26 results on '"David H. Vesole"'
Search Results
2. P870: EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN (BCMA)-DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES
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Salomon Manier, Alexander Lesokhin, Mohamad Mohty, Ruben Niesvizky, Christopher Maisel, Bertrand Arnulf, Sarah M. Larson, Asya Nina Varshavsky-Yanovsky, Xavier Leleu, Lionel Karlin, David H. Vesole, Nizar J Bahlis, Carlos Fernandez de Larrea, Noopur Raje, Eric Leip, Sharon T. Sullivan, Mohamed Elmeliegy, Andrea Viqueira, and Ajay Nooka
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. I-OPen: inferior outcomes of penta-refractory compared to penta-exposed multiple myeloma patients
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Sarvarinder K. Gill, Rashmi Unawane, Shuqi Wang, Jaeil Ahn, Adolfo Aleman, David S. Siegel, David H. Vesole, Harsh Parmar, Pooja Phull, and Noa Biran
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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4. Mass-Fix better predicts for PFS and OS than standard methods among multiple myeloma patients participating on the STAMINA trial (BMT CTN 0702 /07LT)
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Angela Dispenzieri, Amrita Krishnan, Bonnie Arendt, Beth Blackwell, Paul K. Wallace, Surendra Dasari, Dan T. Vogl, Yvonne Efebera, Mingwei Fei, Nancy Geller, Sergio Giralt, Theresa Hahn, Alan Howard, Mindy Kohlhagen, Heather Landau, Parameswaran Hari, Marcelo C. Pasquini, Muzaffar H. Qazilbash, Philip McCarthy, Nina Shah, David H. Vesole, Edward Stadtmauer, and David Murray
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses are associated with better progression free survival (PFS) and overall survival (OS). To test the hypothesis that Mass-Fix, a mass spectrometry-based means to detect monoclonal proteins, is superior to existing methodologies to predict for survival outcomes, samples from the STAMINA trial (NCT01109004), a trial comparing three transplant approaches, were employed. Samples from 575 patients from as many as three time points (post-induction [post-I; pre-maintenance [pre-M]; 1 year post enrollment [1YR]) were tested when available. Four response parameters were assessed: Mass-Fix, serum immunofixation, complete response, and measurable residual disease (MRD) by next generation flow cytometry. Of the four response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses. Although MRD drove Mass-Fix from the model for PFS at post-I and pre-M, 1YR Mass-Fix was independent of 1YR MRD. For OS, the only prognostic pre-I measure was Mass-Fix, and the only 1YR measures that were prognostic on multivariate analysis were 1YR MRD and 1YR Mass-Fix. SIFE and CR were not. Mass-Fix is a powerful means to track response.
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- 2022
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5. Interaction between age and gender on survival outcomes in extramedullary multiple myeloma over the past two decades
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Ayrton I Bangolo, Pierre Fwelo, Chinmay Trivedi, Sowmya Sagireddy, Hamed Aljanaahi, Auda Auda, Maryama Mohamed, Sonia Onyeka, Miriam Fisher, Jyoti Thapa, Erwin J Tabucanon, Lyuben Georgiev, Annetta Wishart, Shilpee Kumari, Conrad Erikson, Mary Bangura, Orent Paddy, Rashmi Madhukar, Eugenio L Gomez, Joshua Rathod, Mansi Naria, Basel Hajal, Mohammad Awadhalla, David Siegel, Harsh Parmar, Noa Biran, David H Vesole, Pooja Phull, and Simcha Weissman
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Oncology - Published
- 2023
6. Hospital facility characteristics and socioeconomic factors on outcomes and treatment in patients with multiple myeloma: National Cancer Database analysis
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Kimberley Doucette, Allison O. Taylor, Bryan Chan, Xiaoyang Ma, Jaeil Ahn, David H. Vesole, and Catherine Lai
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Hematology ,General Medicine - Published
- 2023
7. Initial Results of Dose Escalation of ISB 1342, a Novel CD3xCD38 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM)
