54 results on '"Elvira Umyarova"'
Search Results
2. Modified carfilzomib dosing is associated with improved treatment responses and longer time on treatment in patients with multiple myeloma
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Abdullah M. Khan, Kiatlyn Dvorak, Qiuhong Zhao, Naresh Bumma, Francesca Cottini, Srinivas Devarakonda, Elvira Umyarova, Nidhi Sharma, Don Benson, and Ashley Rosko
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Impact of interval progression before autologous stem cell transplant in patients with multiple myeloma
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Alicia Bao, Qiuhong Zhao, Ruchi Kudalkar, Jose Rodriguez, Nidhi Sharma, Naresh Bumma, Srinivas S. Devarakonda, Abdullah M. Khan, Elvira Umyarova, Ashley E. Rosko, Don Benson, and Francesca Cottini
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myeloma ,stem cell transplant (SCT) ,outcome ,immune profiling ,disease progression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In transplant-eligible patients who undergo upfront autologous stem cell transplant (ASCT) for multiple myeloma (MM), standard practice is to treat with six to eight cycles of induction therapy followed by high-dose chemotherapy with ASCT. A gap between the end of induction and the day of ASCT exists to allow stem cell mobilization and collection. Despite attempts to limit the length of this interval, we noticed that some patients experience interval progression (IP) of disease between the end of induction therapy and the day of ASCT. We analyzed 408 MM patients who underwent ASCT between 2011 and 2016. The median length of the interval between end of induction and ASCT was 38 days. We observed that 26% of patients in the entire cohort and 23.6% of patients who received induction with bortezomib-lenalidomide-dexamethasone (VRD) experienced IP. These patients deepened their responses with ASCT, independently of induction regimen. In the entire cohort, IP was significantly associated with shorter PFS in the univariable analysis (Hazard Ratio, HR = 1.37, P = 0.022) but not in the multivariable analysis (HR = 1.14, P = 0.44). However, analyzing only patients who received VRD as induction, progression-free survival (PFS) remained inferior in both the univariable (HR = 2.02; P = 0.002) and the multivariable analyses (HR = 1.96; P = 0.01). T cells and natural killer (NK) cells are increasingly studied targets of immunomodulatory therapy, as immune dysfunction is known to occur in patients with MM. Peripheral blood from 35 MM patients were analyzed. At time of ASCT, patients with IP had significantly increased percentages of CD3+CD8+CD57+ CD28- (P = 0.05) and CD3+CD4+LAG3+ (P = 0.0022) T-cells, as well as less CD56bright and CD56dim NK cells bearing activated markers such as CD69, NKG2D, and CD226. These data suggest that IP can impact the length of response to ASCT; therefore, further studies on the management of these patients are needed.
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- 2023
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4. Racial differences as predictors of outcomes in young patients with multiple myeloma
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Alicia Bao, Qiuhong Zhao, Elizabeth Merritt, Naresh Bumma, Srinivas Devarakonda, Abdullah M. Khan, Elvira Umyarova, Ashley E. Rosko, Don M. Benson, and Francesca Cottini
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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5. Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study
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Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K. Moyo, Nishitha Reddy, Julia Sheets, David M. Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C. Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F. Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A. David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P. Kenkre, Adam J. Olszewski, Jonathon B. Cohen, Neil Palmisiano, Elvira Umyarova, Ryan A. Wilcox, Farrukh T. Awan, Juan Pablo Alderuccio, Stefan K. Barta, Natalie S. Grover, Nilanjan Ghosh, Nancy L. Bartlett, Alex F. Herrera, and Geoffrey Shouse
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Marginal zone lymphoma ,MZL ,Ibrutinib ,Relapsed ,Refractory ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: “ibrutinib responders”—patients who achieved complete or partial response (CR/PR) to ibrutinib; “stable disease (SD)”; and “primary progressors (PP)”—patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23–7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03–8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17–37.62, p
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- 2022
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6. Pulmonary Haemosiderosis Secondary to Hereditary Haemochromatosis; a Case Report
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Waqas Jehangir, Alexander Karabachev, and Elvira Umyarova
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Dyspnoea ,ferritins ,haemochromatosis protein ,haemochromatosis ,haemosiderosis ,mutation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Hereditary haemochromatosis (HH) is an autosomal recessive disease of increased intestinal absorption of iron, leading to accumulation in tissues which may progress to organ damage, most commonly in the liver. Iron deposition in the liver can lead to cirrhosis and hepatocellular carcinoma. Other common manifestations of haemochromatosis include diabetes, bronzing of the skin, arthropathy and cardiomyopathy. Here, we describe a case of pulmonary haemosiderosis secondary to HH. Case Description: A 49-year-old male with no medical history or family history of iron overload presented with fatigue, shortness of breath and chest pain after a recent finding of elevated ferritin. The patient was found to have biallelic C282Y mutations of the human homeostatic iron regulator protein (HFE) protein and after further workup with laboratory tests and imaging was diagnosed with HH with secondary pulmonary haemosiderosis. The patient is receiving twice weekly phlebotomies and has had an overall improvement in his symptoms. Practical Implications: The presentation of haemochromatosis can vary widely depending on the severity of iron overload and the presence of conditions that predispose organ dysfunction. Pulmonary haemosiderosis is a very rare manifestation of HH. This report illustrates the various manifestations of this disease and provides insight into this rare presentation to improve the diagnosis of this disease.
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- 2020
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7. Myelodysplastic Syndrome with Transfusion Dependence Treated with Venetoclax
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Waqas Jehangir, Alexander Karabachev, Taimoor Jahangir, and Elvira Umyarova
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Myelodysplastic syndromes are characterized by ineffective hematopoiesis in one or more lineages of the bone marrow. They are a group of heterogeneous clonal stem cell malignancies with a high risk to progress to acute myeloid leukemia. Currently, there are no curative FDA-approved medications for myelodysplastic syndromes. Hematopoietic cell transplantation is potentially the only curative option; however, treatment is often unavailable due to age and comorbidities. Hypomethylating agents, azacitidine and decitabine, and the immunomodulatory agent, lenalidomide, are the only FDA approved medications for the treatment of MDS, all of which are noncurative. Venetoclax, an inhibitor of the antiapoptotic protein BCL-2 used to treat chronic lymphocytic leukemia, is currently being evaluated in clinical trials as a monotherapy in high-risk myelodysplastic syndromes/acute myeloid leukemia. We present a patient with transfusion-dependent myelodysplastic syndromes refractory to the current standard of care treatment not a candidate for hematopoietic cell transplantation who responded well to monotherapy treatment with venetoclax and has since remained transfusion-independent.
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- 2020
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8. A Rare Manifestation of a Rare Disease: Mantle Cell Lymphoma Presenting With Aseptic Meningitis
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Elvira Umyarova MD, Sreedhar Adapa MD, Srikanth Naramala MD, Vijay Gayam MD, Narothama Reddy Aeddula MD, and Venu Madhav Konala MD
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Medicine (General) ,R5-920 ,Pathology ,RB1-214 - Abstract
Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma characterized by clonal proliferation of follicular mantle zone B lymphocytes. It is caused by abnormal chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. This leads to activation of anti-apoptotic pathways and abnormal proliferation of MCL cells. Patients can present with an indolent course or a fulminant disease with short overall survival. The disease frequently involves extranodal organs, but rarely manifests with neurological symptoms. We report a rare case of aberrant CD5-negative MCL presenting with aseptic meningitis.
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- 2019
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9. A complex acid-base disorder in an alcoholic
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Elvira Umyarova and Natasha Suvorava
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high anion gap metabolic acidosis ,alcoholic ketoacidosis ,chronic alcohol abuse. ,Diseases of the respiratory system ,RC705-779 - Published
- 2014
10. Factors affecting mortality in patients with COPD exacerbations requiring ICU admission
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Chok Limsuwat, Nopakoon Nantsupawat, Elvira Umyarova, Kamonpun Ussavarungsi, and Kenneth Nugent
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COPD ,mortality ,acute flare ,risk factors ,Diseases of the respiratory system ,RC705-779 - Abstract
Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often require hospital admission and have a significant mortality rate. Patients with AECOPD who need intensive care (ICU) have higher mortality rates. Identifying factors associated with increased mortality might change approaches to treatment and improve communication with patients’ families about prognosis. Methods: Patients with AECOPD (ICD 9 code 491.21) directly admitted to the ICU between 1/1/2006 and 12/31/2010 were retrospectively reviewed. The inclusion criteria were age 45 years or older, diagnosis of AECOPD, and admission to an ICU. The exclusion criteria included any history of another respiratory disease or decompensated cardiac disease. The primary goal was to determine factors which affect survival. Result: Two hundred and seventeen patients were included this study. The mean ages were 70.4±10.4 years in the in-hospital death group and 66.4±10.9 years in the survivors. The overall mortality rate was 12%. Multivariate analysis showed that the mortality rate was significantly associated with a low mean arterial blood pressure (MAP) (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.86-0.96), an intubation event (OR 6.12, 95% CI 1.24-30.87), and an elevated blood urea nitrogen (BUN) (OR 1.06, 95% CI 1.01-1.12) (p
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- 2013
11. Survival outcomes following autologous stem cell transplant with melphalan 140mg/m2 versus 200mg/m2 preparative regimens in patients with multiple myeloma
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Nidhi Sharma, Evan Benson, Qiuhong Zhao, Jordan Nunnelee, Francesca Cottini, Patrick Elder, Ashley Rosko, Naresh Bumma, Abdullah Khan, Elvira Umyarova, Srinivas Devarakonda, Yvonne A. Efebera, and Don M. Benson
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Cancer Research ,Oncology ,Hematology - Published
- 2023
12. Impact of Monoclonal Protein at Diagnosis on Outcomes in Patients with Marginal Zone Lymphoma: A Multicenter Cohort Study
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Narendranath Epperla, Qiuhong Zhao, Lauren Shea, Reem Karmali, Pallawi Torka, Timothy Seijung Oh, Andrea Anampa-Guzman, Ximena Jordan Bruno, Elvira Umyarova, Kathryn Lindsey, Irl Brian Greenwell, Sayan Mullick Chowdhury, Yazeed Sawalha, Beth Christian, Natalie S. Grover, Nancy L. Bartlett, and Adam J. Olszewski
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
13. Outcomes After Salvage Autologous Hematopoietic Cell Transplant for Patients With Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience
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Abdullah M. Khan, Michael Ozga, Harshil Bhatt, Muhammad S. Faisal, Sadia Ansari, Qiuhong Zhao, Naresh Bumma, Francesca Cottini, Srinivas Devarakonda, Ashley Rosko, Nidhi Sharma, Elvira Umyarova, and Don Benson
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Cancer Research ,Oncology ,Hematology - Abstract
The role of salvage autologous hematopoietic cell transplantation (sAHCT2) for patients with relapsed/refractory multiple myeloma (RRMM) in the era of modern therapeutics is unclear. As prospective data is limited, we conducted a retrospective analysis to determine the outcomes of sAHCT2.We conducted a single-institution, retrospective analysis of patients who received sAHCT2 at The Ohio State University from 2000 to 2018. Patients who received a second transplant as part of a planned tandem or autologous-allogeneic transplant were excluded.Fifty-seven patients were treated with sAHCT2. Patients had a median of 2 lines of therapy after AHCT1 prior to their sAHCT2; 70% had prior immunomodulatory imide drugs, 82% had prior proteasome inhibitor, and 20% had prior anti-CD38 monoclonal antibodies as part of re-induction therapy. Forty-two percent of patients attained ≥VGPR prior to sAHCT2. Seventy-four were treated with melphalan 200 mg/mFor MM patients deriving durable remission after their AHCT1, sAHCT2 was safe and resulted in deep and durable remissions.
