramedullary disease}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers12041035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203704}, year = {2020}, abstract = {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.}, language = {en} } @article{SteinhardtKrummenastRosenwaldetal.2022, author = {Steinhardt, Maximilian J. and Krummenast, Franziska C. and Rosenwald, Andreas and Gerhard-Hartmann, Elena and Heidemeier, Anke and Einsele, Hermann and Topp, Max S. and Duell, Johannes}, title = {R-CHOP intensification with mid-cycle methotrexate and consolidating AraC/TT with BCNU/aHSCT in primary aggressive lymphoma with CNS involvement}, series = {Journal of Cancer Research and Clinical Oncology}, volume = {148}, journal = {Journal of Cancer Research and Clinical Oncology}, number = {1}, issn = {1432-1335}, doi = {10.1007/s00432-021-03663-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267731}, pages = {205-214}, year = {2022}, abstract = {Purpose Patients suffering from aggressive systemic peripheral lymphoma with primary central nervous system involvement (PCL) are a rare and sparsely investigated population. Recommended treatment regimens include a combination of intrathecal and systemic chemotherapy as well as whole brain radiotherapy while offering relatively poor survival. Methods We conducted a single-center retrospective study that analyzed safety and outcome of 4 + 4 cycles Rituximab (R)-CHOP and R-high-dose Methotrexate (HD-MTX) for newly diagnosed, transplant-eligible patients ("Ping-Pong"), followed by Cytarabine (AraC)/Thiotepa (TT), BCNU/TT, and autologous hematologic stem cell transplantation (aHSCT). We retrospectively analyzed a set of 16 patients with high-intermediate or high-risk IPI status. Results Overall response rate to Ping-Pong was 100\% measured by CT/MRI, including 93.75\% complete remissions after BCNU/TT followed by PBSCT. One patient failed to qualify for high-dose chemotherapy due to progression when receiving Cytarabine/TT. All patients experienced grade III adverse events, 3 of them a grade IV adverse event. Estimated progression-free survival is 93.75\% after a 4.8-year follow-up currently. Conclusion Our study suggests high effectivity of R-CHOP with mid-cycle MTX with aHSCT consolidation towards acceptable OS results in this challenging patient population.}, language = {en} } @article{ZhouSteinhardtDuelletal.2020, author = {Zhou, Xiang and Steinhardt, Maximilian Johannes and D{\"u}ll, Johannes and Krummenast, Franziska and Danhof, Sophia and Meckel, Katharina and Nickel, Katharina and Grathwohl, Denise and Leicht, Hans-Benno and Rosenwald, Andreas and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Martin}, title = {Obinutuzumab and venetoclax induced complete remission in a patient with ibrutinib-resistant non-nodal leukemic mantle cell lymphoma}, series = {European Journal of Haematology}, volume = {104}, journal = {European Journal of Haematology}, number = {4}, doi = {10.1111/ejh.13382}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215513}, pages = {352 -- 355}, year = {2020}, abstract = {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.}, language = {en} } @article{ZhouSteinhardtGrathwohletal.2020, author = {Zhou, Xiang and Steinhardt, Maximilian J. and Grathwohl, Denise and Meckel, Katharina and Nickel, Katharina and Leicht, Hans-Benno and Krummenast, Franziska and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Klaus M.}, title = {Multiagent therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab ("Pom-PAD-Dara") in relapsed/refractory multiple myeloma}, series = {Cancer Medicine}, volume = {9}, journal = {Cancer Medicine}, number = {16}, doi = {10.1002/cam4.3209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218029}, pages = {5819-5826}, year = {2020}, abstract = {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.}, language = {en} } @article{SteinhardtZhouKrummenastetal.2020, author = {Steinhardt, Maximilian Johannes and Zhou, Xiang and Krummenast, Franziska and Meckel, Katharina and Nickel, Katharina and B{\"o}ckle, David and Messerschmidt, Janin and Knorz, Sebastian and Dierks, Alexander and Heidemeier, Anke and Lapa, Constantin and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Klaus Martin}, title = {Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma}, series = {International Journal of Immunopathology and Pharmacology}, volume = {34}, journal = {International Journal of Immunopathology and Pharmacology}, doi = {10.1177/2058738420980258}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236235}, pages = {1-5}, year = {2020}, abstract = {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.}, language = {en} }