16 results on '"Baertsch, Marc‐Andrea"'
Search Results
2. T cell-mediated curation and restructuring of tumor tissue coordinates an effective immune response
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Hickey, John W., Haist, Maximillian, Horowitz, Nina, Caraccio, Chiara, Tan, Yuqi, Rech, Andrew J., Baertsch, Marc-Andrea, Rovira-Clavé, Xavier, Zhu, Bokai, Vazquez, Gustavo, Barlow, Graham, Agmon, Eran, Goltsev, Yury, Sunwoo, John B., Covert, Markus, and Nolan, Garry P.
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- 2023
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3. Bortezomib-based induction therapy with high or low-dose dexamethasone in newly diagnosed, transplant-eligible multiple myeloma
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Mai, Elias K., Hielscher, Thomas, Bertsch, Uta, Schlenzka, Jana, Salwender, Hans J., Munder, Markus, Gerecke, Christian, Dührsen, Ulrich, Brossart, Peter, Neben, Kai, Hillengass, Jens, Raab, Marc S., Merz, Maximilian, Baertsch, Marc-Andrea, Jauch, Anna, Hose, Dirk, Martin, Hans, Lindemann, Hans-Walter, Blau, Igor W., Scheid, Christof, Weisel, Katja C., Goldschmidt, Hartmut, and for the German-speaking Myeloma Multicenter Group (GMMG)
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- 2019
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4. Comparison of biosimilar filgrastim, originator filgrastim, and lenograstim for autologous stem cell mobilization in patients with multiple myeloma
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Lisenko, Katharina, Baertsch, Marc‐Andrea, Meiser, Renate, Pavel, Petra, Bruckner, Thomas, Kriegsmann, Mark, Schmitt, Anita, Witzens‐Harig, Mathias, Ho, Anthony D., Hillengass, Jens, and Wuchter, Patrick
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- 2017
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5. Convenient Access to Expert-Reviewed Health Information via an Alexa Voice Assistant Skill for Patients With Multiple Myeloma: Development Study.
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Baertsch, Marc-Andrea, Decker, Sarah, Probst, Leona, Joneleit, Stefan, Salwender, Hans, Frommann, Franziska, and Buettner, Hartwig
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- 2022
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6. Lenalidomide versus bortezomib maintenance after frontline autologous stem cell transplantation for multiple myeloma.
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Baertsch, Marc-Andrea, Mai, Elias K., Hielscher, Thomas, Bertsch, Uta, Salwender, Hans J., Munder, Markus, Fuhrmann, Stephan, Dührsen, Ulrich, Brossart, Peter, Neben, Kai, Schlenzka, Jana, Kunz, Christina, Raab, Marc S., Hillengaß, Jens, Jauch, Anna, Seckinger, Anja, Hose, Dirk, Luntz, Steffen, Sonneveld, Pieter, and Lokhorst, Henk
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BORTEZOMIB ,ANTINEOPLASTIC agents ,DRUG efficacy ,MULTIPLE myeloma treatment ,STEM cell transplantation ,CANCER chemotherapy ,CLINICAL trials - Abstract
Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m
2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with- Published
- 2021
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7. Therapeutic monoclonal antibodies in combination with pomalidomide can overcome refractoriness to both agents in multiple myeloma: A case-based approach.
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Baertsch, Marc‐Andrea, Hundemer, Michael, Hillengass, Jens, Goldschmidt, Hartmut, Raab, Marc S., and Baertsch, Marc-Andrea
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MONOCLONAL antibodies ,MULTIPLE myeloma ,NEOVASCULARIZATION inhibitors ,SURVIVAL analysis (Biometry) ,PHARMACODYNAMICS ,THALIDOMIDE ,THERAPEUTICS - Abstract
In multiple myeloma (MM), the synergy between immunomodulatory drugs (IMiDs) and monoclonal antibodies (MABs) has been demonstrated in several pivotal trials. However, disease refractory to either class of compounds remains a major therapeutic challenge. We here report on 3 heavily pretreated MM patients who were refractory to pomalidomide as well as to MABs against CD38 (daratumumab) or CD20 (rituximab), respectively, but who responded to retreatment with the same agents in combination. Responses were durable with PFS of 7, 10 (ongoing), and 30 months from initiation of combination treatment. The combination of IMiDs with MABs directed against MM cell surface antigens can overcome refractoriness to both agents. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Efficacy and tolerability of the histone deacetylase inhibitor panobinostat in clinical practice.