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- 2022
14. Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis with Kidney Involvement in a Patient with AL Amyloidosis
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Richard Solomon, Elvira Umyarova, Pamela C. Gibson, Brendan L. Thoms, and Varun Agrawal
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Vasculitis ,Pathology ,medicine.medical_specialty ,Single Case ,urologic and male genital diseases ,Glomerulonephritis ,immune system diseases ,medicine ,AL amyloidosis ,ANCA-related nephritis and vasculitis ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Autoantibody ,Acute kidney injury ,medicine.disease ,Diseases of the genitourinary system. Urology ,Amyloid AA and AL ,Nephrology ,Renal biopsy ,RC870-923 ,business ,Kidney disease - Abstract
Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis has occasionally been associated with other systemic glomerulonephritis, such as anti-glomerular basement membrane disease. Here, we report the first clinical case of ANCA-associated crescentic glomerulonephritis with AL amyloidosis. An 81-years-old gentleman presented to the hospital with acute kidney injury (serum creatinine 4.7 mg/dL) on a background of chronic kidney disease and volume overload. Autoimmune serology was remarkable for p-ANCA and myeloperoxidase positivity. A renal biopsy confirmed pauci-immune glomerulonephritis and lambda light-chain amyloid deposition (confirmed on liquid chromatography and tandem mass spectrometry). The patient was initially managed with rituximab and subsequently transitioned to bortezomib-based chemotherapy but died due to decompensated heart failure. This case report promotes greater awareness of the unusual presentation of amyloidosis and guides future research and treatment.
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- 2021
15. The Co-Occurrence of 1q21+/1q23+ and t(4;14) Abnormalities with Specific Clone Size Is Predictive of Shorter Response to Transplant in Patients with Multiple Myeloma
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Michael P. Ozga, Qiuhong Zhao, Naresh Bumma, Ashley E. Rosko, Abdullah Khan, Srinivas Devarakonda, Elvira Umyarova, Don M. Benson, and Francesca Cottini
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
16. T-Cell Senescence and Exhaustion Are Associated with Interval Progression of Multiple Myeloma before Autologous Hematopoietic Cell Transplant
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Alicia Bao, Ruchi Kudalkar, Jose Rodriguez, Qiuhong Zhao, Nidhi Sharma, Naresh Bumma, Srinivas Devarakonda, Abdullah Khan, Ashley E. Rosko, Elvira Umyarova, Don M. Benson, and Francesca Cottini
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
17. Comparison of Patient Outcomes With Two Different Formulations of Melphalan as Conditioning Chemotherapy for Autologous Hematopoietic Cell Transplantation in Multiple Myeloma
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Abdullah M. Khan, Filiz Yucebay, Qiuhong Zhao, Elvira Umyarova, Francesca Cottini, Naresh Bumma, Ashley Rosko, Don Benson, Nidhi Sharma, Yvonne Efebera, and Srinivas Devarakonda
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Cancer Research ,Oncology ,Hematology - Abstract
High-dose melphalan (HDM) with autologous hematopoietic cell transplantation (AHCT) after induction chemotherapy is considered standard of care in transplant-eligible patients with newly-diagnosed multiple myeloma (MM). Alkeran melphalan has propylene glycol as a solvent (PG-mel) while Evomela utilizes a propylene glyclol-free formulation (PGF-mel). We evaluated the differences in efficacy and safety of the 2 formulations as there are no prospective head-to-head trials.We retrospectively reviewed the medical records of all 259 consecutive MM patients who received PGF-mel as part of HDM-AHCT at The Ohio State University (OSU). The comparator group was the preceding 255 patients who received PG-mel.Baseline patient characteristics were similar between the 2 groups. Post-AHCT rates of relapse were comparable in the PG-mel and PGF-mel groups. Some adverse events were observed at a higher frequency in the PG-mel group compared to the PGF-mel group (grade ≥ 2 mucositis, febrile neutropenia, other infectious complications, and acute renal insufficiency). Time to neutrophil engraftment was slightly longer in the PG-mel group while time to platelet engraftment was longer in PGF-mel group. Red cell transfusion requirement was higher with the use of PG-mel but not platelet transfusion. Duration of hospitalization was slightly shorter with PGF-mel but readmission rates within 30 days of discharge were higher.Considering possible confounding factors could possibly account for observed differences in some adverse events, the comparable treatment responses, and difference in cost of the 2 formulation, The OSU reverted to PG-mel as the preferred formulation for HDM-AHCT in MM.
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- 2022
18. P-250: Predictive factors for outcomes after salvage autologous hematopoietic cell transplant for patients with relapsed/refractory multiple myeloma: a single-institution experience
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Abdullah Khan, Muhammad Faisal, Qiuhong Zhao, Michael Ozga, Naresh Bumma, Francesca Cottini, Srinivas Devarakonda, Ashley Rosko, Elvira Umyarova, and Don Benson
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Cancer Research ,Oncology ,Hematology - Published
- 2022
19. Treatment outcomes of triple class refractory multiple myeloma: a benchmark for new therapies
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Saad Z. Usmani, Natalie S. Callander, Elvira Umyarova, Parameswaran Hari, Shaji Kumar, Ehsan Malek, Susan Bal, Saurabh Chhabra, Michaela Liedtke, Robert F. Cornell, Ankit Kansagra, Smith Giri, Luciano J. Costa, Yubin Kang, Kelly N. Godby, and Ravi Vij
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Treatment outcome ,MEDLINE ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,Refractory Multiple Myeloma ,Hematology ,Middle Aged ,Class (biology) ,Progression-Free Survival ,Benchmarking ,Treatment Outcome ,Benchmark (computing) ,Female ,business ,Multiple Myeloma - Published
- 2021
20. SURVIVAL FOLLOWING FIRST RELAPSE IN YOUNGER PATIENTS WITH MANTLE CELL LYMPHOMA
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Alexandra M. Donovan, Narendranath Epperla, Elizabeth Handorf, Frederick Lansigan, Jason B. Kaplan, Michael C. Churnetski, Kami J. Maddocks, Elvira Umyarova, J. K. Anderson, Andrew M. Evens, Catherine Diefenbach, David A. Bond, Mengjun Wang, Jonathan Cohen, Julie M. Vose, Marcus Messmer, Alexandra E. Kovach, S. Narayana Rao Gari, N.M. Reddy, Alina S. Gerrie, Veronika Bachanova, Andreas K. Klein, Reem Karmali, Martin Bast, Julio C. Chavez, Brian T. Hill, Timothy S. Fenske, Oscar Calzada, Kay M. Ristow, David J. Inwards, P. B. Caimi, Diego Villa, Shalin Kothari, Yazeed Sawalha, Jennifer E Amengual, Martha Glenn, Shaoying Li, Stefan K. Barta, Jennifer K. Lue, Amitkumar Mehta, James N. Gerson, N. Wagner-Johntson, J. Mederios, Francisco J. Hernandez-Ilizaliturri, Saurabh Rajguru, Bhaskar Kolla, Bijal D. Shah, and Daniel J. Landsburg
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Oncology ,Cancer Research ,medicine.medical_specialty ,First relapse ,business.industry ,Internal medicine ,medicine ,Mantle cell lymphoma ,Hematology ,General Medicine ,medicine.disease ,business - Published
- 2021
21. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy
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Michaela Liedtke, Amarendra K. Neppalli, Elizabeth McGehee, Ehsan Malek, Saad Z. Usmani, Robert F. Cornell, Swapna Narayana, Ankit Kansagra, Natalie S. Callander, Elvira Umyarova, Parameswaran Hari, Arjun Lakshman, Ridhi Gupta, Barry Paul, Joshua Mansour, Zhubin Gahvari, Ujjawal H. Gandhi, William Varnado, Alyssa Barnstead, Saurabh Chhabra, Mark A. Fiala, Emma C. Scott, Megan Jagosky, Saranya Kodali, Ravi Vij, Yubin Kang, Kelly N. Godby, Luciano J. Costa, and Shaji Kumar
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Population ,Antibodies, Monoclonal, Humanized ,Article ,Cohort Studies ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Refractory ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Immunologic Factors ,Progression-free survival ,education ,Multiple myeloma ,Aged ,Aged, 80 and over ,Isatuximab ,education.field_of_study ,Membrane Glycoproteins ,business.industry ,Antibodies, Monoclonal ,Daratumumab ,Hematology ,Middle Aged ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Carfilzomib ,Progression-Free Survival ,Regimen ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Female ,Immunotherapy ,Multiple Myeloma ,business ,Proteasome Inhibitors - Abstract
The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T(0)) was 50.1 months. The median overall survival (OS) from T(0) for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T(0) in 249 (90%) patients. Overall response rate to first regimen after T(0) was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.
