413 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. Gene expression profiling impacts treatment decision making in newly diagnosed multiple myeloma patients in the prospective PROMMIS trial
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Noa Biran, Binod Dhakal, Suzanne Lentzsch, David Siegel, Saad Z. Usmani, Adriana Rossi, Cara Rosenbaum, Divaya Bhutani, David H. Vesole, Cesar Rodriguez, Ajay K. Nooka, Frits vanRhee, Lisette Stork‐Sloots, Femke deSnoo, Pritish K. Bhattacharyya, Durga Prasad Dash, Sena Zümrütçü, Martin H. vanVliet, Parameswaran Hari, and Ruben Niesvizky
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clinical trials ,gene arrays ,gene expression ,multiple myeloma ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Multiple myeloma (MM) is a heterogeneous hematologic malignancy associated with several risk factors including genetic aberrations which impact disease response and survival. Thorough risk classification is essential to select the best clinical strategy to optimize outcomes. The SKY92 molecular signature classifies patients as standard‐ or high‐risk for progression. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) measures impact of SKY92 on risk classification and treatment plan. Newly diagnosed MM patients had bone marrow aspirates analyzed for SKY92. Physicians completed a questionnaire for each patient capturing risk classification, hypothetical treatment plan, and physician confidence in the treatment plan, before and after unblinding SKY92. One hundred forty seven MM patients were enrolled. Before unblinding SKY92, physicians regarded 74 (50%) patients as clinical standard‐risk. After unblinding SKY92, 16 patients were re‐assigned as high‐risk by the physician, and for 15 of them treatment strategy was impacted, resulting in an escalated treatment plan. For the 73 (50%) clinical high‐risk patients, SKY92 indicated 46 patients to be standard‐risk; for 31 of these patients the treatment strategy was impacted consistent with a de‐escalation of risk. Overall, SKY92 impacted treatment decisions in 37% of patients (p
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- 2021
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6. Plasma Cell Leukemia – Facts and Controversies: More Questions than Answers?
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Anna Suska, David H. Vesole, Jorge J. Castillo, Shaji K. Kumar, Hari Parameswaran, Maria V. Mateos, Thierry Facon, Alessandro Gozzetti, Gabor Mikala, Marta Szostek, Joseph Mikhael, Roman Hajek, Evangelos Terpos, and Artur Jurczyszyn
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Plasma cell leukemia ,plasma cell dyscrasia ,chemotherapy ,novel agents ,stem cell transplantation ,clinical trials ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Plasma cell leukemia (PCL) is an aggressive hematological malignancy characterized by an uncontrolled clonal proliferation of plasma cells (PCs) in the bone marrow and peripheral blood. PCL has been defined by an absolute number of circulating PCs exceeding 2.0 × 109/L and/or >20% PCs in the total leucocyte count. It is classified as primary PCL, which develops de novo, and secondary PCL, occurring at the late and advanced stages of multiple myeloma (MM). Primary and secondary PCL are clinically and biologically two distinct entities. After the diagnosis, treatment should be immediate and should include a proteasome inhibitor and immunomodulator-based combination regimens as induction, followed by stem cell transplantation (SCT) in transplant-eligible individuals who have cleared the peripheral blood of circulating PCs. Due to the rarity of the condition, there have been very few clinical trials. Furthermore, virtually all of the myeloma trials exclude patients with active PCL. The evaluation of response has been defined by the International Myeloma Working Group and consists of both acute leukemia and MM criteria. With conventional chemotherapy, the prognosis of primary PCL has been ominous, with reported overall survival (OS) ranging from 6.8 to 12.6 months. The use of novel agents and autologous SCT appears to be associated with deeper response and an improved survival, although it still remains low. The PCL prognostic index provides a simple score to risk-stratify PCL. The prognosis of secondary PCL is extremely poor, with OS of only 1 month.
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- 2020
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7. Carfilzomib, lenalidomide, and low-dose dexamethasone in elderly patients with newly diagnosed multiple myeloma
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Dominik Dytfeld, Jagoda Jasielec, Kent A. Griffith, Daniel Lebovic, David H. Vesole, Sundar Jagannath, Ammar Al-Zoubi, Tara Anderson, Kristen Detweiler-Short, Keith Stockerl-Goldstein, Asra Ahmed, Terri Jobkar, Diane E. Durecki, Kathryn McDonnell, Melissa Mietzel, Daniel Couriel, Mark Kaminski, Ravi Vij, and Andrzej J. Jakubowiak
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2014
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8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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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15. 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
16. The importance of cytogenetic and molecular aberrations in multiple myeloma
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Anna Suska, Grzegorz Charliński, David H. Vesole, and Artur Jurczyszyn
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Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Karyotype ,Hematology ,medicine.disease ,Malignancy ,Patient care ,Clinical Practice ,Internal medicine ,medicine ,business ,Staging system ,Multiple myeloma ,Fluorescence in situ hybridization - Abstract
Multiple myeloma (MM) is a heterogeneous clonal malignancy of plasma cells characterized by cytogenetic and molecular abnormalities. Chromosomal abnormalities are present at diagnosis and can evolve during the progression of MM. Metaphase karyotyping and fluorescence in situ hybridization are considered the standard diagnostic procedures performed in clinical practice. These test results are required to determine the Revised International Staging System classification, treatment algorithms, and short- and long-term prognoses. Given the dynamic development of cytogenetic and molecular research, we should expect further progress in better understanding the biology of MM and changes to patient care in the coming years.