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Baertsch, Marc‐Andrea, Hillengass, Jens, Blocka, Joanna, Schönland, Stefan, Hegenbart, Ute, Goldschmidt, Hartmut, Raab, Marc S., and Baertsch, Marc-Andrea
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ENZYME inhibitors ,HYDROXY acids ,INDOLE compounds ,PHARMACODYNAMICS ,THERAPEUTICS - Abstract
The histone deacetylase inhibitor panobinostat has shown efficacy in phase-II and phase-III trials for multiple myeloma and has recently received market approval in combination with bortezomib and dexamethasone. Here, we retrospectively report our single center experience with panobinostat/bortezomib/dexamethasone (FVD) in a heavily pretreated patient population (n = 24) with a high degree of refractoriness to proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Median age was 67 years (range 49-87) and the median number of prior therapies was 5 (range 2-17). Fourteen patients (58%) had high-risk cytogenetic aberrations. Thirteen (54%) and 21 (88%) patients were refractory to PIs and IMiDs, respectively. Twelve patients (50%) were refractory to bortezomib and 7 (29%) to carfilzomib; 6 patients (25%) were refractory to both bortezomib and carfilzomib. In 21 patients evaluable for response, overall response rate (ORR; ≥PR) was 33% (7/21) and 81% (17/21) achieved at least stable disease. Median progression-free survival (PFS) and overall survival were 3.5 and 9.8 months, respectively. Significant differences between bortezomib-sensitive and -refractory patients were observed. In bortezomib-sensitive patients, median PFS was 6.3 months compared to 2.3 months in bortezomib-refractory patients (P < .001). Median overall survival was not reached vs 4.8 months (P = .046) in bortezomib-sensitive and bortezomib-refractory patients, respectively. The only patient refractory to carfilzomib but sensitive to bortezomib achieved very good partial remission and PFS of 6.3 months, suggesting discrete mechanisms of resistance to different PIs. As expected, thrombocytopenia and fatigue/asthenia occurred in nearly all patients (96% and 83%, respectively). Diarrhea was observed in only 19% of patients which compares favorably with the high rates of diarrhea reported in the PANORAMA trials. With panobinostat dose reductions in 67% of patients, FVD was tolerated by the majority of patients. In conclusion, FVD showed efficacy in a heavily pretreated, high-risk multiple myeloma population with a high degree of patients refractory to novel agents including PIs. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Platelet Count before Peripheral Blood Stem Cell Mobilization Is Associated with the Need for Plerixafor But Not with the Collection Result.
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Baertsch, Marc-Andrea, Kriegsmann, Katharina, Pavel, Petra, Bruckner, Thomas, Hundemer, Michael, Kriegsmann, Mark, Ho, Anthony D., Goldschmidt, Hartmut, and Wuchter, Patrick
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BLOOD platelets , *BLOOD transfusion , *LEUCOCYTES , *BLOOD cell count , *BONE marrow - Abstract
Background: A low platelet count before mobilization has recurrently been identified as risk factor for poor mobilization. Methods: To determine the relevance of this finding for peripheral blood stem cell (PBSC) mobilization, including pre-emptive or rescue plerixafor in the case of poor mobilization, we retrospectively analyzed all patients undergoing PBSC collection at our institution between January 2014 and December 2015 (n = 380). Results: In total, 99% of the patients (377/380) successfully collected a minimum of 2 × 106 CD34+ cells/kg body weight sufficient for a single transplant. Rescue or pre-emptive plerixafor was administered to 11% of the patients (42/380). No correlations between the platelet count before mobilization and the number of peripheral blood CD34+ cells or the CD34+ cell collection result were detected in the entire population or the subgroups according to diagnosis (newly diagnosed multiple myeloma, relapsed multiple myeloma, lymphoma, amyloid light-chain amyloidosis, sarcoma, or germ cell tumor). However, patients requiring pre-emptive or rescue plerixafor had a significantly lower platelet count before mobilization (217/nl vs. 245/nl; p = 0.004). Conclusion: With the current state of the art PBSC mobilization strategies, the platelet count before mobilization was not associated with the CD34+ cell collection result but was associated with the need for pre-emptive or rescue application of plerixafor. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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10. Cyclophosphamide-based stem cell mobilization in relapsed multiple myeloma patients: A subgroup analysis from the phase III trial Re LApsE.