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Sanjay R Mohan, Cristiana Costa Chase, Jesus G Berdeja, Lionel Karlin, Karim Belhadj, Aurore Perrot, Philippe Moreau, Cyrille Touzeau, Thomas Chalopin, Alexander M Lesokhin, Carol Ann Huff, David H. Vesole, Joshua Richter, Jeffrey V. Matous, Igor Proscurshim, Eileen Wolff, Girish Gudi, Andrew Garton, Vinu Menon, Sunitha Gn, Yacine Salhi, Eric J. Feldman, and Mohamad Mohty
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
8. Impact of bortezomib‐based versus lenalidomide maintenance therapy on outcomes of patients with high‐risk multiple myeloma
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Naresh Bumma, Binod Dhakal, Raphael Fraser, Noel Estrada‐Merly, Kenneth Anderson, César O. Freytes, Gerhard C. Hildebrandt, Leona Holmberg, Maxwell M. Krem, Cindy Lee, Lazaros Lekakis, Hillard M. Lazarus, Hira Mian, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Ricardo Parrondo, Sagar S. Patel, Melhem Solh, Christopher Strouse, David H. Vesole, Shaji Kumar, Muzaffar H. Qazilbash, Nina Shah, Anita D’Souza, and Surbhi Sidana
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Cancer Research ,Oncology - Published
- 2023
9. Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis
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Brittany Knick Ragon, Mithun Vinod Shah, Anita D'Souza, Noel Estrada-Merly, Lohith Gowda, Gemlyn George, marcos DeLima, Shahrukh Hashmi, Mohamed A Kharfan-Dabaja, Navneet S Majhail, Rahul Banerjee, Ayman Saad, Gerhard C. Hildebrandt, Hira Mian, Muhammad Bilal Abid, Minoo Battiwalla, Lazaros J. Lekakis, Sagar S. Patel, Hemant S. Murthy, Yago Nieto, Christopher S Strouse, Sherif M. Badawy, Samer AI Al Hadidi, Bhagirathbhai Dholaria, Mahmoud Aljurf, David H Vesole, Cindy H Lee, Attaphol Pawarode, Usama Gergis, Kevin Charles Miller, Leona A Holmberg, Aimaz Afrough, Melhem M Solh, Pashna Munshi, Taiga Nishihori, Larry D. Anderson, Baldeep Wirk, Gurbakhash Kaur, Muzaffar H Qazilbash, Nina Shah, Shaji K Kumar, and Saad Z. Usmani
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Hematology - Abstract
The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials employing auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62, P
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- 2023
10. Monoclonal gammopathy of ocular significance (MGOS) – a short survey of corneal manifestations and treatment outcomes
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Markus Munder, Walter Lisch, Alessandro Gozzetti, Camila Peña, Kitti Kormányos, Joanna Wasielica-Poslednik, Mohammad Al Hariri, Laura Rosiñol, Nóra Szentmáry, Mateusz Krzystanski, Xiang Zhou, Anna Waszczuk-Gajda, David H. Vesole, Gabor Mikala, Artur Jurczyszyn, and Laurent Garderet
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Smoldering Multiple Myeloma ,Cancer Research ,medicine.medical_specialty ,Visual acuity ,genetic structures ,Monoclonal gammopathy of clinical significance ,monoclonal gammopathy of ocular significance ,Treatment outcome ,Paraproteinemias ,Plasma cell ,Monoclonal Gammopathy of Undetermined Significance ,Transplantation, Autologous ,Systemic therapy ,Gastroenterology ,multiple myeloma ,paraproteinemic keratopathy ,Corneal Diseases ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Clinical significance ,Multiple myeloma ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,eye diseases ,Monoclonal gammopathy ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Neoplasm Recurrence, Local ,medicine.symptom ,Multiple Myeloma ,business - Abstract
Monoclonal gammopathy of ocular significance (MGOS) is a rare subset of monoclonal gammopathy of clinical significance occurring secondary to plasma cell disorders and causing ocular manifestations. We identified 23 patients with paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of unknown significance (MGUS, 10), smoldering multiple myeloma (SMM, 3) or multiple myeloma (MM, 10). Many of these patients with PPK (11/23) presented decreased vision. All patients with MM and 40% of those with other diagnoses such as SMM and MGUS received systemic therapy with or without autologous stem cell transplantation. Four eyes of four patients were treated by penetrating keratoplasty. In most cases, neither ocular nor hematologic treatment afforded a durable improvement in the visual acuity (recurrence after a median of 11 months), despite initial responses. Further studies will be required to determine the optimal strategy to treat and prevent the relapse of ocular symptoms in patients with PPK.