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- 2021
17. Outcomes of upfront autologous hematopoietic cell transplantation in patients with multiple myeloma who are 75 years old or older
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Omar Davila, Muzaffar H. Qazilbash, Parameswaran Hari, Nina Shah, Pashna N. Munshi, Shaji Kumar, David H. Vesole, Andrew St. Martin, and Anita D'Souza
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Male ,Melphalan ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Oncology and Carcinogenesis ,Population ,utilization ,Hematopoietic stem cell transplantation ,Regenerative Medicine ,elderly ,Transplantation, Autologous ,Clinical Research ,Internal medicine ,medicine ,Humans ,Oncology & Carcinogenesis ,education ,hematopoietic ,Multiple myeloma ,Aged ,Transplantation ,education.field_of_study ,Proportional hazards model ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,United States ,Confidence interval ,Neoplasm Recurrence ,myeloma ,Good Health and Well Being ,Treatment Outcome ,Local ,Oncology ,Public Health and Health Services ,Female ,Neoplasm Recurrence, Local ,Multiple Myeloma ,business ,Autologous ,medicine.drug - Abstract
BACKGROUND Consolidative autologous hematopoietic stem cell transplantation (AHCT) is commonly used for patients with multiple myeloma (MM). We studied AHCT use and outcomes in patients with MM ≥75 years old. METHODS Patients with MM ≥75 years old receiving AHCT between 2013 and 2017 in the United States were identified using the Center for International Blood and Marrow Transplant Research database. Relapse and/or progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. Covariates used were age, sex, Karnofsky performance score (KPS), HCT-comorbidity index (HCT-CI), International Staging System and/or Durie-Salmon stage, high-risk cytogenetics, melphalan dose, and disease status at and 1 year after transplant. AHCT utilization rate using the Surveillance, Epidemiology, and End Results database was used to estimate specific incidence among ≥75 years old by race and gender. RESULTS Of 360 patients, 63% were male, 84% were White, 56% had KPS
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- 2021
18. Immune tolerance with combined allogeneic haplo‐identical haematopoietic stem cell transplant and renal transplant
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David S. Siegel, Kimberley Doucette, David H. Vesole, Scott D. Rowley, Michele Donato, and Neil J. Shah
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Haematopoiesis ,business.industry ,Renal transplant ,Immunology ,Medicine ,Hematology ,Haplo identical ,Stem cell ,business ,medicine.disease ,Kidney transplantation ,Immune tolerance - Published
- 2021
19. Gene expression profiling impacts treatment decision making in newly diagnosed multiple myeloma patients in the prospective PROMMIS trial
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Lisette Stork-Sloots, David S. Siegel, Martin H. van Vliet, David H. Vesole, Cara A. Rosenbaum, Femke A. de Snoo, Ajay K. Nooka, Durga Prasad Dash, Adriana C Rossi, Ruben Niesvizky, Parameswaran Hari, Cesar Rodriguez, Sena Zümrütçü, Frits van Rhee, Suzanne Lentzsch, Pritish K. Bhattacharyya, Binod Dhakal, Saad Z. Usmani, Divaya Bhutani, and Noa Biran
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Clinical trial ,Gene expression profiling ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Gene expression ,medicine ,Treatment decision making ,Newly diagnosed ,business ,medicine.disease ,Multiple myeloma - Abstract
Multiple myeloma (MM) is a heterogeneous hematologic malignancy associated with several risk factors including genetic aberrations which impact disease response and survival. Thorough risk classification is essential to select the best clinical strategy to optimize outcomes. The SKY92 molecular signature classifies patients as standard- or high-risk for progression. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) measures impact of SKY92 on risk classification and treatment plan. Newly diagnosed MM patients had bone marrow aspirates analyzed for SKY92. Physicians completed a questionnaire for each patient capturing risk classification, hypothetical treatment plan, and physician confidence in the treatment plan, before and after unblinding SKY92. One hundred forty seven MM patients were enrolled. Before unblinding SKY92, physicians regarded 74 (50%) patients as clinical standard-risk. After unblinding SKY92, 16 patients were re-assigned as high-risk by the physician, and for 15 of them treatment strategy was impacted, resulting in an escalated treatment plan. For the 73 (50%) clinical high-risk patients, SKY92 indicated 46 patients to be standard-risk; for 31 of these patients the treatment strategy was impacted consistent with a de-escalation of risk. Overall, SKY92 impacted treatment decisions in 37% of patients (
- Published
- 2021
20. From VAD to VRD
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Harsh Parmar, Noa Biran, and David H. Vesole
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Oncology ,Cancer Research ,medicine.medical_specialty ,Standard of care ,business.industry ,medicine.medical_treatment ,Hematopoietic Stem Cell Transplantation ,MEDLINE ,Hematopoietic stem cell transplantation ,Newly diagnosed ,medicine.disease ,Transplantation, Autologous ,Transplantation ,Autologous stem-cell transplantation ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Multiple Myeloma ,business ,Multiple myeloma - Abstract
High-dose therapy followed by autologous stem cell transplantation (ASCT) is considered the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM). With new treatment combinations offering the advantage of improved clinical outcomes of MM patients, the utilization of ASCT is again being addressed in the evolving treatment landscape. In this article, we review the role of frontline ASCT in the management of patients with MM.
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- 2021
21. 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
22. 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
23. 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
24. 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
25. 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
26. Clinical implications of cytogenetic and molecular aberrations in multiple myeloma
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Artur Jurczyszyn, David H. Vesole, and Sarah Goldman-Mazur
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Oncology ,medicine.medical_specialty ,business.industry ,Cytogenetics ,Chromosome ,Chromosomal translocation ,Karyotype ,Hematology ,medicine.disease ,Minimal residual disease ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,business ,Monoclonal gammopathy of undetermined significance ,Multiple myeloma - Abstract
Multiple myeloma (MM) is an incurable haematological malignancy affecting approximately 7:100,000 people. Monoclonal gammopathy of undetermined significance (MGUS) and ‘smouldering’ MM precede symptomatic MM. Cytogenetics in MM is the most powerful prognostication tool incorporated into different classifications, including the Revised International Staging System (R-ISS) and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART). Methods commonly used to test for cytogenetic aberrations include conventional karyotyping and fluorescence in situ hybridisation (FISH), although the difficulty of obtaining metaphases in plasma cells results in low yields. Therefore, new genomic tools are essential to explore the complex landscape of genetic alterations in MM. These include next generation sequencing, a highly sensitive method to monitor minimal residual disease. The serial evolution of MGUS to MM is accompanied by a range of heterogenous genetic abnormalities, divided into primary (involving mostly chromosome 14 translocations and trisomies) and secondary genetic aberration events (involving mostly 17p, 1p, 13q deletions, 1q gain, or MYC translocations). Based on the primary genetic aberration results, strong prognostic features of MM have been identified with distinct clinical characteristics. High risk aberrations include 17p deletion, t(4;14), t(14;16), t(14;20) and chromosome 1 abnormalities. The incorporation of novel drugs and maintenance strategies in conjunction with autologous stem cell transplantation partially overcome the adverse effect of some of these genetic aberrations. Nonetheless, survival remains worse in this group compared to standard risk patients. Clinical decisions regarding treatment should be based on the cytogenetic results. The establishment of individualised and mutation-targeted therapies are of the greatest importance in future studies.