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Baertsch, Marc‐Andrea, Schlenzka, Jana, Lisenko, Katharina, Krzykalla, Julia, Becker, Natalia, Weisel, Katja, Noppeney, Richard, Martin, Hans, Lindemann, Hans W., Haenel, Mathias, Nogai, Axel, Scheid, Christof, Salwender, Hans, Fenk, Roland, Graeven, Ullrich, Reimer, Peter, Schmidt‐Hieber, Martin, Goerner, Martin, Schmidt‐Wolf, Ingo G. H., and Klein, Stefan
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MULTIPLE myeloma treatment , *STEM cells , *CYCLOPHOSPHAMIDE , *CANCER relapse , *BONE marrow transplantation , *CLINICAL trials - Abstract
Objective Analysis of the efficiency and toxicity of cyclophosphamide-based stem cell mobilization in patients with relapsed multiple myeloma ( RMM). Methods Peripheral blood stem cells ( PBSCs) were mobilized with high dose cyclophosphamide (2 g/m2 daily on days 1 and 2) and G- CSF plus pre-emptive/rescue plerixafor in RMM patients (first to third relapse) treated within the Re LApsE trial of the German-Speaking Myeloma Multicenter Group ( GMMG). Results Mobilization was initiated with high-dose cyclophosphamide (HD-CY) and G- CSF in 30 patients. Fifteen patients received additional pre-emptive/rescue administration of plerixafor. Stem cell collection was successful (≥2×106 CD34+ cells per kg bw) in 77% (23/30 patients). Patients with prior high-dose melphalan collected a significantly lower median total number of PBSCs than patients without prior high-dose melphalan (3.3×106 vs 17×106 CD34+ cells/kg bw). Toxicity of HD-CY was frequent with 12 serious adverse events ( SAE) in 37% of patients (11/30 patients). Infections accounted for the majority of SAE reports. In two patients, SAEs were lethal (septic shock). Conclusions These data proof feasibility of PBSC collection at relapse but emphasize the importance of collection and storage of additional PBSC transplants during first-line treatment when mobilization is more efficient and less toxic. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Evaluation of Stem Cell Mobilization in Patients with Multiple Myeloma after Lenalidomide-Based Induction Chemotherapy within the GMMG-HD6 Trial
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Wuchter, Patrick, Bertsch, Uta, Salwender, Hans-Juergen, Munder, Markus, Haenel, Mathias, Benner, Axel, Becker, Natalia, Fenk, Roland, Duerig, Jan, Blau, Igor Wolfgang, Lisenko, Katharina, Hillengass, Jens, Raab, Marc S., Baertsch, Marc Andrea, Seidel-Glaetzer, Andrea, Ho, Anthony D, Graeven, Ullrich, Scheid, Christof, Weisel, Katja, and Goldschmidt, Hartmut
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- 2016
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12. Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.
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Baertsch, Marc-Andrea, Schlenzka, Jana, Mai, Elias K., Merz, Maximilian, Hillengaß, Jens, Raab, Marc S., Hose, Dirk, Wuchter, Patrick, Ho, Anthony D., Jauch, Anna, Hielscher, Thomas, Kunz, Christina, Luntz, Steffen, Klein, Stefan, Schmidt-Wolf, Ingo G. H., Goerner, Martin, Schmidt-Hieber, Martin, Reimer, Peter, Graeven, Ullrich, and Fenk, Roland
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MULTIPLE myeloma treatment , *DEXAMETHASONE , *STEM cell transplantation , *DISEASE relapse , *PROGRESSION-free survival , *CANCER chemotherapy - Abstract
Background: Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients.Methods/design: ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS.Discussion: This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients.Trial Registration: ISRCTN16345835 (date of registration 2010-08-24). [ABSTRACT FROM AUTHOR]- Published
- 2016
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13. Carfilzomib, Lenalidomide, and Dexamethasone Followed by Salvage Autologous Stem Cell Transplant with or without Maintenance for Relapsed or Refractory Multiple Myeloma.