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- 2021
11. Effect of a 6-Week Cycle of Nordic Walking Training on Vitamin 25(OH)D3, Calcium-Phosphate Metabolism and Muscle Damage in Multiple Myeloma Patients–Randomized Controlled Trial
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Olga Czerwińska-Ledwig, David H. Vesole, Anna Piotrowska, Joanna Gradek, Wanda Pilch, and Artur Jurczyszyn
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multiple myeloma ,physical activity ,vitamin D ,muscle damage ,calcium-phosphate metabolism ,General Medicine - Abstract
Introduction: Multiple myeloma (MM) is a hematological malignancy affecting older adults. One of the most common myeloma-defining events is the development of symptomatic lytic bone disease. The serum concentrations of calcium (Ca), inorganic phosphorus (P), and vitamin 25(OH)D3 in the serum reflect bone metabolism. An enzyme lactate dehydrogenase (LDH) is a marker of muscle damage, but its serum activity also has an important prognostic value in MM. Myoglobin (Mb) is a small protein present in muscles; its serum level increases when myocytes are damaged. Objectives: In this study, the impact of a 6-week Nordic walking (NW) exercise program on blood parameters related to calcium-phosphate metabolism and damage of skeletal muscles was assessed. Patients and methods: A total of 33 patients with MM in the remission stage, without cytostatic treatment, were allocated and randomly assigned to one of two groups: 17 in the training group (NW) and 16 in the control group (CG). All patients were supplemented per os with vitamin D3 and calcium carbonate daily and received zoledronic acid every 4 weeks (intravenous). Nordic walking training sessions took place 3 times a week for 6 weeks, 1 h each. Blood samples were drawn before and after the 6 weeks of training sessions to assess the serum concentrations of vitamin 25(OH)D3, P, Ca, Mb, and LDH. Results: Patients from the NW group showed a statistically significant decrease in mean serum myoglobin concentration (p = 0.018) and an increase in 25(OH)D3 (p < 0.001) and total Ca (p = 0.001) concentrations. There were no statistically significant changes in the results obtained in CG. Between groups, after 6 weeks, Mb serum concentration was significantly lower in NW (p = 0.041), and 25(OH)D3 was higher (p < 0.001) compared to CG. There was a correlation between the changes in myoglobin, phosphorus, 25(OH)D3, and Ca concentrations after 6 weeks. Conclusions: NW training is a safe and beneficial form of physical exercise for patients with MM without inducing muscle damage. NW performed outside improves serum vitamin 25(OH)D3 concentration.
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- 2022
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12. Use of eculizumab in autologous hematopoietic stem cell transplantation-associated thrombotic microangiopathy in two adults
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Aquino Williams, Koen van Besien, David H. Vesole, Mohammad Alhomoud, Cynthia M. Magro, and Jeffrey Laurence
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Hemolytic anemia ,Cancer Research ,Thrombotic microangiopathy ,business.industry ,medicine.medical_treatment ,Hematology ,Hematopoietic stem cell transplantation ,Eculizumab ,medicine.disease ,Oncology ,hemic and lymphatic diseases ,Immunology ,medicine ,Thrombotic Microangiopathies ,business ,medicine.drug - Abstract
Transplant-associated thrombotic microangiopathies (TA-TMAs) are inflammatory and thrombotic disorders of the microvasculature characterized by hemolytic anemia, thrombocytopenia, and organ dysfunc...