- Published
- 2019
22. Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era
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Kami J. Maddocks, Oscar Calzada, Brian T. Hill, Timothy F. Burns, Michael I. Wang, Julie M. Vose, Alexandra E. Kovach, Bhaskar Kolla, Andreas K. Klein, Bhargavi Pulluri, Alexandra M. Donovan, Frederick Lansigan, David J. Inwards, Jennifer K. Lue, Elizabeth Handorf, Martin Bast, Paolo Caimi, Jonathon B. Cohen, Jason B. Kaplan, Richard I. Fisher, Michael C. Churnetski, Timothy S. Fenske, Elvira Umyarova, Diego Villa, Parv Chapani, Veronika Bachanova, Yazeed Sawalha, David A. Bond, Julio C. Chavez, Martha Glenn, Shaoying Li, Marcus Messmer, Shalin Kothari, Alina S. Gerrie, Stefan K. Barta, L. Jeffrey Medeiros, Reem Karmali, Jennifer E Amengual, Amitkumar Mehta, Saurabh Rajguru, Nishitha Reddy, Andrew M. Evens, Swapna Narayana Rao Gari, Catherine Diefenbach, Nina D. Wagner-Johnston, James N. Gerson, Jennifer Kelly Anderson, Francisco J. Hernandez-Ilizaliturri, Bijal D. Shah, and Daniel J. Landsburg
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Lymphoma, Mantle-Cell ,Risk Assessment ,Transplantation, Autologous ,Young Adult ,Antineoplastic Agents, Immunological ,Cyclin D1 ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Young adult ,Aged ,Retrospective Studies ,business.industry ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Induction chemotherapy ,ORIGINAL REPORTS ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Lymphoma ,Transplantation ,North America ,Female ,Rituximab ,Mantle cell lymphoma ,business ,medicine.drug - Abstract
PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.
- Published
- 2019
23. P-201: Triple-class refractory disease as a modern therapeutic benchmark for clinical trials testing new agents for relapsed refractory Multiple Myeloma
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Ravi Vij, Shaji Kumar, Smith Giri, Saad Z. Usmani, Robert F. Cornell, Ankit Kansagra, Michaela Liedtke, Saurabh Chhabra, Luciano J. Costa, Yubin Kang, Kelly N. Godby, Susan Bal, Ehsan Malek, Natalie S. Callander, Elvira Umyarova, and Parameswaran Hari
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Oncology ,Cancer Research ,Class (computer programming) ,medicine.medical_specialty ,business.industry ,Refractory Disease ,Hematology ,medicine.disease ,Clinical trial ,Internal medicine ,Relapsed refractory ,Benchmark (computing) ,Medicine ,business ,Multiple myeloma - Published
- 2021
24. Overall survival of patients with triple‐class refractory multiple myeloma treated with selinexor plus dexamethasone vs standard of care in <scp>MAMMOTH</scp>
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Amarendra K. Neppalli, Sagar Lonial, Shaji Kumar, Sundar Jagannath, Jatin P. Shah, Mark A. Fiala, Paul G. Richardson, Joshua Mansour, Megan Jagosky, Ujjawal H. Gandhi, Zhubin Gahvari, Yubin Kang, Kelly N. Godby, Michaela Liedtke, Elizabeth McGehee, Ravi Vij, Xiwen Ma, David S. Siegel, Robert F. Cornell, Barry Paul, Ehsan Malek, William Varnado, Ankit Kansagra, Shijie Tang, Luciano J. Costa, Saad Z. Usmani, Emma C. Scott, Arjun Lakshman, Michael Kauffman, Noa Biran, Ridhi Gupta, Saurabh Chhabra, Saranya Kodali, Natalie S. Callander, Elvira Umyarova, Parameswaran Hari, Sharon Shacham, and Ajai Chari
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Oncology ,Disease free survival ,medicine.medical_specialty ,Standard of care ,business.industry ,Refractory Multiple Myeloma ,Hematology ,Clinical trial ,Multicenter study ,Internal medicine ,medicine ,Overall survival ,business ,Survival rate ,Dexamethasone ,medicine.drug - Published
- 2020
25. Caplacizumab treatment for acquired refractory thrombotic thrombocytopenic purpura
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Kara K. Landry, Sundas Khan, and Elvira Umyarova
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medicine.medical_specialty ,Refractory ,business.industry ,medicine ,Thrombotic thrombocytopenic purpura ,Hematology ,Caplacizumab ,business ,medicine.disease ,Dermatology - Published
- 2020
26. Myelodysplastic Syndrome with Transfusion Dependence Treated with Venetoclax
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Alexander Karabachev, Elvira Umyarova, Taimoor Jahangir, and Waqas Jehangir
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Azacitidine ,Decitabine ,Case Report ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Diseases of the blood and blood-forming organs ,Lenalidomide ,Venetoclax ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,General Medicine ,medicine.disease ,Transplantation ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,RC633-647.5 ,business ,medicine.drug - Abstract
Myelodysplastic syndromes are characterized by ineffective hematopoiesis in one or more lineages of the bone marrow. They are a group of heterogeneous clonal stem cell malignancies with a high risk to progress to acute myeloid leukemia. Currently, there are no curative FDA-approved medications for myelodysplastic syndromes. Hematopoietic cell transplantation is potentially the only curative option; however, treatment is often unavailable due to age and comorbidities. Hypomethylating agents, azacitidine and decitabine, and the immunomodulatory agent, lenalidomide, are the only FDA approved medications for the treatment of MDS, all of which are noncurative. Venetoclax, an inhibitor of the antiapoptotic protein BCL-2 used to treat chronic lymphocytic leukemia, is currently being evaluated in clinical trials as a monotherapy in high-risk myelodysplastic syndromes/acute myeloid leukemia. We present a patient with transfusion-dependent myelodysplastic syndromes refractory to the current standard of care treatment not a candidate for hematopoietic cell transplantation who responded well to monotherapy treatment with venetoclax and has since remained transfusion-independent.
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- 2020
27. Pulmonary Haemosiderosis Secondary to Hereditary Haemochromatosis; a Case Report
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Alexander Karabachev, Elvira Umyarova, and Waqas Jehangir
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ferritins ,Pathology ,medicine.medical_specialty ,Hereditary haemochromatosis ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,haemochromatosis protein ,Pulmonary haemosiderosis ,haemochromatosis ,Dyspnoea ,Medicine ,haemosiderosis ,mutation ,business ,RC254-282 - Abstract
Introduction: Hereditary haemochromatosis (HH) is an autosomal recessive disease of increased intestinal absorption of iron, leading to accumulation in tissues which may progress to organ damage, most commonly in the liver. Iron deposition in the liver can lead to cirrhosis and hepatocellular carcinoma. Other common manifestations of haemochromatosis include diabetes, bronzing of the skin, arthropathy and cardiomyopathy. Here, we describe a case of pulmonary haemosiderosis secondary to HH. Case Description: A 49-year-old male with no medical history or family history of iron overload presented with fatigue, shortness of breath and chest pain after a recent finding of elevated ferritin. The patient was found to have biallelic C282Y mutations of the human homeostatic iron regulator protein (HFE) protein and after further workup with laboratory tests and imaging was diagnosed with HH with secondary pulmonary haemosiderosis. The patient is receiving twice weekly phlebotomies and has had an overall improvement in his symptoms. Practical Implications: The presentation of haemochromatosis can vary widely depending on the severity of iron overload and the presence of conditions that predispose organ dysfunction. Pulmonary haemosiderosis is a very rare manifestation of HH. This report illustrates the various manifestations of this disease and provides insight into this rare presentation to improve the diagnosis of this disease.
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- 2020
28. Predictive Factors and Outcomes for Ibrutinib Therapy in Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study
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Cherie Tan, Lauren Shea, Yazeed Sawalha, Farrukh T. Awan, Geoffrey Shouse, Beth Christian, Tamara K. Moyo, Jonathon B. Cohen, Paolo Caimi, Qiuhong Zhao, Nishitha Reddy, Andrew R. Hsu, Murali Janakiram, Adam J. Olszewski, Joseph Maakaron, Natalie S Grover, Neil Palmisiano, Stefan K. Barta, Elvira Umyarova, Praveen Ramakrishnan Geethakumari, Kathryn G. Lindsey, Pallawi Torka, Alex F. Herrera, Kevin A. David, Celeste M. Bello, David M. Weiner, Ximena Jordan-Bruno, Narendranath Epperla, Nancy L. Bartlett, Michael C. Churnetski, Malathi Kandarpa, Sayan Mullick Chowdhury, Irl Brian Greenwell, Julia Sheets, Colin Thomas, and Ryan A. Wilcox
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Marginal zone lymphoma ,Cell Biology ,Hematology ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Ibrutinib ,Internal medicine ,Relapsed refractory ,Medicine ,business ,health care economics and organizations ,Cohort study - Abstract
Introduction Ibrutinib was FDA approved for relapsed or refractory (R/R) marginal zone lymphoma (MZL) based on a phase II clinical trial that showed an overall response rate of 48% (Noy et al, Blood 2017). However, factors associated with response to ibrutinib in R/R MZL and outcomes of patients after progression on ibrutinib are unknown. Given the poor survival in other B-cell lymphomas such as mantle cell lymphoma (MCL) after progression on ibrutinib (Martin P et al, Blood 2016), we sought to evaluate clinicopathologic characteristics predictive of ibrutinib failure in R/R MZL, and describe outcomes of patients who experienced progression on ibrutinib therapy. Methods We performed a multicenter retrospective study of MZL patients treated at 19 US medical centers. Eligible patients were ≥ 18 years diagnosed with MZL from 2010-2019, who received ibrutinib for R/R MZL. Patients achieving a complete response (CR) or partial response (PR) with ibrutinib were considered ibrutinib responders, while those who had stable disease (SD) or progression of disease (PD) were classified as non-responders. The primary endpoint was to evaluate factors predictive of primary progression (PD) on ibrutinib. Secondary endpoints include evaluation of predictors of overall survival (OS) and progression-free survival (PFS) following ibrutinib therapy, assessment of outcomes based on the sequencing of ibrutinib therapy, and evaluation of outcomes following ibrutinib failure. PFS was defined as time from the start of ibrutinib therapy until lymphoma relapse/progression or death from any cause, censoring at last clinical assessment if no progression or death. OS was defined as time from the start of ibrutinib treatment until death or last follow-up. A multivariable Poisson regression analysis was performed to model ibrutinib progression on the clinicopathologic factors (see Table). To identify significant predictors for OS and PFS, we used a multivariable Cox model. Results 101 patients with R/R MZL received ibrutinib, of whom 99 had sufficient data for inclusion in the analysis. Among these patients, 63% (n=62) had CR/PR to ibrutinib (ibrutinib responders, CR=17, PR=45) and 37% (n=37) had no response (ibrutinib non-responders, SD=25, PD=12). The median duration of follow-up was 1.8 years (range=0.1-5.4 years) and 2 years (range=0.2-6.3 years) for ibrutinib responders and non-responders, respectively. Baseline characteristics of the R/R MZL patients stratified by ibrutinib response are shown in the Table. Among all the baseline factors examined for association with ibrutinib progression, only primary refractory disease (refractory to frontline therapy, RR=3.78, 95%CI=1.36-10.45, p=0.01) was predictive of a higher probability of primary progression on ibrutinib on multivariable analysis. The median OS was significantly better for responders (NR [not reached], 95%CI=3.2-NR) compared to non-responders (3.4 years, 95%CI=1.4-NR) (Figure 1A). Achieving CR/PR with ibrutinib (HR=0.22, 95%CI=0.09-0.52) and lack of complex cytogenetics (HR=0.22, 95%CI=0.08-0.59) were predictors of superior PFS. Similarly, ibrutinib response (HR=0.13, 95%CI=0.03-0.53) and lack of complex cytogenetics (HR=0.19, 95%CI=0.04-0.87) were predictors of better OS. There was no difference in PFS or OS based on the timing of ibrutinib administration (second vs third vs fourth line and beyond, Figure 1B and 1C). The median post ibrutinib relapse/progression OS (PROS) for patients who initially responded then progressed on ibrutinib (secondary progression, n=19) was 4 years (Figure 1D). The median PROS for patients who had no response to ibrutinib were stratified according to SD vs PD. The median PROS for those who had SD was NR and those with PD was 0.1 year (Figure 1E). Conclusion This is the largest series of R/R MZL patients treated with ibrutinib. A history of primary refractory disease was predictive of primary progression on ibrutinib, while the presence of complex cytogenetics was associated with inferior PFS and OS. In contrast to MCL, the outcomes of patients who progress on ibrutinib in R/R MZL are not poor except for the primary progression cohort (those with PD as the best response to ibrutinib). Improving therapeutic options for patients who experience PD with ibrutinib treatment represents an urgent unmet need and these patients should be prioritized for evaluation of novel therapeutic approaches. Figure Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Reddy:Genentech, BMS: Research Funding; KITE Pharma, Abbvie, BMS, Celgene: Consultancy. Caimi:Genentech: Research Funding; Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding. Greenwell:Lymphoma Research Foundation: Research Funding; Acrotech Biopharma LLC, Kyowa Kirin: Consultancy. Janakiram:Takeda, Fate, Nektar: Research Funding. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Awan:Genentech: Consultancy; Janssen: Consultancy; Astrazeneca: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Dava Oncology: Consultancy; Celgene: Consultancy; Blueprint medicines: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy. Barta:Monsanto: Consultancy; Atara: Honoraria; Seattle Genetics: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria. Grover:Genentech: Research Funding; Tessa: Consultancy. Bartlett:Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed Therapeutics: Research Funding; Acerta: Consultancy; BTG: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Merck: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding; BMS/Celgene: Research Funding. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Herrera:Pharmacyclics: Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Karyopharm: Consultancy.