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- 2021
27. A phase 1b study of once‐weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
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Amy S. Kimball, Belle Fang, Melissa Alsina, Ola Landgren, David S. Siegel, William I. Bensinger, Noopur Raje, Ruben Niesvizky, Tibor Kovacsovics, David H. Vesole, and Jesus G. Berdeja
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Oncology ,medicine.medical_specialty ,Dexamethasone ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,In patient ,Adverse effect ,Lenalidomide ,Multiple myeloma ,Research Articles ,business.industry ,Hematology ,medicine.disease ,Carfilzomib ,Regimen ,chemistry ,030220 oncology & carcinogenesis ,Cohort ,business ,Multiple Myeloma ,Oligopeptides ,030215 immunology ,medicine.drug ,Research Article - Abstract
Twice‐weekly carfilzomib with lenalidomide‐dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once‐weekly carfilzomib with Rd (once‐weekly KRd) in NDMM patients. The NDMM patients were enrolled regardless of transplant eligibility. Patients received carfilzomib on days 1, 8, and 15; lenalidomide 25 mg on days 1‐21; and dexamethasone 40 mg on carfilzomib days (also day 22 for cycles 1‐8) for ≤18, 28‐day cycles. Enrollment initiated in a carfilzomib 20/70 mg/m2 (20 mg/m2 on cycle one, day 1; 70 mg/m2 thereafter) NDMM dose‐expansion arm, which was suspended because of serious adverse events. After evaluation of dose‐limiting toxicities in a two‐step‐up dose‐evaluation cohort, an NDMM dose‐expansion arm (carfilzomib 20/56 mg/m2) was opened. Fifty‐one NDMM patients were enrolled in dose‐finding and dose‐expansion cohorts. Results are presented for the carfilzomib 56 mg/m2 NDMM dose‐expansion arm (n = 33). The grade ≥ 3 treatment‐emergent AE (TEAE) rate was 63.6%. Twenty‐five patients underwent stem cell collection; 18 proceeded to auto stem cell transplant, and five resumed KRd on study after autoSCT. The overall response rate (ORR) based on best overall response by cycle four was 97.0% (≥very good partial response [VGPR], 69.7%) in the NDMM 20/56 mg/m2 cohort. In patients who did not receive autoSCT (n = 15), the median number of cycles was 16.0; ORR was 93.3% (≥VGPR, 80.0%). At a median follow‐up of 8.1 months, median progression‐free survival was not reached. Once‐weekly KRd (carfilzomib 56 mg/m2) had a favorable safety profile and promising activity in NDMM, supporting the use of this regimen in this setting.
- Published
- 2020
28. 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
- Author
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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
- Subjects
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.
- Published
- 2022
29. 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
- Author
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Olga Czerwińska-Ledwig, David H Vesole, Wanda Pilch, Joanna Gradek, and Artur Jurczyszyn
- Abstract
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
30. Negative Impact of Borderline Creatinine Concentration and Glomerular Filtration Rate at Baseline on the Outcome of Patients With Multiple Myeloma Treated With Autologous Stem Cell Transplant
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Katarzyna Kobylinska, Pyush Vyas, Emilian Snarski, Anna Rodziewicz-Lurzynska, Anna Waszczuk-Gajda, Beata Blajer, Agnieszka Stefaniak, Jarosław Biliński, Artur Jurczyszyn, Hanna Zborowska, Magdalena Feliksbrot-Bratosiewicz, David H. Vesole, Małgorzata Król, Grzegorz W. Basak, Katarzyna Krzanowska, J. Drozd-Sokolowska, Mateusz Ziarkiewicz, Wiesław Wiktor Jędrzejczak, Paweł Kozłowski, Kamila Skwierawska, Jolanta Malyszko, Maria Król, Przemyslaw Biecek, Elżbieta Urbanowska, Jadwiga Dwilewicz-Trojaczek, Agnieszka Tomaszewska, Krzysztof Mądry, Piotr Boguradzki, and Martyna Maciejewska
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,Renal function ,Transplantation, Autologous ,chemistry.chemical_compound ,Normal renal function ,Induction therapy ,Humans ,Medicine ,Renal Insufficiency ,Multiple myeloma ,Aged ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,Creatinine ,Kidney ,Chemotherapy ,business.industry ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Female ,Surgery ,Stem cell ,Multiple Myeloma ,business ,Glomerular Filtration Rate - Abstract
Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC)2 mg/dL or estimated glomerular filtration rate (eGFR) 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria.We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR 60 mL/min, treated with ASCT from 1998 to 2004.The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC1.4 mg/dL and eGFR 55mL/min.We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency.