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- 2021
13. Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost
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Ayrton Bangolo, Samir Oza, Ronit Slotky, Aimee Chappell, David Siegel, Harsh Parmar, Noa Biran, David H. Vesole, and Pooja Phull
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
14. The Clinical Characteristics and Epidemiology of Extramedullary Multiple Myeloma over the Past Two Decades
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Ayrton Bangolo, Pierre Fwelo, Chinmay Trivedi, Jennifer Hashem, Parul Jandir, Katamon Klaichart, Rua Abdelrahim, Ayodya R Perera, Manbir Singh, Rohini B Gurumoorthy, Apurva Tiwari, Sudha S Konakanchi, Nagihan Orhun, Adithya Polavarapu, Ritika Sharma, Ankit Sarkar, Anupama Gupta, Bob-Hallen E. Treisma, Thin Thiri Soe, Ashwin Penchala, Sheetal Penmetsa, Srikar Bathi, Padmavathi Muppalla, David Siegel, Noa Biran, Harsh Parmar, David H. Vesole, Simcha Weissman, and Pooja Phull
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
15. Effect of Daratumumab on Stem Cell Mobilization and Engraftment Kinetics Post Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma
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Samir Oza, Ronit Slotky, Pranay Vissa, Pooja Phull, Sukhdeep Kaur, Hyung C. Suh, Michele L. Donato, Scott D. Rowley, Noa Biran, David H. Vesole, David Siegel, and Harsh Parmar
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
16. Recent Advancements and Future Directions in Frontline Treatment of Multiple Myeloma
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Kimberley R, Doucette and David H, Vesole
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Antineoplastic Combined Chemotherapy Protocols ,Humans ,Multiple Myeloma ,Lenalidomide - Published
- 2022
17. The Current State of Knowledge About Evolution of Multiple Myeloma to Plasma Cell Leukemia
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Artur Jurczyszyn, Magdalena Olszewska-Szopa, and David H. Vesole
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Cancer Research ,Oncology ,Hematology - Abstract
Plasma cell leukemia is a rare form of multiple myeloma (MM). In contrast to de novo primary plasma cell leukemia (pPCL), which is very uncommon presentation of MM, there is increasing frequency of transformation to secondary plasma cell leukemia (sPCL) with increasing survival of patients (MM). The molecular basis of sPCL remains poorly understood sPCL is particularly aggressive and is associated with an extremely poor prognosis, constituting a major unmet medical need. High-quality data in sPCL regarding presentation, treatment and outcomes is limited. Herein we review the current state of knowledge on sPCL diagnostics, molecular biology, clinical characteristics, prognosis and reported treatment outcomes and the emergence of the new therapeutic strategies.
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- 2022
18. A Multicenter Phase II, Double-Blind, Placebo-Controlled Trial of Maintenance Ixazomib After Allogeneic Transplantation for High-Risk Multiple Myeloma: Results of the Blood and Marrow Transplant Clinical Trials Network 1302 Trial
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Qaiser Bashir, Taiga Nishihori, Marcelo C. Pasquini, Michael J. Martens, Juan Wu, Melissa Alsina, Claudio Anasetti, Claudio Brunstein, Peter Dawson, Yvonne Efebera, Cristina Gasparetto, Nancy Geller, Sergio Giralt, Aric C. Hall, John Koreth, Philip McCarthy, Emma Scott, Edward A. Stadtmauer, David H. Vesole, and Parameswaran Hari
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
The role of allogeneic hematopoietic cell transplantation (allo-HCT) followed by maintenance therapy in high-risk multiple myeloma (MM) remains controversial. We evaluated the efficacy of ixazomib maintenance therapy after reduced-intensity conditioning allo-HCT from HLA-matched donors in patients with high-risk MM. The primary study endpoint was progression-free survival (PFS) postrandomization, treated as a time to event. Secondary endpoints were grade II-IV and grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, best response, disease progression, nonrelapse mortality (NRM), overall survival (OS), toxicity, infection, and health-related quality of life. In this phase 2, double-blinded, prospective multicenter trial, we randomized patients with high-risk MM (ie, those with poor-risk cytogenetics, plasma cell leukemia, or relapsing within 24 months after autologous HCT) to ixazomib (3 mg on days 1, 8, and 15) or placebo after allo-HCT. The conditioning regimen included fludarabine/melphalan/bortezomib with tacrolimus plus methotrexate for GVHD. Fifty-seven patients were enrolled, of whom 52 (91.2%) underwent allo-HCT and 43 (82.7%) were randomized to ixazomib versus placebo. At 21 months postrandomization, the ixazomib and placebo groups had similar PFS (55.3% versus 59.1%; P = 1.00) and OS (94.7% versus 86.4%; P = .17). The cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% versus 0%) and chronic GVHD at 12 months (68.6% versus 63.6%) also were similar in the 2 groups. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OS were 52% and 82%, respectively, with a corresponding NRM of 11.7%. These results demonstrate the safety and durable disease control with allo-HCT in high-risk MM patients. We could not adequately assess the efficacy of ixazomib maintenance because the trial terminated early owing to enrollment delays, but there was no indication of any impact on outcomes.