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- 2020
29. C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional 'hits' and outcomes with subsequent therapy
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Michael Jaglal, Nishitha Reddy, Luciano J. Costa, Narendranath Epperla, Jonathon B. Cohen, Mehdi Hamadani, Cristiana A Costa, Elvira Umyarova, Andrew J. Evans, Frederick Lansigan, Nasheed Hossain, Martha Glenn, Veronika Bachanova, Stefan K. Barta, Mohammed Salhab, Ana C. Xavier, Zheng Zhou, Francisco J. Hernandez-Ilizaliturri, Saurabh Chhabra, Reem Karmali, Christopher R. Flowers, Amitkumar Mehta, Julio C. Chavez, Kami J. Maddocks, Timothy S. Fenske, Zeina Al-Mansour, and Oscar Calzada
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hazard ratio ,Salvage therapy ,Cancer ,Retrospective cohort study ,medicine.disease ,Lymphoma ,Surgery ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Chemoimmunotherapy ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,business ,030215 immunology - Abstract
BACKGROUND The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in
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- 2017
30. A Rare Manifestation of a Rare Disease: Mantle Cell Lymphoma Presenting With Aseptic Meningitis
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Vijay Gayam, Narothama Reddy Aeddula, Venu Madhav Konala, Srikanth Naramala, Sreedhar Adapa, and Elvira Umyarova
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Pancytopenia ,Epidemiology ,Fulminant ,mantle cell lymphoma ,Case Report ,Chromosomal translocation ,Lymphoma, Mantle-Cell ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Cyclin D1 ,Bone Marrow ,immune system diseases ,hemic and lymphatic diseases ,medicine ,lcsh:Pathology ,Humans ,Meningitis, Aseptic ,Safety, Risk, Reliability and Quality ,Cerebrospinal Fluid ,030304 developmental biology ,0303 health sciences ,lcsh:R5-920 ,business.industry ,Mantle zone ,MIPI ,Aseptic meningitis ,Antigens, CD20 ,medicine.disease ,Immunohistochemistry ,Lymphoma ,aseptic meningitis ,030220 oncology & carcinogenesis ,Mantle cell lymphoma ,business ,lcsh:Medicine (General) ,Safety Research ,Rare disease ,lcsh:RB1-214 - Abstract
Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma characterized by clonal proliferation of follicular mantle zone B lymphocytes. It is caused by abnormal chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. This leads to activation of anti-apoptotic pathways and abnormal proliferation of MCL cells. Patients can present with an indolent course or a fulminant disease with short overall survival. The disease frequently involves extranodal organs, but rarely manifests with neurological symptoms. We report a rare case of aberrant CD5-negative MCL presenting with aseptic meningitis.
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- 2019
31. Overall Survival of Triple Class Refractory, Penta-Exposed Multiple Myeloma (MM) Patients Treated with Selinexor Plus Dexamethasone or Conventional Care: A Combined Analysis of the STORM and Mammoth Studies
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Mark A. Fiala, Saad Z. Usmani, Jatin J. Shah, Sundar Jagannath, Sagar Lonial, Shijie Tang, Saurabh Chhabra, Yubin Kang, Kelly N. Godby, Luciano J. Costa, Shaji Kumar, Arjun Lakshman, Robert F. Cornell, Paul G. Richardson, Noa Biran, Ehsan Malek, Ajai Chari, David S. Siegel, Michael Kauffman, Xiwen Ma, Amarendra K. Neppalli, Ujjawal H. Gandhi, Sharon Shacham, Natalie S. Callander, Elvira Umyarova, and Parameswaran Hari
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Oncology ,medicine.medical_specialty ,Bortezomib ,business.industry ,Immunology ,Daratumumab ,Cell Biology ,Hematology ,Pomalidomide ,medicine.disease ,Biochemistry ,Carfilzomib ,chemistry.chemical_compound ,Refractory ,chemistry ,Internal medicine ,medicine ,business ,Dexamethasone ,Multiple myeloma ,medicine.drug ,Lenalidomide - Abstract
Introduction: Proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and the CD38 monoclonal antibody daratumumab (dara) have transformed the management of MM, yet eventual refractoriness to these agents seems inevitable. Relapsed and refractory MM (RRMM) which becomes triple class refractory (TCR, i.e. refractory to a PI, an IMiD and Dara) uncommonly responds to further lines of therapy and survival is dismal. Selinexor is a selective inhibitor of nuclear export compound targeting exportin 1 (XPO1) which is overexpressed in MM cells and essential for their survival. In the STORM study, selinexor in combination with low-dose dexamethasone (Sd) demonstrated promising efficacy in TCR, penta-exposed (TCR-PE, i.e. exposed to lenalidomide, pomalidomide, bortezomib, carfilzomib and dara) MM. Establishing the natural history for outcomes in the TCR-PE population can help provide context to understand the outcomes observed with Sd in STORM. In the retrospective MAMMOTH study, we reported the outcomes of patients with RRMM after they became refractory to dara, including a subset of patients who were TCR. We further analyzed the MAMMOTH dataset to generate a cohort of patients similar to patients in STORM in order to compare conventional care vs. Sd. Methods: We included all patients in STORM who received Sd as the first line therapy after they achieved TCR-PE status (n=64). We extracted from the MAMMOTH dataset all patients who were not exposed to Sd in a subsequent line of therapy, became TCR-PE and who received subsequent MM-directed therapy (n=128). Overall response rate (ORR) was evaluated according to IMWG criteria. Overall survival (OS) was calculated from the time of initiation of next line of therapy after TCR-PE status until death or last follow-up. We compared OS in STORM vs. MAMMOTH utilizing cox-regression analysis with adjustment for covariables potentially influencing the outcome. Results: Baseline patient characteristics and prior therapies are per table. The two cohorts were similar in terms of age, number of prior lines of therapy and presence of high-risk cytogenetic abnormalities. STORM patients had longer time between MM diagnosis and post TCR-PE therapy with a higher proportion of refractoriness to carfilzomib. Patients in STORM had ORR to Sd of 32.8% vs 25.0% for patients receiving conventional care in MAMMOTH (P=0.078). In direct comparison, patients in STORM had better OS than patients in MAMMOTH (median 10.4 vs. 6.9 months) (P=0.043, figure). In multivariate analysis, STORM patients had lower risk of death in comparison with MAMMOTH patients (aHR=0.55, 95%C.I. 0.35-0.86, P=0.009). Refractoriness to carfilzomib (aHR=2.20, 95%C.I. 1.16-4.15, P=0.015) and high-risk cytogenetics (aHR-1.66, 95% C.I. 1.13-2.42, P=0.009) were also associated with inferior OS. Conclusion: Despite inherent limitations in comparison of trial enrollees vs. real world patients, this analysis suggests improved OS with Sd vs conventional care in patients with TCR-PE RRMM. Prognosis for these patients remains poor and underscores the need for therapeutic advancements. Disclosures Costa: Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Hari:Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria. Kumar:Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. Tang:Karyopharm: Employment. Shah:Karyopharm Therapeutics Inc: Employment, Equity Ownership. Jagannath:BMS: Consultancy; Merck: Consultancy; Medicom: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy; Multiple Myeloma Research Foundation: Speakers Bureau. Chari:Oncoceutics: Research Funding; Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding. Shacham:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Ma:Karyopharm: Employment, Equity Ownership. Siegel:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Biran:Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol Meyers Squibb: Research Funding. Lonial:BMS: Consultancy; Genentech: Consultancy; GSK: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Celgene Corporation: Consultancy, Research Funding; Karyopharm: Consultancy. Richardson:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Kauffman:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Malek:Adaptive: Consultancy; Amgen: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Medpacto: Research Funding. Fiala:Incyte: Research Funding. Usmani:Amgen, Celgene, Janssen, Sanofi, Takeda: Speakers Bureau; Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, SkylineDX, Takeda: Other: Consultant/Advisor; Amgen Array Biopharma, Bristol-Myers Squibb, Celgene, Janssen, Merck, Pharmacyclics, Sanofi, Takeda: Other: Research Grant. Kang:Takeda Oncology: Consultancy; InCyte Corportation: Research Funding. Cornell:Takeda: Consultancy; KaryoPharm: Consultancy.