- Published
- 2020
31. Busulfan, melphalan, and bortezomib compared to melphalan as a high dose regimen for autologous hematopoietic stem cell transplantation in multiple myeloma: long term follow up of a novel high dose regimen
- Author
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Patrick Hagen, Mei-Jie Zhang, Parameswaran Hari, Omar Davila, David H. Vesole, Scott E. Smith, Patrick J. Stiff, Tulio E. Rodriguez, and Anita D'Souza
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Melphalan ,Oncology ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Long term follow up ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Article ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Busulfan ,Multiple myeloma ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Regimen ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Multiple Myeloma ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Melphalan at a dose of 200 mg/m(2) (MEL200) remains the standard high dose therapy before autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Intensifying the high dose regimen has shown promising results. We report here 7-year follow up of our novel high dose regimen of busulfan and melphalan followed by bortezomib (BuMelVel). Forty-three MM patients received BuMelVel high dose therapy with pharmacokinetic adjusted busulfan. Outcomes were compared to a matched control cohort from the CIBMTR database (n = 162) receiving MEL200. The primary endpoint was progression free survival. Five year PFS was 47% v 30% (95% CI; 32–62) in favor or the BuMelVel group (95% CI; 23–37) (p=0.05). In multivariate analysis for PFS, BuMelVel (HR 0.65; 95% CI 0.44–0.97)(p=0.036) was predictive. Similar to recent reports of double alkylator therapy, although depth of response was similar between the BuMelVel group and MEL200, the BUMELVEL group experienced an improved PFS.
- Published
- 2020
32. Different MAF translocations confer similar prognosis in newly diagnosed multiple myeloma patients
- Author
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Krzysztof Jamroziak, Artur Jurczyszyn, Chor Sang Chim, Monika Długosz-Danecka, Deepu Madduri, Julia Kelman, Max Bittrich, Michel Delforge, Klaus Martin Kortüm, Gabor Mikala, Ariel Kleman, Jorge J. Castillo, Maria-Victoria Mateos, Adam J. Olszewski, Saurabh Chhabra, Pawel Robak, Lidia Usnarska-Zubkiewicz, Anna Waszczuk-Gajda, Iwona Hus, Sarah Goldman-Mazur, David Jayabalan, Julio Davila Valls, Irit Avivi, Rebecca Silbermann, Norbert Grząśko, Stuart L. Goldberg, David H. Vesole, Yael C Cohen, Ruben Niesvizky, Piotr Mazur, Anna Suska, Verónica González-Calle, Laura Rosiñol, Alessandro Gozzetti, Łukasz Szukalski, Jacek Czepiel, Jakub Radocha, Parameswaran Hari, Daniel Coriu, Izabela Kozłowska, Aimee Chappell, Peter Barth, and Massimo Gentile
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Translocation ,Chromosomal translocation ,Newly diagnosed ,Transplantation, Autologous ,survival ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Multiple myeloma ,Retrospective Studies ,16) ,MAF ,myeloma ,t(14 ,20) ,business.industry ,Hematopoietic Stem Cell Transplantation ,Small sample ,Hematology ,Prognosis ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,Multiple Myeloma ,business ,Large group ,030215 immunology - Abstract
The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) (
- Published
- 2020
33. 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
34. 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
- Subjects
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.
- Published
- 2022
35. Supportive care in multiple myeloma
- Author
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Artur Jurczyszyn, Grzegorz Charliński, and David H. Vesole
- Subjects
Oncology ,Hematology - Published
- 2022
36. Pembrolizumab, lenalidomide and dexamethasone post autologous transplant in patients with high‐risk multiple myeloma
- Author
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Scott D. Rowley, Laura McBride, Palka Anand, Andrew L. Pecora, Noa Biran, Elli Gourna Paleoudis, Joshua Richter, Jaeil Ahn, Shuqi Wang, Rena Feinman, Robert Korngold, David S. Siegel, Kristin Ivanovski, Michele Donato, Meena Bansal, David H. Vesole, and Joshua Zenreich
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Phases of clinical research ,Hematology ,Pembrolizumab ,Neutropenia ,medicine.disease ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,Progression-free survival ,business ,Multiple myeloma ,Dexamethasone ,Lenalidomide ,medicine.drug - Abstract
Patients with high-risk multiple myeloma (hrMM) relapse after autologous stem cell transplantation (ASCT) with a median progression free survival (PFS) of 8-14 months without lenalidomide maintenance and 24-39 months with lenalidomide maintenance. We hypothesized that Pembro-Rd will prolong PFS post-ASCT in patients with hrMM compared to historical controls. This Phase II study enrolled hrMM patients with primary objective to assess the efficacy of the combination of Pembro-Rd for a total of 2 cycles and then an additional 2 cycles without dexamethasone. There were 12 evaluable subjects, as enrollment was stopped after an FDA hold. With a median follow-up of 50.7 months, the median PFS was 27.7 months. The PFS rates at years 1 and 2 are 90.9% and 63.6%, respectively. The most common adverse events were neutropenia (grade 1-3), cough, diarrhea and constipation, all grade 1 or 2. The PFS rate with fixed duration therapy was comparable to that seen with continuous dose lenalidomide, potentially offering a new post-ASCT therapeutic strategy. This article is protected by copyright. All rights reserved.
- Published
- 2021
37. Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma
- Author
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Grzegorz Charliński, David H. Vesole, and Artur Jurczyszyn
- Subjects
Drug ,Cancer Research ,medicine.drug_class ,media_common.quotation_subject ,Review ,Pharmacology ,Monoclonal antibody ,cereblon E3 ligase modulators ,immunomodulatory drugs ,medicine ,Multiple myeloma ,RC254-282 ,media_common ,Lenalidomide ,therapy ,business.industry ,Cereblon ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Pomalidomide ,medicine.disease ,Thalidomide ,multiple myeloma ,Oncology ,Tolerability ,business ,medicine.drug - Abstract
Simple Summary Due to the complex mechanism of actions, immunomodulatory drugs (IMiDs) are one of the primary drug classes used to treat multiple myeloma (MM). IMiDs are the backbone of treatment for both newly diagnosed, post-transplant maintenance, and relapsed/refractory MM. The standard of care is a combination of IMiDs, corticosteroids (e.g., dexamethasone) with either a proteasome inhibitor or a monoclonal antibody. Future management will include a quadruplet of all four drug classes. Recent clinical trials have shown that another class of cereblon inhibitors in development, Cereblon E3 ligase modulators (CELMoDs), have significant activity in MM even when refractory to approved IMiDs. Abstract Over the past two decades, the improvement in our understanding of the biology of MM and the introduction of new drug classes, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PI), and monoclonal antibodies (MoAb), have significantly improved outcomes. The first IMiD introduced to treat MM was thalidomide. The side effects observed during treatment with thalidomide initiated work on the synthesis of IMiD analogs. Subsequently, lenalidomide and pomalidomide were developed, both with different safety profiles, and they have better tolerability than thalidomide. In 2010, the cereblon (CRBN) protein was discovered as a direct target of IMiDs. By binding to CRBN, IMiDs change the substrate specificity of the CRBN E3 ubiquitin ligase complex, which results in the breakdown of internal Ikaros and Aiolos proteins. Most clinical trials conducted, both in newly diagnosed, post-transplant maintenance and relapsed/refractory MM, report a beneficial effect of IMiDs on the extension of progression-free survival and overall survival in patients with MM. Due to side effects, thalidomide is used less frequently. Currently, lenalidomide is used at every phase of MM treatment. Lenalidomide is used in conjunction with other agents such as PIs and MoAb as induction and relapsed therapy. Pomalidomide is currently used to treat relapsed/refractory MM, also with PIs and monoclonal antibodies. Current clinical trials are evaluating the efficacy of IMiD derivatives, the CRBN E3 ligase modulators (CELMoDs). This review focuses on the impact of IMiDs for the treatment of MM.