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- 2022
19. Effect of a 6-week Cycle of Nordic Walking Training on Vitamin 25(OH)D3 Calcium-phosphate Metabolism and Muscle Damage in Multiple Myeloma Patients
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Olga Czerwińska-Ledwig, David H Vesole, Wanda Pilch, Joanna Gradek, and Artur Jurczyszyn
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Introduction: Multiple myeloma (MM) is a hematological malignancy affecting older adults (median age 70 years). One of the most common myeloma defining events is the development of symptomatic lytic bone disease which leads to fractures and immobilization. It is caused by disturbances in bone metabolism affecting calcium-phosphate balance. Treatment of the bone disease and the underlying malignancy results in disease and symptom control.Objectives: In this study, the impact of a 6-week Nordic walking (NW) exercise program on blood parameters related to calcium-phosphate metabolism and damage of skeletal muscles was assessed. Patients and methods: 28 subjects with MM in remission stage, without cytostatic treatment were enrolled and completed the study: 15 in the training group (NW) and 13 in control group (CG). All patients were supplemented with vitamin D3, calcium carbonate daily and received zoledronic acid every 4 weeks. Two venous blood samples were drawn – before and after the 6 weeks of training sessions – to assess the serum concentrations of vitamin 25(OH)D3, inorganic phosphorus, total calcium, myoglobin, and lactate dehydrogenase (LDH).Results: Patients from the NW group showed a statistically significant decrease in mean serum myoglobin concentration (p=0.018) and increase in 25(OH)D3 (p3 and Ca concentrations after 6 weeks.Conclusions: NW training is a safe and beneficial form of physical exercise for patients with MM without inducing muscle damage. NW performed outside during Spring-Summer season improves serum vitamin 25(OH)D3 concentration.
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- 2022
20. Venetoclax in upfront induction therapy for primary plasma cell leukemia with t(11;14) or BCL2 expression
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Tina Roy, Joseph B. An, Kimberly Doucette, Aimee M. Chappell, and David H. Vesole
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Cancer Research ,Sulfonamides ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,Humans ,Antineoplastic Agents ,Hematology ,Induction Chemotherapy ,Bridged Bicyclo Compounds, Heterocyclic ,Leukemia, Plasma Cell - Published
- 2022
21. POEMS syndrome : real world experience in diagnosis and systemic therapy - 108 patients multicenter analysis
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Kari Flicker, Alessandro Gozzetti, Shuhua Yi, Santiago Thibaud, Rebecca Silbermann, Ravi Vij, Iwona Hus, Katarzyna Krzanowska, Julio Davila Valls, Artur Jurczyszyn, Aimee Chappell, Magdalena Olszewska-Szopa, Edvan de Queiroz Crusoe, Aleksander Salomon-Perzyński, Carmen Montes Gaisan, Santosh Kumar Chellapuram, David H. Vesole, Lalit Kumar, Jacek Czepiel, Fang Xu, Joshua Richter, Anna Suska, Mark A. Fiala, Enrique M. Ocio, Jorge J. Castillo, Anna Waszczuk-Gajda, and Universidad de Cantabria
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Cancer Research ,Pediatrics ,medicine.medical_specialty ,Multivariate analysis ,Anemia ,Paraproteinemias ,plasma cell dyscrsia, POEMS, standard of care ,Disease ,Transplantation, Autologous ,Systemic therapy ,Organomegaly ,Plasma cell dyscrsia ,medicine ,Humans ,Standard of care ,POEMS ,Retrospective Studies ,POEMS syndrome ,business.industry ,Bortezomib ,Hematology ,plasma cell dyscrsia ,medicine.disease ,Oncology ,standard of care ,POEMS Syndrome ,medicine.symptom ,business ,Proteasome Inhibitors ,Polyneuropathy ,medicine.drug - Abstract
POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.