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- 2019
32. Outcomes of Patients with Refractory Peripheral T-Cell Lymphoma, Angioimmunoblastic and Other Nodal Lymphomas of T Follicular Helper-Cell Origin (OPerA)
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Suchitra Sundaram, Jonathan E. Brammer, Adam Zayac, Elvira Umyarova, Paolo Caimi, Waqas Jehangir, Nilanjan Ghosh, Stefan K. Barta, Sheenu Sheela, Adam J. Olszewski, Zachary Braunstein, Sunita D. Nasta, and Joanna Rhodes
- Subjects
business.industry ,medicine.medical_treatment ,Immunology ,Cell ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Lymphoma ,Romidepsin ,Transplantation ,medicine.anatomical_structure ,medicine ,Cancer research ,T-cell lymphoma ,Bone marrow ,business ,NODAL ,medicine.drug - Abstract
Introduction: T cell lymphomas are heterogenous with an overall poor prognosis. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T cell lymphoma (AITL) are the two most common subtypes in the US accounting for 45% of diagnoses. Based on overlapping recurrent molecular and cytogenetic abnormalities, the WHO created an umbrella category of nodal T-cell lymphomas with T-follicular helper phenotype (TFH lymphoma), which includes AITL and PTCL with TFH phenotype (Swerdlow SH, et al. Blood. 2016). 25-30% of patients (pts) are refractory to initial therapy and even amongst responders to initial therapy, relapse is common. Survival after relapse or progression (R/P) is typically measured only in months. Outcomes have not changed significantly even with the introduction of several new agents in the last 10 years (Chihara D, et al. Br J Haematol. 2017). There remains no standard 2nd line therapy or guidance on sequencing of therapies as interpretation of clinical data in T-cell lymphoma is frequently hampered by the heterogeneity of the patient population and small sample size. The aim of our study was to determine outcomes in a large, well-defined group of pts with either primary refractory PTCL-NOS or TFH lymphoma. Methods: We performed a multi-center retrospective study to determine outcomes to 2nd line therapy for adult pts diagnosed between 1.1.09-6.30.18 with PTCL-NOS or TFH lymphoma, who were primary refractory defined by either induction failure, less than CR to initial therapy, or relapse within 6 months (mo) of completion of initial therapy. We performed time to event analysis using Kaplan-Meier method and compared groups using log-rank test. All other statistics were descriptive. Results: Patient and disease characteristics at diagnosis and relapse are summarized in Table 1. We identified 80 eligible pts from 7 US academic centers. Median FU was 17.2 mo from diagnosis (0.5-70). Overall, pts had mostly advanced stage with multiple high-risk features including bone marrow (BM) or extranodal (EN) involvement and B symptoms at diagnosis and R/P. Most pts received CHOP (52%) or CHOEP (24%) as initial therapy. 60% of patients did not attain a CR, while 40% of pts relapsed after initial CR.14% had received a consolidative transplant in 1st CR prior to relapse (almost all autologous hematopoietic cell transplant [HCT]). At R/P, 48% received single agent therapy [mostly romidepsin (15/38)], while 36% received multi-agent salvage therapy [mostly ICE (9/29)]. 13/80 pts were placed on hospice or only received local therapy after R/P. Median OS from diagnosis and following R/P was 19 mo/12.9 mo respectively. Median PFS2 (defined as time from 2nd line therapy to 2nd progression) for pts receiving systemic therapy was 73 days (d) (range 41-175). On univariate and multivariate analysis, there was no significant difference in PFS2 by histologic subtype (74 d for PTCL and 73 d for TFH lymphoma; p=0.29), platelet count Conclusions: Outcomes in this large, well-defined population of primary refractory PTCL-NOS and TFH lymphoma were poor, but better compared to most other retrospective series in R/R T-cell lymphoma. EN disease and advanced stage were common in this cohort of primary refractory pts. Relapse after HCT in CR1 had a particularly poor prognosis. Our findings suggest that single agent therapy following R/P in primary refractory pts and transplant may be beneficial, though our statistical power was limited due to small sample size. In a next step, we plan to expand the cohort and perform genetic/molecular characterization of available biospecimens following central pathology review. Disclosures Rhodes: DAVA Oncology: Honoraria. Olszewski:Spectrum Pharmaceuticals: Research Funding; Genentech: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding. Brammer:Verastem, Inc: Research Funding; Viracta Therapeutics, Inc.: Research Funding; Bioniz Therapeutics, Inc.: Research Funding. Ghosh:TG Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Forty Seven Inc: Research Funding; AstraZeneca: Honoraria, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau. Dwivedy Nasta:Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; 47 (Forty Seven): Research Funding; Rafael: Research Funding; Celgene: Honoraria; ATARA: Research Funding; Aileron: Research Funding; Debiopharm: Research Funding; Millenium/Takeda: Research Funding; Pharmacyclics: Research Funding. Barta:Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Seattle Genetics: Honoraria, Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding.
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- 2019
33. Real world vs. clinical trial outcomes of triple class refractory penta-exposed multiple myeloma (MM)
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Amarendra K. Neppalli, Joshua Mansour, Alyssa Barnstead, Ravi Vij, Sharon Shacham, Ehsan Malek, William Varnado, Shijie Tang, Ajai Chari, Megan Jagosky, Xiwen Ma, Shaji Kumar, Saranya Kodali, Saad Z. Usmani, Swapna Narayana, Ridhi Gupta, Jatin P. Shah, Yubin Kang, Emma C. Scott, Kelly N. Godby, Robert F. Cornell, Paul G. Richardson, Ankit Kansagra, Noa Biran, Ujjawal H. Gandhi, Elizabeth McGehee, Sundar Jagannath, David S. Siegel, Natalie S. Callander, Elvira Umyarova, Sagar Lonial, Luciano J. Costa, Michael Kauffman, Zhubin Gahvari, Arjun Lakshman, Mark A. Fiala, Hari Parameswaran, Barry Paul, Saurabh Chhabra, and Michaela Liedtke
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Class (biology) ,Clinical trial ,Refractory ,Internal medicine ,medicine ,business ,Multiple myeloma - Published
- 2019
34. C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional 'hits' and outcomes with subsequent therapy
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Narendranath, Epperla, Kami J, Maddocks, Mohammed, Salhab, Julio C, Chavez, Nishitha, Reddy, Reem, Karmali, Elvira, Umyarova, Veronika, Bachanova, Cristiana, Costa, Martha, Glenn, Oscar, Calzada, Ana C, Xavier, Zheng, Zhou, Nasheed M, Hossain, Francisco J, Hernandez-Ilizaliturri, Zeina, Al-Mansour, Stefan K, Barta, Saurabh, Chhabra, Frederick, Lansigan, Amitkumar, Mehta, Michael V, Jaglal, Andrew M, Evens, Christopher R, Flowers, Jonathon B, Cohen, Timothy S, Fenske, Mehdi, Hamadani, and Luciano J, Costa
- Subjects
Adult ,Aged, 80 and over ,Male ,Salvage Therapy ,Genes, myc ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Proto-Oncogene Mas ,Translocation, Genetic ,Young Adult ,Treatment Outcome ,Drug Resistance, Neoplasm ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Lymphoma, Large B-Cell, Diffuse ,Aged ,Retrospective Studies - Abstract
The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined.This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy.The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P.001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P.001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in4 months.Patients with MYC-positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC-negative counterparts, but their survival is dismal irrespective of additional "hits" and HCT, representing an unmet medical need. Cancer 2017;123:4411-8. © 2017 American Cancer Society.