- Published
- 2021
38. Correction to: Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era
- Author
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Asad Bashey, Mohamed A. Kharfan-Dabaja, Omar Davila, Melhem Solh, Jeffrey Schriber, Keith Stockerl-Goldstein, Nosha Farhadfar, Cesar O. Freytes, Sachiko Seo, Cindy Lee, Jan Cerny, Sagar S. Patel, Miguel Angel Diaz, Robert F. Cornell, Raphael Fraser, Richard F. Olsson, Jesus G. Berdeja, Muzaffar H. Qazilbash, Leona Holmberg, Kenneth R. Meehan, Abraham S. Kanate, Saurabh Chhabra, Attaphol Pawarode, Amr Hanbali, Hillard M. Lazarus, Anita D'Souza, Taiga Nishihori, Wilson I. Gonsalves, David H. Vesole, Reinhold Munker, Gerhard C. Hildebrandt, Nina Shah, Jean A. Yared, Amer Assal, Parameswaran Hari, Sherif M. Badawy, Robert Peter Gale, Saulius Girnius, Binod Dhakal, Shahrukh K. Hashmi, Shaji Kumar, Lohith S. Bachegowda, Ruthlee Lu Bayer, Qaiser Bashir, Yvonne A. Efebera, Hemant S. Murthy, and Yago Nieto
- Subjects
Plasma cell leukemia ,Transplantation ,Cancer Research ,Leukemia ,Oncology ,Hematopoietic cell ,business.industry ,medicine ,Cancer research ,Hematology ,medicine.disease ,business ,Article - Published
- 2021
39. A phase I/II study of escalating doses of thalidomide in conjunction with bortezomib and high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma
- Author
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David H. Vesole, David S. Siegel, Andrew Pecora, Alan P Skarbnik, Shijia Zhang, Joshua Richter, Scott D. Rowley, Noa Biran, and Michele L. Donato
- Subjects
Adult ,Male ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,Gastroenterology ,Disease-Free Survival ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Mucositis ,Humans ,Autografts ,Multiple myeloma ,Aged ,Transplantation ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Thalidomide ,Survival Rate ,Regimen ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,business ,030215 immunology ,medicine.drug - Abstract
A regimen of escalating doses of thalidomide, in combination with bortezomib and high-dose melphalan (mel/vel/thal), was evaluated as a conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with a prior transplant who had relapsed or achieved less than a complete remission following a prior ASCT. Thalidomide was dose escalated starting from 600 mg to 1000 mg on days −5 to −1 in a 3 × 3 design, bortezomib was administered at 1.6 mg/m2 intravenously on days −4 and −1 and melphalan 200 mg/m2 was administered on day −2. No dose-limiting toxicity was seen in the phase I portion of the trial. An additional 20 patients were enrolled at the maximum tolerated dose of thalidomide of 1000 mg daily. The overall response rate was 69% with 38% complete remission. Median PFS and OS were 9.3 and 65.4 months, respectively, with a median follow-up of 17.8 months. The most common grade 3–4 adverse events (AEs) were neutropenic fever (58.6%), mucositis (6.9%), and diarrhea (6.9%). Serious AEs included somnolence (13.8%) and tumor lysis syndrome (3.4%). The addition of high-dose thalidomide to bortezomib and melphalan as conditioning for salvage ASCT was well tolerated and was an effective conditioning regimen.
- Published
- 2019
40. Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial
- Author
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Amrita Krishnan, Nancy L. Geller, Ravi Vij, Sergio Giralt, Mary M. Horowitz, S. Ganguly, Cristina Gasparetto, Beth Blackwell, Yvonne A. Efebera, Marcelo C. Pasquini, Claudio G. Brunstein, Dan T. Vogl, Edward A. Stadtmauer, Kristin Knust, Parameswaran Hari, Steven M. Devine, David H. Vesole, Philip L. McCarthy, Heather Landau, Nina Shah, George Somlo, Courtney Nelson, John Koreth, Muzaffar H. Qazilbash, and Asad Bashey
- Subjects
Male ,Oncology ,Melphalan ,Cancer Research ,Time Factors ,Dexamethasone ,Bortezomib ,Maintenance therapy ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Lenalidomide ,Multiple myeloma ,Cancer ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,ORIGINAL REPORTS ,Hematology ,Middle Aged ,Progression-Free Survival ,6.1 Pharmaceuticals ,Disease Progression ,Female ,Multiple Myeloma ,Autologous ,medicine.drug ,Reoperation ,Adult ,medicine.medical_specialty ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Oncology and Carcinogenesis ,Transplantation, Autologous ,Maintenance Chemotherapy ,Young Adult ,Rare Diseases ,Clinical Research ,Internal medicine ,medicine ,Humans ,Autologous transplantation ,Oncology & Carcinogenesis ,Progression-free survival ,Aged ,Transplantation ,business.industry ,Evaluation of treatments and therapeutic interventions ,Consolidation Chemotherapy ,Myeloablative Agonists ,medicine.disease ,United States ,Good Health and Well Being ,business - Abstract
PURPOSE Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression. PATIENTS AND METHODS Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS. RESULTS The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms. CONCLUSION Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.