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- 2022
22. Supportive care in multiple myeloma
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Artur Jurczyszyn, Grzegorz Charliński, and David H. Vesole
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Oncology ,Hematology - Published
- 2022
23. TTI-622-01: A phase 1a/1b dose-escalation and expansion trial of TTI-622 in patients with advanced hematologic malignancies, including multiple myeloma
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Krish Patel, Robert Z. Orlowski, Kimberley Doucette, Michael Maris, Matthew James Pianko, Radhakrishnan Ramchandren, Don A. Stevens, David H. Vesole, Robert A. Uger, Anita Scheuber, Naomi Molloy, Ingmar Bruns, and Alexander M. Lesokhin
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Cancer Research ,Oncology - Abstract
TPS8071 Background: CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a "don’t eat me" signal to suppress macrophage phagocytosis. TTI-622 is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4. It is designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro-phagocytic signal via IgG4 Fc. CD47 is significantly increased in multiple myeloma (MM) bone marrow mononuclear cells and expression inversely correlates with survival in patients. Relapsed/Refractory (R/R) MM shows particularly high expression of CD47. Preclinical studies demonstrate that the addition of proteasome inhibitors to CD47 blockade significantly increases phagocytosis of MM cells in vitro and anti-myeloma activity in vivo. The ongoing phase 1a part of this study has been previously described. The phase 1b part of the study will determine the safety and efficacy of TTI-622 when given as monotherapy or in combination with selected approved anticancer treatments in patients with hematological malignancies where new treatments with novel mechanism of action are needed. Here we describe 5 RRMM cohorts within phase 1b of the study. Methods: TTI-622-01 is a multi-center Phase 1a/1b study. Phase 1a was designed to determine the MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of QW, Q2W, and Q3W single-agent TTI-622 in R/R lymphoma using a 3+3 dose escalation schema. Phase 1b, ongoing, will determine the safety and recommended dose of TTI-622 to be given as single agent and in combination with carfilzomib + dexamethasone (Kd) in RRMM and will evaluate the preliminary efficacy. Secondary objectives are to further characterize the safety, PK and immunogenicity of TTI-622 when combined with Kd. Patients will be enrolled in 5 separate cohorts: 3 cohorts will explore different doses and administration schedules of TTI-622 combined with the approved dose of Kd; 2 cohorts will explore different doses of TTI-622 monotherapy. Cohorts will be opened in a staggered manner. In each cohort 3 patients will be dosed and followed for 28 days (21 days in the monotherapy) before expanding enrolment to approximately an additional 27 patients. Key eligibility criteria include: relapse or progression following ≥3 prior lines of therapy (including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody), carfilzomib-refractory progressive and measurable disease per IMWG at study entry; age ≥18 years; ECOG performance status ≤2; adequate organ functions; no known CNS involvement; no prior anti-CD47 or anti-SIRPα therapy. Patient recruitment is planned or ongoing at 40 sites worldwide. Clinical trial information: NCT03530683.
- Published
- 2022
24. Monoclonal Gammopathy of Ocular Significance (MGOS) - a Series of Corneal Manifestations and Treatment Outcomes
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Kitti Kormányos, Camila Peña, Joanna Wasielica-Poslednik, Alessandro Gozzetti, Nóra Szentmáry, Gabor Mikala, Xiang Zhou, Artur Jurczyszyn, Laurent Garderet, Mohammad Al Hariri, Markus Munder, Mateusz Krzystanski, David H. Vesole, Laura Rosiñol, Anna Waszczuk-Gajda, and Walter Lisch
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medicine.medical_specialty ,Monoclonal gammopathy ,business.industry ,Immunology ,Treatment outcome ,medicine ,Cell Biology ,Hematology ,medicine.symptom ,business ,Biochemistry ,Dermatology - Abstract
Introduction Monoclonal gammopathy of ocular significance (MGOS) is a rare subset of monoclonal gammopathy of clinical significance (MGCS) occurring secondary to plasma cell dyscrasia resulting in ocular manifestations. Given the rarity of these conditions, optimal management strategies are not defined; the approach is dependent upon the underlying cause of the monoclonal gammopathy and whether or not the patient's vision is affected. We report our review of 23 cases with MGOS, more specifically on paraproteinemic keratopathy (PPK) the most common form, to obtain a better understanding of the patient characteristics, diagnosis and treatments. Methods We report an international retrospective series of patients with MGOS. Data was collected on patients with MGOS:there were no other inclusion criteria besides monoclonal gammopathy with an ophthalmologic