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- 2017
35. Diffuse large B-cell lymphoma with primary treatment failure: Ultra-high risk features and benchmarking for experimental therapies
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Deniz Peker, Oscar Calzada, Jonathon B. Cohen, Martha Glenn, Nishitha Reddy, Saurabh Chhabra, Reem Karmali, Luciano J. Costa, Zheng Zhou, Stefan K. Barta, Andrew M. Evens, Hossain Nasheed, Michael Jaglal, Cristiana A Costa, Andreas Forero-Torres, Frederick Lansigan, Christopher R. Flowers, Mehdi Hamadani, Amitkumar Mehta, Elvira Umyarova, Kami J. Maddocks, Ana C. Xavier, Timothy S. Fenske, Zeina Al-Mansour, Francisco J. Hernandez-Ilizaliturri, Veronika Bachanova, Julio C. Chavez, and Narendranath Epperla
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Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Salvage therapy ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Article ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Chemoimmunotherapy ,Recurrence ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Treatment Failure ,Aged ,Retrospective Studies ,Salvage Therapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Lymphoma ,Surgery ,Transplantation ,Clinical trial ,Benchmarking ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Disease Progression ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
The outcomes of patients with DLBCL and primary treatment failure (PTF) in the rituximab era are unclear. We analyzed 331 patients with PTF, defined as primary progression while on upfront chemoimmunotherapy (PP), residual disease at the end of upfront therapy (RD) or relapse
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- 2017
36. Subsequent Treatment Outcomes of Multiple Myeloma Refractory to CD38-Monoclonal Antibody Therapy
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Mark A. Fiala, Megan Jagosky, Ravi Vij, Shaji Kumar, Emma C. Scott, Saurabh Chhabra, Saranya Kodali, Ehsan Malek, Arjun Lakshman, Robert F. Cornell, Elizabeth McGehee, Yubin Kang, Ankit Kansagra, Kelly N. Godby, Zhubin Gahvari, Barry Paul, Ridhi Gupta, Natalie S. Callander, Elvira Umyarova, Parameswaran Hari, Luciano J. Costa, Michaela Liedtke, Joshua Mansour, Amarendra K. Neppalli, Alyssa Barnstead, Saad Z. Usmani, Ujjawal H. Gandhi, and William Varnado
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Poor prognosis ,medicine.medical_specialty ,business.industry ,education ,Immunology ,Treatment outcome ,Daratumumab ,Cell Biology ,Hematology ,medicine.disease ,Pomalidomide ,Biochemistry ,Response to treatment ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Family medicine ,medicine ,030212 general & internal medicine ,Immunomodulatory Agent ,Elotuzumab ,business ,health care economics and organizations ,Multiple myeloma ,medicine.drug - Abstract
Introduction Development of anti-CD38 monoclonal antibody therapies (MoABs), including daratumumab and isatuximab, have drastically changed the therapeutic landscape for management of relapsed and/or refractory multiple myeloma (RRMM). However, there is a paucity of information regarding response to treatment after progression on CD38 MoABs. This collaborative research study (MAMMOTH: Monoclonal Antibodies in Multiple Myeloma: Outcomes after Therapy Failure) investigates the therapeutic choices and outcomes of subsequent treatments after refractoriness to MoABs. Methods Patients from 14 US academic institutions with diagnosis of MM and refractory to daratumumab or isatuximab, administered alone or in combination, were evaluated. Patients were considered refractory to a CD38 MoAB if treated with at least 4 weeks of therapy and had evidence of progressive disease (PD) while on therapy or within 60 days after last dose. Time of progression was defined as time zero (T0). Data was collected by electronic platform and submitted to peer-based quality check for completeness and internal consistency. Results Two hundred and seventy-five patients with MM refractory to CD38 MoAB were evaluated; 249 (90.5%) of those patients who received at least one subsequent line of therapy were included in this analysis. The median age at T0 was 65 years (range 27-90) and 54% were male. At the time of diagnosis, 28% had ISS stage III disease and 29% had high-risk cytogenetics. Patients were heavily pre-treated at T0 with a median of 5 lines of therapy (range 2-17); most (74%) underwent a prior autologous stem cell transplant. The majority of patients were refractory to other anti-myeloma therapies including lenalidomide (78%), pomalidomide (65%), bortezomib (69%) and carfilzomib (45%). In total, 97.1% of patients were exposed to at least one immunomodulatory agent (IMiD) and one proteasome inhibitor (PI), 79.3% were ≥ triple-refractory (refractory to 1 IMiD, 1 PI and 1 CD38 MoAB), while 25.3% were penta-refractory (refractory to 2 IMiDs, 2 PIs and 1 CD38 MoAB). Responses to the next subsequent line of therapy after progression with CD38 MoAB are shown (Table). The overall response rate (ORR; ≥PR) of first regimen post-T0 was 31% with a median progression free survival (PFS) of 3.4 mo and median overall survival (OS) of 9.3 mo. Carfilzomib-based therapy resulted in an ORR of 32% with median PFS 4.2 mo and overall OS of 10.9 mo. The addition of an IMiD to daratumumab yielded an ORR of 37% with median PFS 4.5 mo and OS 12.6 mo. The addition of a PI to daratumumab yielded no responses. Elotuzumab-based therapy had an ORR of 21% with median PFS 2.6 mo and OS 8.3 mo. By multivariate analysis, alkylator-based therapies were found to have the highest ORR (OR 3.1, 95% CI 1.8-5.7, p Conclusions After progression on CD38 MoAB, treatment with carfilzomib-based regimens and the addition of an IMiD to daratumumab-monotherapy resulted in a higher ORR and PFS compared with other regimens. Alkylating agents resulted in the highest ORR but relatively short PFS and OS. The use of elotuzumab and the addition of a PI to daratumumab monotherapy resulted in relatively low response rates. Overall, progression after CD38 MoAB therapy is associated with a poor prognosis and innovative therapeutic strategies are needed. Disclosures Malek: Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau. Paul:Bristol Myer Squibb: Other: Stock and pension plan (past employee). Neppalli:Celgene: Consultancy; Amgen: Consultancy. Liedtke:Amgen/Onyx: Consultancy, Honoraria, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; celgene: Research Funding; BlueBirdBio: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hari:Takeda: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Kite Pharma: Consultancy, Honoraria; Sanofi: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Honoraria. Vij:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy. Costa:Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Research Funding; Abbvie: Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; Sanofi: Honoraria. Kumar:Roche: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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- 2018
37. Natural History of Patients with Multiple Myeloma Refractory to CD38-Targeted Monoclonal Antibody-Based Treatment
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Shaji Kumar, Arjun Lakshman, Alyssa Barnstead, Luciano J. Costa, Zhubin Gahvari, Saad Z. Usmani, Ravi Vij, Emma C. Scott, Saranya Kodali, Mark A. Fiala, Megan Jagosky, Ridhi Gupta, Yubin Kang, Kelly N. Godby, Michaela Liedtke, William Varnado, Ehsan Malek, Elizabeth McGehee, Robert F. Cornell, Ankit Kansagra, Joshua Mansour, Ujjawal H. Gandhi, Amarendra K. Neppalli, Natalie S. Callander, Elvira Umyarova, Parameswaran Hari, Saurabh Chhabra, and Barry Paul
- Subjects
medicine.medical_specialty ,Immunology ,Population ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,education ,health care economics and organizations ,Multiple myeloma ,education.field_of_study ,business.industry ,Daratumumab ,Cell Biology ,Hematology ,medicine.disease ,Pomalidomide ,Transplantation ,Natural history ,Regimen ,030220 oncology & carcinogenesis ,Family medicine ,Bristol myer squibb ,business ,030215 immunology ,medicine.drug - Abstract
Introduction Proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have significantly improved survival in patients with multiple myeloma (MM). Refractoriness to PIs and IMiDs results in poor outcomes with a median survival of about 13 months.Daratumumab and isatuximab are CD38-targeting monoclonal antibodies (MoABs) with remarkable activity in relapsed and refractory MM. The outcome of MM patients in US clinical practice who becomes refractory to CD38 MoABs is unknown. The aim of this multicenter, retrospective study is to investigate the natural history of patients with MM who become refractory to CD38 MoABs (Monoclonal Antibodies in Multiple Myeloma: Outcomes after Therapy Failure: MAMMOTH study). Methods We identified patients from 14 academic institutions in the US with diagnosis of active MM and refractory to daratumumab or isatuximab, administered alone or in combination. Patients were considered refractory to CD38 MoAB if treated with at least 4 weeks of therapy and had evidence of progressive disease (PD) while on therapy or within 60 days after last dose. The time when patients met the above criteria of progression was defined as time zero (T0). Data including patient-disease characteristics and all therapies administered before and after T0 were collected with an electronic platform and submitted to peer-based quality check for completeness and internal consistency. For survival outcome analysis, patients were classified into three groups: "Penta-refractory" (refractory to 1 CD38 MoAB + 2 PIs + 2 IMiDs), "Triple-refractory and quad-refractory" (refractory to 1 CD38 MoAB + 1 PI + 1/2 IMiDs, or 1 CD38 MoAB + 1/2 PIs + 1 IMiD), and "Not triple-refractory" (refractory to 1 CD38 MoAB, and not both of a PI and an IMiD). Responses were evaluated using the IMWG criteria. Results Two hundred and seventy-five patients were included in this study; median age at T0 was 65 years (range 27-90). Fifty five percent of patients were males, 52% had IgG isotype, 29% had ISS stage III disease, and 29% had high-risk cytogenetics at diagnosis. Median interval from diagnosis of MM to T0 was 50.1 months (mo) (range 2.5-230.1). Patients received a median of 4 lines of treatment (1-16) prior to the CD38 MoAB-containing regimen; 72% underwent prior autologous transplant. Daratumumab-refractory patients formed a majority (256, 93.1%) of this cohort. Most of the patients were refractory to lenalidomide (77%), pomalidomide (65%), bortezomib (68%), and carfilzomib (47%). Seventy patients (25.5%) were "penta-refractory" and 148 (53.8%) were "triple-refractory and quad-refractory". Median follow-up from T0 for survivors was 10.6 mo (range 1.9-42.3 mo). The median overall survival (OS) from T0 for the entire cohort was 8.6 mo (95% C.I. 7.2-9.9); OS for the groups based on refractoriness to prior treatments are shown (Figure). Two hundred and forty-nine patients (90.5%) received at least one line of treatment after T0, (median 2, range 1-10). The response rates and depth of responses to each line of treatment post T0 are shown (Table). Among patients who received ≥ 1 subsequent treatment, the median PFS and OS from T0 were 3.4 (95% C.I. 2.8-4.0) mo and 9.3 (95% C.I. 8.1-10.6) mo, respectively; the median OS for the 26 patients who received no further treatment was only 1.3 (95% C.I. 0.6-1.9) mo. By multivariate analysis, penta-refractoriness (HR 2.4, p 2 (HR 2.4, p=0.01) at the onset of CD38-based therapy predicted inferior OS. Conclusions Patients with MM who become refractory to CD38 MoAB are increasingly less responsive to subsequent therapies. While survival is particularly dismal for penta-refractory patients, the outcomes are poor even for patients who are not refractory to other mainstream MM agents. The MAMMOTH study defines a MM population in urgent need for new therapies, and provides benchmark OS, PFS and response data for subsequent investigational therapies in this setting. Disclosures Malek: Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Paul:Bristol Myer Squibb: Other: Stock and pension plan (past employee). Neppalli:Amgen: Consultancy; Celgene: Consultancy. Liedtke:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; BlueBirdBio: Research Funding; celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees. Hari:Amgen Inc.: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Kite Pharma: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Vij:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Kumar:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Costa:Karyopharm: Research Funding; Sanofi: Honoraria; Janssen: Research Funding; BMS: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.