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Baertsch, Marc-Andrea, Fougereau, Mathilde, Hielscher, Thomas, Sauer, Sandra, Breitkreutz, Iris, Jordan, Karin, Müller-Tidow, Carsten, Goldschmidt, Hartmut, Raab, Marc-Steffen, Hillengass, Jens, and Giesen, Nicola
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STEM cell transplantation , *THERAPEUTIC use of protease inhibitors , *DISEASE progression , *SURVIVAL , *THALIDOMIDE , *DEXAMETHASONE , *TIME , *CANCER relapse , *CANCER patients , *DESCRIPTIVE statistics , *MULTIPLE myeloma , *SALVAGE therapy - Abstract
Simple Summary: High-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) is a standard treatment in patients with newly diagnosed multiple myeloma (MM). At relapse, salvage HDCT/ASCT is a treatment option in patients with sufficient benefit from frontline HDCT/ASCT, but no evidence is currently available regarding its role in the era of triplet regimens combining the most active drug classes for relapsed MM. To evaluate the outcome after salvage HDCT/ASCT following re-induction treatment with carfilzomib/lenalidomide/dexamethasone (KRD) and to identify prognostic factors, we conducted a retrospective analysis of patients that had previously undergone frontline HDCT/ASCT. We found that deep remissions achieved with KRd followed by salvage autologous transplantation were associated with favorable PFS and were enhanced by maintenance treatment. Salvage autologous transplantation after state-of-the-art triplet re-induction was a safe and effective strategy for RRMM patients that may offer the chance to avoid refractoriness to multiple novel agents at the next relapse. Salvage high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) is a treatment option for relapsed and/or refractory multiple myeloma (RRMM). No data are available on salvage HDCT/ASCT following re-induction treatment with state-of-the-art triplet regimens. We retrospectively report on 44 patients receiving salvage HDCT/ASCT following re-induction with carfilzomib/lenalidomide/dexamethasone (KRd). All patients received frontline HDCT/ASCT with median time to progression (TTP1) of 2.9 (1.2–13.5) years, enabling paired comparison of frontline and salvage HDCT/ASCT. After re-induction and before salvage transplant, 25/44 patients (57%) attained ≥ very good partial response (VGPR), which increased to 34/44 (77%) at best response after salvage HDCT/ASCT. Median progression-free survival (PFS) was 23.3 months from salvage HDCT/ASCT. Patients with ≥ VGPR at the time of salvage HDCT/ASCT and those receiving maintenance treatment post salvage HDCT/ASCT had significantly superior PFS (hazard ratio (HR) 0.19, p = 0.001 and HR 0.20, p = 0.009). In patients achieving at least an equal depth of response before salvage HDCT/ASCT as before frontline HDCT/ASCT, PFS after salvage HDCT/ASCT was comparable to the frontline situation (p = 0.3). This is the first report of state-of-the-art triplet re-induction and salvage HDCT/ASCT for RRMM after frontline transplantation. Deep remissions achieved with KRd translate into prolonged PFS following salvage HDCT/ASCT and are enhanced by maintenance treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE.