manifestation; however, this report focuses only on patients with PPK. Efficacy outcomes were the hematologic and the ocular responses in patients with PPK. Hematologic responses were reported according to the IMWG response criteria. The ophthalmologic response to treatment was assessed by each contributing physician and reported as either complete, partial or no sight recovery. Results We identified 23 patients with PPK in the setting of monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM) diagnosed between 2006 and 2019 in 7 countries. Table 1 summarizes the patients' characteristics. The ocular diagnosis was typically made at the same time or after the hematologic diagnosis. Eleven of 23 patients presented decreased vision. Four were treated by penetrating keratoplasty with or without systemic therapy, including chemotherapy with new generation anti-MM agents with or without autologous stem cell transplantation (ASCT). All patients with MM and 40% of those with other diagnoses such as SMM or MGUS received systemic therapy. In most cases, neither ocular nor hematologic treatment, even when ASCT was performed, afforded a durable improvement in the visual acuity despite initial responses. MGOS typically relapsed within one year of the initial response (Table 2). Conclusion To date, this is the largest retrospective study focusing on MGOS patients with monoclonal immunoglobulin deposits accumulating in the cornea and resulting in visual impairment. Further studies will be required to determine the optimal strategy to treat and prevent the relapse of ocular symptoms in patients with PPK and specifically to address the timing of keratoplasty and systemic chemotherapy and the role of maintenance therapy. Patients with corneal manifestation of unknown origin should undergo a hematologic check-up and patients with paraproteinemia should have a periodic ocular health assessment. Figure 1 Figure 1. Disclosures Garderet: Takeda: Consultancy; Sanofi: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Munder: Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Consultancy; GSK: Consultancy; Incyte: Research Funding. Gozzetti: AbbVie: Honoraria; Janssen: Honoraria. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Jurczyszyn: Janssen-Cilag, Amgen: Honoraria, Speakers Bureau.
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- 2021
25. Impact of Treating Facility on Overall Survival and Treatment in Multiple Myeloma (MM) Using National Cancer Database (NCDB)
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Xiaoyang Ma, Bryan Chan, Catherine Lai, Allison E. Taylor, Jaeil Ahn, Kimberley Doucette, and David H. Vesole
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cancer ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Internal medicine ,medicine ,Overall survival ,business ,Multiple myeloma - Abstract
Introduction: Prior studies have shown poorer outcomes in Black and Hispanic patients and in patients with lower median household income and education 1-5. In MM, we hypothesize that facility affiliation and case volume affects overall survival (OS) and rates of frontline treatment (including chemotherapy, immunotherapy, autologous stem cell transplant [ASCT] and palliative care). Methods: This is a retrospective analysis of 174,551 MM patients in the NCDB database, over the age of 18 years, between 2004-2016. Facility types include community cancer programs, comprehensive community cancer programs, academic/research cancer programs and integrated network cancer programs. High volume facilities had new MM cases per year ≥ 99 th percentile, and all other facilities were classified as low volume. Multivariable analyses used Cox proportional hazard analysis for OS and logistic regression for use of treatment, adjusted for age, sex, race, Hispanic origin, education, great circle distance, CCI score, and type of county (depending on population size). Kaplan-Meier method was used to estimate median OS, and the log rank test was used to compare OS across predictor variables. Results: The median age was 67 years (range 18-90) with 55% males, and 76% White vs 20% Black. In academic/research cancer programs, the median OS in high volume centers was 75.5 mo vs 50.2 mo in low volume centers (p Discussion: Our results show that academic/research cancer programs with high volumes have the best OS in MM. Additionally, academic/research cancer programs are more likely to give chemotherapy, immunotherapy, and ASCT, but less likely to give palliative care. We theorize that academic/research cancer programs with a high volume of cases likely have increased resources, which optimizes outcomes. Given that ~25% of patients with MM die in the first year 6, there is a recognized need to identify strategies to improve early outcomes in patients treated at community cancer programs and low volume facilities. Figure 1 Figure 1. Disclosures Lai: Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Speakers Bureau; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Speakers Bureau; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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- 2021