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- 2018
38. Natural History of Patients with Multiple Myeloma Refractory to Elotuzumab and Outcomes of Subsequent Therapy with Anti-CD38 Monoclonal Antibodies
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Shaji Kumar, Natalie S. Callander, William Varnado, Megan Jagosky, Elvira Umyarova, Yubin Kang, Kelly N. Godby, Parameswaran Hari, Barry Paul, Ehsan Malek, Saranya Kodali, Ravi Vij, Ankit Kansgra, Neppalli Amarendra, Robert F. Cornell, Saad Z. Usmani, Elizabeth McGehee, Alyssa Barnstead, Emma C. Scott, Luciano J. Costa, Joshua Mansour, Michaela Liedtke, Mark A. Fiala, Saurabh Chhabra, Ridhi Gupta, Zhubin Gahvari, Arjun Lakshman, and Ujjawal H. Gandhi
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Immunology ,Population ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Elotuzumab ,education ,health care economics and organizations ,Multiple myeloma ,education.field_of_study ,business.industry ,Daratumumab ,Cell Biology ,Hematology ,medicine.disease ,Clinical trial ,Transplantation ,Natural history ,Regimen ,030104 developmental biology ,030220 oncology & carcinogenesis ,Family medicine ,business ,medicine.drug - Abstract
Introduction: Monoclonal antibodies (MoAbs) have shown activity in relapsed and refractory multiple myeloma (MM). Elotuzumab is an anti-SLAMF7 MoAb that synergizes with immunomodulatory agents (IMiDs) and is approved for treatment of relapsed and refractory MM. Anti-CD38 MoAbs (daratumumab, FDA approved and isatuximab, in clinical trials) have also entered the therapeutic MM landscape but little is known about how to best sequence MoAbs and the existence of cross resistance between different classes of MoAbs. We analyzed outcomes of patients who become refractory to elotuzumab with emphasis on the activity of anti-CD38 MoAbs in the post-elotuzumab setting. Methods: We identified patients from 14 academic institutions within the US who were refractory to elotuzumab administered alone or in combination with other agents. Patients were considered refractory to elotuzumab if treated with at least 4 weeks of therapy and had evidence of progressive disease (PD) within 60 days of last dose. Time zero (T0) was defined as point when myeloma became refractory to elotuzumab-containing regimen. Data were collected with an electronic platform and submitted to peer-based quality check for completeness and internal consistency. We analyzed demographics, characteristics of their myeloma and prior therapy including number and type of therapy prior to elotuzumab, duration of elotuzumab therapy, and outcome after becoming refractory to elotuzumab. We performed a multi-variable analysis of these factors to determine significant factors associated with survival post T0. We subsequently identified a subset of patients who received an anti-CD38 MoAb alone or in combination as next or subsequent line of therapy after T0 and report their outcomes. Results: Eighty-nine patients were evaluated. Eighty-six (96.6%) had progression on elotuzumab in combination with IMiD (N=82) or another agent (N=4). Median age at T0 was 65 years (range 28-90), 51% of patients were males, 65% were White, 54% had IgG subtype, 27% had ISS stage III at diagnosis, and 27% had high-risk cytogenetics. Patients received a median of 4 prior lines of treatment (range 1-11) prior to elotuzumab-containing regimen, including 66% who underwent autologous transplant. Sixty-one patients (69%) were refractory to at least one IMiD and one proteasome inhibitor (PI) at T0, classified as double-refractory. Twenty-one (23.6%) were quad-refractory, i.e. refractory to 2 IMiDs and 2 PIs. Twenty-eight patients (31.5%) were refractory to prior anti-CD38 MoAb. The median time from diagnosis to T0 was 59.5 months and duration of elotuzumab therapy was 3 months (range 0.4 - 59.5). Median OS from T0 for the entire cohort was 15.1 months (95% C.I. 9.3-20.9). In multivariate analysis, the only factors affecting OS after T0 were high-risk cytogenetics (HR 3.31, 95% C.I. 1.74-6.27, P Conclusion: Patient who become refractory to elotuzumab have guarded prognosis, particularly dismal among patients also refractory to anti-CD38 MoAb, defining a population with great need for novel therapies. Failure of elotuzumab-based therapy does not preclude disease control with anti-CD38 MoAb, particularly in combination. Disclosures Paul: Bristol Myer Squibb: Other: Stock and pension plan (past employee). Amarendra:Amgen: Consultancy; Celgene: Consultancy. Liedtke:Caelum: Membership on an entity's Board of Directors or advisory committees; celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; BlueBirdBio: Research Funding; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hari:Kite Pharma: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen Inc.: Research Funding; Spectrum: Consultancy, Research Funding. Vij:Karyopharm: Honoraria; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Research Funding; Bristol Myer Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Kumar:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Costa:Karyopharm: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Research Funding; Sanofi: Honoraria; Janssen: Research Funding.
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- 2018
39. Sudden unexpected death in epilepsy
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Mario Cerdan-Trevino, Elvira Umyarova, Edward Maa, and Kenneth Nugent
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,education ,Emergency department ,medicine.disease ,Unexpected death ,humanities ,Epilepsy ,Emergency medicine ,medicine ,Breathing ,Neurology (clinical) ,Cardiopulmonary resuscitation ,Asystole ,business - Abstract
A 57-year-old man with severe mental retardation and epilepsy was found unresponsive. The primary caretaker said that he was on the toilet, rolled his eyes, and stopped breathing. She did not witness either generalized tonic-clonic seizures or trauma. Cardiopulmonary resuscitation was initiated by family members; paramedics found him in asystole. The patient was intubated and flown to the nearest emergency department (ED). However, he remained in asystole and was pronounced dead.
- Published
- 2012
40. MYC+ relapsed and refractory (R/R) diffuse large b-cell lymphoma (DLBCL): Impact of additional hits and outcomes with subsequent therapy
- Author
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Martha Glenn, Mohamed Salhab, Francisco J. Hernandez-Ilizaliturri, Julio C. Chavez, Stefan K. Barta, Veronika Bachanova, Luciano J. Costa, Narendranath Epperla, Timothy S. Fenske, Christopher R. Flowers, Amitkumar Mehta, Mehdi Hamadani, Reem Karmali, Jonathon B. Cohen, Ana C. Xavier, Zheng Zhou, Kami J. Maddocks, Frederick Lansigan, Elvira Umyarova, and Nishitha Reddy
- Subjects
Cancer Research ,Poor prognosis ,Oncology ,Refractory ,business.industry ,hemic and lymphatic diseases ,Cancer research ,Medicine ,Chromosomal translocation ,Newly diagnosed ,business ,medicine.disease ,Diffuse large B-cell lymphoma - Abstract
7541 Background: Translocations involving MYC are a hallmark of poor prognosis among patients with newly diagnosed DLBCL. The impact of MYC translocations with or without additional “hits” involving BCL2 or BCL6 in response to salvage therapy and survival in R/R DLCBL is not well defined. Methods: We performed a multicenter retrospective study of 176 patients with R/R DLBCL failing to achieve CR or relapsing within 6 months after completion of upfront chemoimmunotherapy and for whom FISH information on MYC, BCL2 and BCL6 was available. The objectives were to examine the response to salvage therapy, utilization of hematopoietic cell transplantation (HCT) and survival outcomes in MYC- (n = 120), MYC+ single hit (SH, n = 28), and MYC+ double hit (DH, n = 36) R/R DLBCL. Results: Overall response rate to first salvage therapy and utilization of HCT was comparable between the 3 cohorts (Table). 2-year OS was 0% in MYC+ SH, 8.8% in MYC+ DH and 29.9% in MYC- cases (p = 0.001) without difference in OS between SH and DH (P = 0.8). The higher risk of death for MYC+ SH (HR 1.79, 95% C.I. 1.03-3.11, P = 0.03) and MYC+ DH (HR 1.93, 95% C.I. 1.23-3.00, P = 0.004) persisted after adjustment for covariates. For patients who underwent auto-HCT, 2-year OS was 0% in MYC+ SH, 29.3% in MYC+ DH and 55.4% in MYC- cases (p < 0.001) without significant difference between SH and DH (P = 0.8). All 4 MYC+patients who underwent allo-HCT relapsed in < 4 months. Conclusions: MYC+ R/R DLBCL have similar response to salvage therapy than the MYC- counterparts but dismal survival irrespective of additional “hits” and even if HCT can be performed. MYC+ R/R DLBCL represents an unmet medical need and should be prioritized for clinical trials with novel agents and innovative cellular therapies. [Table: see text]
- Published
- 2017
41. Comparison of patients rehospitalized for heart failure with versus without a history of habitual alcohol consumption
- Author
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Natalia Suvorava, Ragesh Panikkath, Neena Ngo, Elvira Umyarova, Sian Yik Lim, Gary Meyerrose, and Deepa Panikkath
- Subjects
medicine.medical_specialty ,education.field_of_study ,Ejection fraction ,Adult patients ,business.industry ,Population ,Mean age ,General Medicine ,medicine.disease ,University hospital ,Multipatient Studies ,Heart failure ,Internal medicine ,Medicine ,In patient ,business ,education ,Psychiatry ,Alcohol consumption - Abstract
Alcohol paradoxically is known to have a protective and a deleterious effect on the heart. The effect of alcoholism on the growing problem of heart failure (HF) readmissions is not known. This study addressed this issue with a population of adult patients (>20 years old) who were readmitted for HF within 30 days after a hospitalization for HF at a university hospital in West Texas for a period of 5 years. Of the 204 patients with HF who were readmitted, 130 were admitted for HF exacerbations and 74 for unrelated medical conditions. Seventy-two (55%) were men, and the patients' mean age was 67 ± 15 years. Only 32 patients (24%) had a history of alcoholism. The mean age was significantly lower in patients with a history of alcoholism than in those without (62 ± 11 vs. 67 ± 15 years; P = 0.03), and there were more men in the group with a history of alcoholism (78% vs. 52%; P = 0.006). The mean ejection fraction was significantly lower in patients with a history of alcoholism than in those without (35 ± 19% vs. 39 ± 16%, P = 0.04). The length of stay was slightly longer in patients with a history of alcoholism, although the difference was not statistically significant (6 ± 5 vs. 5 ± 4 days; P = 0.52). Although alcohol contributed to only less than one quarter of hospital admissions, these patients were relatively younger and were predominantly males, compared to the sex-matched distribution of patients without a history of alcoholism.