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Goldschmidt H, Baertsch MA, Schlenzka J, Becker N, Habermehl C, Hielscher T, Raab MS, Hillengass J, Sauer S, Müller-Tidow C, Luntz S, Jauch A, Hose D, Seckinger A, Brossart P, Goerner M, Klein S, Schmidt-Hieber M, Reimer P, Graeven U, Fenk R, Haenel M, Martin H, Lindemann HW, Scheid C, Nogai A, Salwender H, Noppeney R, Besemer B, and Weisel K
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- Adolescent, Adult, Aged, Animals, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Biopsy, Bone Marrow pathology, Chromosome Aberrations, Combined Modality Therapy, Female, Humans, Kaplan-Meier Estimate, Male, Mice, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Neoplasm Staging, Prognosis, Proportional Hazards Models, Salvage Therapy, Transplantation, Autologous, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy
- Abstract
The role of salvage high-dose chemotherapy and autologous stem cell transplantation (sHDCT/ASCT) for relapsed and/or refractory multiple myeloma (RRMM) in the era of continuous novel agent treatment has not been defined. This randomized, open-label, phase III, multicenter trial randomized patients with 1st-3rd relapse of multiple myeloma (MM) to a transplant arm (n = 139) consisting of 3 Rd (lenalidomide 25 mg, day 1-21; dexamethasone 40 mg, day 1, 8, 15, and 22; 4-week cycles) reinduction cycles, sHDCT (melphalan 200 mg/m
2 ), ASCT, and lenalidomide maintenance (10 mg/day) or to a control arm (n = 138) of continuous Rd. Median PFS was 20.7 months in the transplant and 18.8 months in the control arm (HR 0.87; 95% CI 0.65-1.16; p = 0.34). Median OS was not reached in the transplant and 62.7 months in the control arm (HR 0.81; 95% CI 0.52-1.28; p = 0.37). Forty-one patients (29%) did not receive the assigned sHDCT/ASCT mainly due to early disease progression, adverse events, and withdrawal of consent. Multivariate landmark analyses from the time of sHDCT showed superior PFS and OS (p = 0.0087/0.0057) in patients who received sHDCT/ASCT. Incorporation of sHDCT/ASCT into relapse treatment with Rd was feasible in 71% of patients and did not significantly prolong PFS and OS on ITT analysis while patients who received sHDCT/ASCT may have benefitted.- Published
- 2021
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15. Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients.
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Kriegsmann K, Baertsch MA, Awwad MHS, Merz M, Hose D, Seckinger A, Jauch A, Becker N, Benner A, Raab MS, Hillengass J, Bertsch U, Dürig J, Salwender HJ, Hänel M, Fenk R, Munder M, Weisel K, Müller-Tidow C, Goldschmidt H, and Hundemer M
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Adult, Aged, Biomarkers, Tumor, Carrier Proteins metabolism, Cytogenetic Analysis, Female, Gene Expression, Humans, Immunophenotyping, Male, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma metabolism, Neoplasm Staging, Protein Binding, Ubiquitin-Protein Ligases, Carrier Proteins genetics, Multiple Myeloma diagnosis, Multiple Myeloma genetics, Polyploidy
- Abstract
Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.
- Published
- 2019
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16. Enhanced Control of Oncolytic Measles Virus Using MicroRNA Target Sites.
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Leber MF, Baertsch MA, Anker SC, Henkel L, Singh HM, Bossow S, Engeland CE, Barkley R, Hoyler B, Albert J, Springfeld C, Jäger D, von Kalle C, and Ungerechts G
- Abstract
Measles viruses derived from the live-attenuated Edmonton-B vaccine lineage are currently investigated as novel anti-cancer therapeutics. In this context, tumor specificity and oncolytic potency are key determinants of the therapeutic index. Here, we describe a systematic and comprehensive analysis of a recently developed post-entry targeting strategy based on the incorporation of microRNA target sites (miRTS) into the measles virus genome. We have established viruses with target sites for different microRNA species in the 3' untranslated regions of either the N , F , H , or L genes and generated viruses harboring microRNA target sites in multiple genes. We report critical importance of target-site positioning with proximal genomic positions effecting maximum vector control. No relevant additional effect of six versus three miRTS copies for the same microRNA species in terms of regulatory efficiency was observed. Moreover, we demonstrate that, depending on the microRNA species, viral mRNAs containing microRNA target sites are directly cleaved and/or translationally repressed in presence of cognate microRNAs. In conclusion, we report highly efficient control of measles virus replication with various miRTS positions for development of safe and efficient cancer virotherapy and provide insights into the mechanisms underlying microRNA-mediated vector control.
- Published
- 2018
- Full Text
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