26. Inferior Outcomes of Patients with Quad and Penta-Refractory Multiple Myeloma (MM) Compared to Those of Patients Who Have Been Quad and Penta Exposed
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Sarvarinder K Gill, Rashmi Unawane, Shuqi Wang, Adolfo Aleman, Michelle Serna, Fideliza Perez-Manon, Gina Rivieccio, David S. Siegel, David H. Vesole, Harsh Parmar, Jaeil Ahn, and Noa Biran
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
Background: Despite significant advancements in MM therapies, patients with quad-refractoriness (refractory to proteasome inhibitors: bortezomib and carfilzomib, and immunomodulatory drugs: lenalidomide and pomalidomide) and penta-refractoriness (additional refractoriness to CD-38+ monoclonal antibody daratumumab) have a poor prognosis in terms of short progression-free survival (PFS) and overall survival (OS). This is a retrospective, single institutional study comparing the outcomes of patients with quad and penta-refractory MM to patients who were quad and penta-exposed, but not refractory. Methods: Consecutive patients from the John Theurer Cancer Center at Hackensack Meridian School of Medicine who were quad and penta-exposed and/or refractory between the dates of 1/1/2015 and 3/1/2021 were identified. Quad-exposed was defined as having had prior exposure to bortezomib, carfilzomib, lenalidomide and pomalidomide. Penta-exposed was defined as having prior exposure to bortezomib, carfilzomib, lenalidomide and pomalidomide and daratumumab. Penta or quad refractory was defined as having stable disease (as best response) or progressive disease while on all of the above drugs, per International Myeloma Working Group (IMWG) definition of refractory. Patients were excluded if they had missing data or if they did not meet the above definitions. Baseline characteristics, high-risk status, ISS, treatment history, treatment response, drugs at first relapse and survival outcomes were obtained retrospectively from the electronic medical record and entered into database. High-risk cytogenetics were defined as the presence of t(4;14), t(14;16) or del 17p; 1q21 gain or amplification; 1p del; t(6;14); t(14;20). Baseline patients' characteristics were summarized descriptively by quad and penta-exposed groups. PFS and OS were estimated using the Kaplan-Meier method. Univariate and multivariable adjusted Cox proportional hazard regression models examined factors affecting OS. Results: A total of 162 patients met the inclusion criteria: 18/162 (11%) were quad or penta-exposed, 32/162 (20%) were quad-refractory, and 112/162 (69%) were penta-refractory. Median age was 62 (55-69), IgG subtype (59%), and 62/162 (38.5%) had high-risk cytogenetics. The median number of lines prior was 6 (range 4-8) among all patients, and 7 (range 5-9) in the penta-refractory group. 133/162 (82.1%) had prior autologous-stem cell transplant (ASCT). Extramedullary disease was present in 40/162 (25.2%). Plasma cell leukemia was present in 14/162 (8.8%). For those who were penta-refractory, the median time from quad to penta-refractory status was 10.2 months (95% confidence interval (CI), 3.57-16.57). See Table 1. Figure 1 shows PFS and OS from the time of becoming quad or penta-exposed or refractory (T0 ). The median PFS after T0 was 11.86 months (95% CI, 6.5-26.6) for combined quad and penta-exposed, compared to 3.88 months (95% CI, 2.99-5.17) for quad and penta-refractory patients. With a median follow-up of 5.14 months (Range, 0-52.4), the median OS for all patients was 7.43 months (95% CI, 5.8- 12.94). (Figure 1A). With a median follow-up time of 4.45 months (Range, 0-52.38), the median OS for patients who were quad or penta-refractory was 5.97 months [95% CI. 4.44-8.23], compared to OS not reached (NR) for quad or penta-exposed, with a median follow-up of 11.86 months. (Figure 1B). At least one subsequent treatment regimen was employed after T0 in 85% of the patients. (Figure 1C). Multivariable adjusted analysis (Table 2) revealed that patients ≥62 had inferior OS compared to those < 62 (p -value=0.046). Furthermore, patients who had ≤10 months between becoming quad- and penta-refractory had inferior OS compared to patients with >10 months (p=0.031). OS was not significantly affected by high risk versus standard cytogenetics or drugs used at first relapse. Conclusion: MM patients with quad and penta-refractory disease have significantly worse outcomes compared to patients with quad and penta-exposed MM: older age (> 62 years) and a short interval (< 10 months) between becoming quad and penta-refractory confer an adverse prognosis. Prospective studies are required to confirm these findings. Penta and quad-refractory multiple myeloma continues to represent a vulnerable population with an unmet need for therapeutic approaches. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
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