- Published
- 2019
41. TTI-622-01: A phase 1a/1b dose-escalation and expansion trial of TTI-622 in patients with advanced hematologic malignancies, including multiple myeloma
- Author
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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
- Subjects
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.
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- 2022
42. Patient-reported outcomes following autologous stem cell transplant for patients with multiple myeloma
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David H. Vesole, Arnold L. Potosky, Susan Kumka, Jeanne S. Mandelblatt, David S. Siegel, Kristi D. Graves, Wanting Zhai, Rashmi Unawane, Noa Biran, and Roxanne E. Jensen
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Oncology ,medicine.medical_specialty ,Quality of life (healthcare) ,business.industry ,Internal medicine ,medicine ,Stem cell ,medicine.disease ,business ,Multiple myeloma - Abstract
We evaluated changes in patient-reported outcomes and cognitive function from pre- to 3-6 months post-treatment among 42 newly diagnosed patients with multiple myeloma undergoing transplant with complete data using PROMIS-29. There were statistically significant improvements in physical (
- Published
- 2021
43. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group
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Mario Boccadoro, Peter Leif Bergsagel, Noopur Raje, Xavier Leleu, Cristina João, Joseph R. Mikhael, Monika Engelhardt, Brian G.M. Durie, Sarah A. Holstein, Heinz Ludwig, Parameswaran Hari, Gordon Cook, Anders Waage, Maria-Victoria Mateos, Ulf-Henrik Mellqvist, Hareth Nahi, Faith E. Davies, Jian Hou, Angelo Maiolino, Saad Z. Usmani, Nizar J. Bahlis, Wee Joo Chng, Sigurdur Y. Kristinsson, Fernando Leal da Costa, Hartmut Goldschmidt, Evangelos Terpos, Pieter Sonneveld, Dominik Dytfeld, Artur Jurczyszyn, Michele Cavo, Fredrik Schjesvold, Meletios A. Dimopoulos, Jacob P. Laubach, Jesus San Miguel, Kwee Yong, Elena Zamagni, Orhan Sezer, Martin Kaiser, Surbhi Sidana, Vania Hungria, Meral Beksac, Enrique M. Ocio, Nikhil C. Munshi, Kenneth C. Anderson, Katja Weisel, Thierry Facon, Annette Juul Vangsted, Christoph Driessen, Hermann Einsele, Luciano J. Costa, Shaji Kumar, Paul G. Richardson, Philippe Moreau, Jesus G. Berdeja, Roman Hájek, Thomas G. Martin, Sagar Lonial, David H. Vesole, Rafael Fonseca, Suzanne Lentzsch, Eloisa Riva, Simon J. Harrison, Hang Quach, Rachid Baz, S. Vincent Rajkumar, Niels W.C.J. van de Donk, Joan Bladé, Jean-Luc Harousseau, Sonja Zweegman, Moreau P., Kumar S.K., San Miguel J., Davies F., Zamagni E., Bahlis N., Ludwig H., Mikhael J., Terpos E., Schjesvold F., Martin T., Yong K., Durie B.G.M., Facon T., Jurczyszyn A., Sidana S., Raje N., van de Donk N., Lonial S., Cavo M., Kristinsson S.Y., Lentzsch S., Hajek R., Anderson K.C., Joao C., Einsele H., Sonneveld P., Engelhardt M., Fonseca R., Vangsted A., Weisel K., Baz R., Hungria V., Berdeja J.G., Leal da Costa F., Maiolino A., Waage A., Vesole D.H., Ocio E.M., Quach H., Driessen C., Blade J., Leleu X., Riva E., Bergsagel P.L., Hou J., Chng W.J., Mellqvist U.-H., Dytfeld D., Harousseau J.-L., Goldschmidt H., Laubach J., Munshi N.C., Gay F., Beksac M., Costa L.J., Kaiser M., Hari P., Boccadoro M., Usmani S.Z., Zweegman S., Holstein S., Sezer O., Harrison S., Nahi H., Cook G., Mateos M.-V., Rajkumar S.V., Dimopoulos M.A., Richardson P.G., and Hematology
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medicine.medical_specialty ,Line of therapy ,Drug Resistance ,Salvage therapy ,Antineoplastic Agents ,030204 cardiovascular system & hematology ,Antineoplastic Agent ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Multiple myeloma ,Salvage Therapy ,Hematology ,business.industry ,Cancer ,Refractory Multiple Myeloma ,medicine.disease ,Drug access ,Clinical research ,Neoplasm Recurrence ,Oncology ,Local ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Neoplasm ,Multiple Myeloma ,Neoplasm Recurrence, Local ,business ,Human - Abstract
This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.
- Published
- 2021
44. Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations
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Laura Rosiñol, Meral Beksac, Elena Zamagni, Niels W. C. J. Van de Donk, Kenneth C. Anderson, Ashraf Badros, Jo Caers, Michele Cavo, Meletios‐Athanasios Dimopoulos, Angela Dispenzieri, Hermann Einsele, Monika Engelhardt, Carlos Fernández de Larrea, Gösta Gahrton, Francesca Gay, Roman Hájek, Vania Hungria, Artur Jurczyszyn, Nicolaus Kröger, Robert A. Kyle, Fernando Leal da Costa, Xavier Leleu, Suzanne Lentzsch, Maria V. Mateos, Giampaolo Merlini, Mohamad Mohty, Philippe Moreau, Leo Rasche, Donna Reece, Orhan Sezer, Pieter Sonneveld, Saad Z. Usmani, Karin Vanderkerken, David H. Vesole, Anders Waage, Sonja Zweegman, Paul G. Richardson, Joan Bladé, Rosinol L., Beksac M., Zamagni E., Van de Donk N.W.C.J., Anderson K.C., Badros A., Caers J., Cavo M., Dimopoulos M.-A., Dispenzieri A., Einsele H., Engelhardt M., Fernandez de Larrea C., Gahrton G., Gay F., Hajek R., Hungria V., Jurczyszyn A., Kroger N., Kyle R.A., Leal da Costa F., Leleu X., Lentzsch S., Mateos M.V., Merlini G., Mohty M., Moreau P., Rasche L., Reece D., Sezer O., Sonneveld P., Usmani S.Z., Vanderkerken K., Vesole D.H., Waage A., Zweegman S., Richardson P.G., Blade J., Hematology, R&D centraal, and Basic (bio-) Medical Sciences
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Oncology ,paraskeletal plasmacytomas ,Dexamethasone ,Bortezomib ,0302 clinical medicine ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,extramedullary disease ,Lenalidomide ,Multiple myeloma ,Etoposide ,education.field_of_study ,treatment ,Hematopoietic Stem Cell Transplantation ,Disease Management ,Hematology ,multiple myeloma ,plasmacytoma ,prognosis ,soft tissue ,030220 oncology & carcinogenesis ,medicine.drug ,Human ,medicine.medical_specialty ,Prognosi ,Population ,Transplantation, Autologous ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,paraskeletal plasmacytoma ,education ,Cyclophosphamide ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Animal ,medicine.disease ,Thalidomide ,Regimen ,Doxorubicin ,Proteasome inhibitor ,Plasmacytoma ,Cisplatin ,business ,030215 immunology - Abstract
In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.
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- 2021
45. Safety and Efficacy of Consolidation Therapy with Ipilimumab Plus Nivolumab after Autologous Stem Cell Transplantation
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Alan P Skarbnik, Paul Fields, Pashna N. Munshi, Michele L. Donato, Scott D. Rowley, Joshua Zenreich, Tatyana Feldman, Andrew L. Pecora, David H. Vesole, Lori A. Leslie, Dante B. Descalzi-Montoya, Andre Goy, Noa Biran, Themba Nyirenda, Rena Feinman, and Robert Korngold
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Ipilimumab ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,education ,Multiple myeloma ,Transplantation ,education.field_of_study ,business.industry ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,medicine.disease ,Lymphoma ,Consolidation Chemotherapy ,Nivolumab ,Molecular Medicine ,Neoplasm Recurrence, Local ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Autologous hematopoietic stem cell transplantation (ASCT) is a standard-of-care treatment for many hematologic malignancies. Progression of disease after ASCT is the primary cause of treatment failure. In this Phase Ib trial, we studied the safety and clinical effect of combined checkpoint inhibition therapy (CPIT) with ipilimumab and nivolumab as a consolidation strategy after ASCT for patients with high-risk diffuse large B cell lymphoma (DLBCL), mature T cell lymphoma (TCL), and multiple myeloma (MM). Starting at 14 to 28 days after ASCT, patients received ipilimumab (1 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 16, and 22) and nivolumab (3 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, and 26). Patients received a median of 5 doses of ipilimumab and 8 doses of nivolumab. Thirty-five patients were included in the intent-to-treat population. Ninety-four percent of the patients experienced immune-related adverse events (irAEs) of any grade. Ninety-seven percent of irAEs resolved spontaneously or after holding study drugs and instituting high-dose corticosteroid therapy. Progression-free and overall survival at 18 months post-ASCT for each disease cohort were 85.7% and 100% for primary refractory DLBCL, 28.6% and 57.1% for relapsed DLBCL, not evaluable and 80% for frontline TCL, 25% and 75% for relapsed TCL, 57.1% and 87% for high-risk transplant-naive MM, and 40% and 100% for MM relapsed within 3 years of first ASCT. We conclude that combined CPIT appears to be tolerable as a consolidation strategy after ASCT and in addition to the potential clinical efficacy observed in some subsets of disease, T cell receptor repertoire, T regulatory cell phenotype, and gut microbiota profiles provide a biologic rationale warranting further study of this approach.
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- 2020
46. Prevalence and Survival Impact of Self-Reported Symptom and Psychological Distress Among Patients With Multiple Myeloma
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Victoria DeVincenzo, Joshua Richter, Brooke Grunman, David S. Siegel, Noa Biran, Andrew L. Pecora, Kathryn Tanenbaum, Larysa Sanchez, Ching-Kun Wang, David H. Vesole, and Stuart L. Goldberg
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Cancer Research ,medicine.medical_specialty ,Palliative care ,Plasma cell dyscrasia ,Psychological Distress ,03 medical and health sciences ,0302 clinical medicine ,Cancer Survivors ,Internal medicine ,Surveys and Questionnaires ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Survival rate ,Multiple myeloma ,Depression (differential diagnoses) ,Performance status ,business.industry ,Palliative Care ,Hematology ,medicine.disease ,Prognosis ,Distress ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Self Report ,Symptom Assessment ,business ,Multiple Myeloma ,Psychosocial - Abstract
Background Advances in the management of multiple myeloma (MM) have extended survival and reduced painful skeletal-related events. As MM is evolving toward a chronic disease, we sought to determine the prevalence of self-reported symptom burden and psychological distress, and to determine the association of distress with survival. Methods The CPASS-7 patient-reported outcome instrument was administered to a convenience sample of MM patients at 7 outpatient cancer centers. Results A total of 239 patients completed the CPASS-7 between September 2015 and October 2016%; 57% of respondents were male, and median age was 67 years. Forty-eight percent were concerned that they could not do the things they wanted to do, with 33% reporting decreased performance status. Financial toxicity concerns were self-reported by 44%, with family burdens noted in 24%. Although depression was reported by only 15%, 41% noted lack of pleasure. Pain was a concern in 36%. With a median follow-up of 316 days since CPASS-7 completion, 13% of patients had died. A high total distress score was noted in 57 (24%) and trended toward an association with a decreased survival rate compared to the 182 patients (76%) with a low total distress score (P = .066). The 6-month survival rates for patients with high and low distress scores were 86% and 96%, respectively, and 12-month survival rates were 76% and 87%, respectively. Conclusion Despite dramatic improvements in survival among patients with MM, symptom, financial, and psychosocial concerns continue to be major patient concerns. As MM becomes a chronic disease, additional attention to addressing these issues is required.
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- 2020
47. Autologous Transplants for Multiple Myeloma
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N. C. Munshi, Sundar Jagannath, B. Barlogie, D. Siegel, Guido Tricot, and David H. Vesole
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,business ,medicine.disease ,Multiple myeloma - Published
- 2020
48. Age no bar: A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma
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Gunjan L. Shah, Sherif M. Badawy, Nosha Farhadfar, Jason Tay, Mohamed A. Kharfan-Dabaja, Shaji Kumar, Minoo Battiwalla, Sachiko Seo, Rebecca L. Olin, Kenneth R. Meehan, Parameswaran Hari, Richard F. Olsson, Pashna N. Munshi, Muzaffar H. Qazilbash, Maxwell M. Krem, Hemant S. Murthy, Artur Jurczyszyn, Anita D'Souza, Jeffrey Schriber, Saurabh Chhabra, Siddhartha Ganguly, Vaibhav Agrawal, Omar Davila, Melhem Solh, Taiga Nishihori, Hillard M. Lazarus, Ehsan Malek, Nina Shah, Andrew St. Martin, Jan Maciej Zaucha, Shahrukh K. Hashmi, David H. Vesole, and Edward A. Copelan
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Melphalan ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,Transplantation, Autologous ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Multiple myeloma ,Aged ,Aged, 80 and over ,Dose-Response Relationship, Drug ,business.industry ,Proportional hazards model ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Confidence interval ,Progression-Free Survival ,United States ,Transplantation ,Treatment Outcome ,Oncology ,Geriatric oncology ,030220 oncology & carcinogenesis ,Female ,Neoplasm Recurrence, Local ,business ,Multiple Myeloma ,medicine.drug - Abstract
BACKGROUND Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. METHODS The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value
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- 2020
49. Real-world prognostic factors in autotransplanted multiple myeloma patients with severe renal impairment: study of the Polish Myeloma Study Group
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Jolanta Malyszko, Wiesław Wiktor Jędrzejczak, David H. Vesole, Tomasz Wróbel, Joanna Drozd-Sokołowska, Jarosław Biliński, Piotr Boguradzki, Magdalena Olszewska-Szopa, Artur Jurczyszyn, Grzegorz W. Basak, Maria Król, Anna Waszczuk-Gajda, Longin Niemczyk, Agnieszka Tomaszewska, and Krzysztof Mądry
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Oncology ,medicine.medical_specialty ,Autologous stem-cell transplantation ,business.industry ,medicine.medical_treatment ,Internal medicine ,medicine ,General Medicine ,business ,medicine.disease ,Dialysis ,Multiple myeloma - Abstract
IntroductionThe prognostic factors in autotransplanted multiple myeloma (MM) patients with concomitant advanced chronic kidney disease (CKD) are poorly understood, limited, and controversial.Material and methodsWe retrospectively analysed 44 patients with MM and CKD (eGFR < 40 ml/min), present both at diagnosis and at autologous stem cell transplantation (ASCT), with no improvement of renal function in-between.ResultsPatients exhibiting deeper paraprotein responses to pre-transplant treatment predicted better response post ASCT (odds ratio (OR) = 11.6, p = 0.028) and longer progression-free survival (PFS) (hazard ratio (HR) = 0.23, p = 0.017). Higher albumin concentration (per increase of 1 g/dl) (HR = 0.41, p = 0.03) and melphalan 140 mg/m2 versus higher melphalan doses (HR = 0.86, p = 0.008) were associated with longer PFS. Performance status (ECOG 0-1 versus ≥ 2) (HR = 0.28, p = 0.0036), higher albumin concentration (HR = 0.43, p < 0.037), and melphalan 140 mg/m2 versus higher melphalan doses (HR = 0.48, p = 0.081) decreased the risk of death. Three of 32 dialysis-dependent patients became dialysis independent (DID), and 5 of 12 in the DID group had eGFR improvement post ASCT. The median PFS was 2.3 years, which was shorter for DID compared to DD patients (0.7 vs. 3.3 years, respectively). The median overall survival (OS) was 3.6 years, there was no difference in median OS between the groups (4.0 vs. 3.5 years, respectively).ConclusionsOptimal patient selection including good performance status and higher albumin concentration (with every increase of 1 g/dl), chemotherapy-responsive disease pre-ASCT, melphalan dose adjusted to CKD, and intensive post-transplant supportive care are crucial to achieve acceptable results of treatment of MM patients with CKD.
- Published
- 2020
50. African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States
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Mohamed A. Kharfan-Dabaja, Baldeep Wirk, Hillard M. Lazarus, Nina Shah, Heather Landau, Hemant S. Murthy, Qaiser Bashir, Taiga Nishihori, Kenneth R. Meehan, Nosha Farhadfar, David H. Vesole, Talha Badar, Melhem Solh, Raphael Fraser, Reinhold Munker, Binod Dhakal, Yago Nieto, Jesus G. Berdeja, Cindy Lee, Natalie S. Callander, Parameswaran Hari, Ehsan Malek, Robert A. Kyle, Saurabh Chhabra, Cesar O. Freytes, Shahrukh K. Hashmi, Omar Davila, Sundar Jagannath, Gerhard C. Hildebrandt, Ravi Vij, Shaji Kumar, Miguel Angel Diaz, Siddhartha Ganguly, Rammurti T. Kamble, Anita D'Souza, and Cesar Rodriguez Valdes
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Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Transplantation Conditioning ,Chromosomal translocation ,Transplantation, Autologous ,Article ,Translocation, Genetic ,White People ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Stage (cooking) ,Multiple myeloma ,Hematopoietic cell ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Confidence interval ,United States ,Transplantation ,Black or African American ,030220 oncology & carcinogenesis ,Female ,business ,Multiple Myeloma - Abstract
Background Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. Methods This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). Results African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. Conclusions Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.
- Published
- 2020
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