- Published
- 2014
42. Diffuse Large B-Cell Lymphoma with Primary Treatment Failure: Identification of Ultra-High Risk Patients and Benchmarking for Experimental Therapies
- Author
-
Saurabh Chhabra, Reem Karmali, Deniz Peker, Timothy S. Fenske, Zeina Al-Mansour, Julio C. Chavez, Oscar Calzada, Cristiana A Costa, Luciano J. Costa, Veronika Bachanova, Andrew G. Evans, Francisco J. Hernandez-Ilizaliturri, Frederick Lansigan, Kami J. Maddocks, Jonathon B. Cohen, Christopher R. Flowers, Elvira Umyarova, Amitkumar Mehta, Nasheed Hossain, Mehdi Hamadani, Andre Forero-Torres, Zheng Zhou, Ana C. Xavier, Martha Glenn, Stefan K. Barta, Nishitha Reddy, Michael Jaglal, and Narendranath Epperla
- Subjects
medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Salvage therapy ,Cell Biology ,Hematology ,Benchmarking ,Ultra high risk ,medicine.disease ,Biochemistry ,Transplantation ,Clinical trial ,Family medicine ,medicine ,Primary treatment ,education ,business ,Diffuse large B-cell lymphoma - Abstract
Introduction: Most patients (pts) with diffuse large B cell lymphomas (DLBCL) are cured with first line chemoimmunotherapy including an anthracycline and rituximab. Pts who obtain complete remission (CR) but latter relapse often can be cured with salvage therapy and autologous hematopoietic cell transplantation (auto-HCT). This management paradigm often is applied to pts with primary treatment failure (PTF). However, this group is heterogeneous and detailed data on outcomes in current era is needed to identify the DLBCL pts for whom novel therapeutic strategies should be designed. Methods: Fifteen US academic medical centers contributed pts to the REgistry of diFfuse large B cell lymphoma with prImary treatmeNt failurE (REFINE) collaboration. REFINE retrospectively captured patient, disease and treatment characteristics and treatment response as assessed by treating physician. Eligible pts were ≥ 18 years diagnosed with DLBCL during 2008-2015, who received upfront cheomoimmunotherapy including anthracycline and CD20-directed antibody and developed one of 3 patterns of PTF: relapse < 6 months following CR (early relapse- ER); only partial remission (PR) or stable disease (SD) with upfront therapy (residual disease-RD); progressive disease (PD) while receiving upfront therapy (primary progression-PP). Pts with HIV infection, primary CNS lymphoma or lymphoma transforming from a more indolent histology were excluded. Results: Patient characteristics for the 331 cases are summarized in Table 1. Median follow up of survivors was 18.9 months. R-CHOP was the upfront treatment for 87.6% of pts. Nearly all pts (94.6%) received salvage therapy after PTF and prior to any HCT, with a median of 1 and range 0 to 5 regimens. Response to first salvage regimen was CR in 19.9%, PR in 21.8%, SD in 9.0% and PD in 40.8%. Only 15.1% of pts were enrolled in clinical trials. One hundred and thirty-two pts (39.9%) underwent auto-HCT and 33 (10.0%) allogeneic-HCT (8 after failure of auto-HCT). Two-year overall survival (OS) from time of PTF was 45.5% (95% C.I. 34.5-56.5%) for ER, 30.6% (95% C.I. 20.0-41.2%) for RD and 18.5% (95% C.I. 11.4-25.6%) for PP (P Conclusions: Pts with DLBCL experiencing PTF have poor prognosis but low clinical trial participation even when treated in academic centers. Pts with PP disease, intermediate-high/high NCCN-IPI at time of PTF or with c-myc(+) tumors constitute a UHR category with dismal outcomes on existing therapies. REFINE provides benchmarking for future experimental agents targeting this population. UHR pts represent an unmet medical need and should receive high priority for development of new drugs and cellular therapies. Table 1. Table 1. Figure 1. Figure 1. Disclosures Chavez: Janssen: Speakers Bureau. Reddy:INFINITY: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Karmali:Celgene: Speakers Bureau. Calzada:Seattle Genetics: Research Funding. Barta:Janssen: Honoraria, Speakers Bureau; Celgene, Merck, Seattle Genetics: Research Funding. Lansigan:Spectrum: Consultancy, Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Teva: Research Funding. Flowers:Roche: Consultancy, Research Funding; Acerta: Research Funding; TG Therapeutics: Research Funding; NIH: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Infinity: Research Funding; Gilead: Consultancy, Research Funding; Millenium/Takeda: Research Funding; ECOG: Research Funding; AbbVie: Research Funding; Mayo Clinic: Research Funding; Genentech: Consultancy, Research Funding. Fenske:Seatle Genetics: Honoraria; Millennium/Takeda: Research Funding; Celgene: Honoraria; Pharmacyclics: Honoraria. Cohen:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hamadani:Takeda: Research Funding. Costa:Sanofi: Honoraria, Research Funding.
- Published
- 2016
43. Primary Failure Diffuse Large B Cell Lymphoma: Early Autologous or Donor Hematopoietic Cell Transplantation Not Effective in Patients with Ultra-High Risk Features
- Author
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Cristiana A Costa, Timothy S. Fenske, Zeina Al-Mansour, Saurabh Chhabra, Luciano J. Costa, Reem Karmali, Michael Jaglal, Narendranath Epperla, Jonathon B. Cohen, Mehdi Hamadani, Kami J. Maddocks, Francisco J. Hernandez-Ilizaliturri, Frederick Lansigan, Nishitha Reddy, Zheng Zhou, Julio C. Chavez, Andrew G. Evans, Veronika Bachanova, Elvira Umyarova, Nasheed Hossain, Oscar Calzada, Ana C. Xavier, Martha Glenn, Stefan K. Barta, and Christopher R. Flowers
- Subjects
medicine.medical_specialty ,education.field_of_study ,Hematopoietic cell ,business.industry ,Immunology ,Population ,Salvage therapy ,Cell Biology ,Hematology ,Ultra high risk ,medicine.disease ,Biochemistry ,Treatment characteristics ,Transplantation ,Family medicine ,medicine ,In patient ,education ,business ,Diffuse large B-cell lymphoma - Abstract
Introduction: Modern chemoimmunotherapy cures the majority of patients (pts) with newly diagnosed diffuse large B cell lymphomas (DLBCL). The paradigm for pts who relapse has been salvage chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) when chemosensitive disease. This approach is often also applied to pts with primary treatment failure (PTF), although this group is heterogeneous and outcomes of HCT in this population have not been well described. Methods: Fifteen US academic medical centers contributed pts to the REgistry of diFfuse large B cell lymphoma with prImary treatmeNt failurE (REFINE) collaboration. REFINE retrospectively captured patient, disease and treatment characteristics and response as assessed by treating center. Eligible pts were ≥ 18 years diagnosed with DLBCL during 2008-2015, who received upfront therapy including anthracycline and CD20-directed antibody and developed one of 3 patterns of PTF: relapse < 6 months following CR (early relapse- ER); only partial remission (PR) or stable disease (SD) with upfront therapy (residual disease-RD); progressive disease (PD) while receiving upfront therapy (primary progression-PP). Pts with HIV infection, primary CNS lymphoma or lymphoma transforming from a more indolent histology were excluded. Results: Among 331 cases included in REFINE, patterns of PTF were ER in 95 (28.7%), RD in 92 (27.8%) and PP in 144 (43.5%) pts. Salvage therapy was administered to 94.6% of pts. We analyzed the 157 (47.4%) PTF pts who subsequently underwent HCT, 132 auto-HCT and 33 allo-HCT (8 after failure of auto-HCT) (Table). Nearly half of pts were in CR at transplant, after 1-2 lines of salvage therapy. Among all pts receiving auto-HCT, 2-year progression-free survival (PFS) from time of transplant was 38.4% (95% C.I. 29.6-47.2%) and overall survival (OS) 54.9% (95% C.I. 44.9-64.9%). Two-year OS from auto-HCT was affected by pattern of PTF: 71.3% for ER, 55.0% for RD and 41.7% for PP (P=0.05). OS at 2-years was 23.7% for auto-HCT pts with germinal center B (GCB)type,c-myc(+) (by FISH) tumors vs. 66.7% for GCB, c-myc (-), vs. 67.8% for non-germinal center (NGC) (P=0.01). Auto-HCT pts with intermediate-high/high NCCN-IPI at time of PTF had 2-year OS of 28.6% vs. 66.0% for intermediate-low and 80.9% for low risk (P Conclusions: Pts with DLBCL experiencing PTF and 2 or more UHF features have dismal outcome after auto-HCT and should be targeted for experimental modalities of cellular therapy. Outcomes of allo-HCT in DLBCL with PTF are poor, due to rapid and fatal relapses. Table. Table. Figure. Figure. Disclosures Costa: Sanofi: Honoraria, Research Funding. Reddy:INFINITY: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Karmali:Celgene: Speakers Bureau. Chavez:Janssen: Speakers Bureau. Calzada:Seattle Genetics: Research Funding. Barta:Janssen: Honoraria, Speakers Bureau; Celgene, Merck, Seattle Genetics: Research Funding. Flowers:Pharmacyclics, LLC, an AbbVie Company: Research Funding; Mayo Clinic: Research Funding; Acerta: Research Funding; Roche: Consultancy, Research Funding; TG Therapeutics: Research Funding; ECOG: Research Funding; Genentech: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; NIH: Research Funding; Infinity: Research Funding; Millenium/Takeda: Research Funding; AbbVie: Research Funding. Fenske:Seatle Genetics: Honoraria; Pharmacyclics: Honoraria; Celgene: Honoraria; Millennium/Takeda: Research Funding. Cohen:Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Hamadani:Takeda: Research Funding.
- Published
- 2016
44. Problematic PEG: A Case of Enteral Feeding Tube Seeding Malignancy to the Abdominal Wall
- Author
-
Jilian R. Sansbury, Brad Keith, Elvira Umyarova, and Keisuke Shirai
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,Malignancy ,medicine.disease ,Enteral administration ,Surgery ,Abdominal wall ,medicine.anatomical_structure ,PEG ratio ,medicine ,Seeding ,business ,Feeding tube - Published
- 2015
45. Anti CD20 Radioimmunotherapy and mTOR Inhibition in Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas
- Author
-
Elvira Umyarova, Robert K. Stuart, Alice S. Mims, Saurabh Chhabra, and Luciano J. Costa
- Subjects
Transplantation ,business.industry ,medicine.medical_treatment ,Hematology ,Hematopoietic stem cell transplantation ,medicine.anatomical_structure ,Radioimmunotherapy ,Reduced Intensity Conditioning ,Relapsed refractory ,medicine ,Cancer research ,Anti cd20 ,business ,PI3K/AKT/mTOR pathway ,B cell - Published
- 2015
46. Factors Affecting Mortality In COPD Exacerbations In ICU Patients
- Author
-
Chok Limsuwat, Nopakoon Nantsupawat, Kenneth Nugent, Elvira Umyarova, and Kamonpun Ussavarungsi
- Subjects
medicine.medical_specialty ,Icu patients ,COPD ,business.industry ,Emergency medicine ,medicine ,business ,medicine.disease - Published
- 2012
47. FatalClostridium SepticumInfection in a Patient with a Hematological Malignancy
- Author
-
Elvira Umyarova, Ragesh Panikkath, Deepa Panikkath, Venu Madhav Konala, and Fred Hardwicke
- Subjects
medicine.medical_specialty ,Myeloid ,Erythema ,biology ,business.industry ,medicine.medical_treatment ,Consolidation Chemotherapy ,General Medicine ,030204 cardiovascular system & hematology ,Refractory hypotension ,biology.organism_classification ,Surgery ,Clostridium septicum ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Amputation ,medicine ,030212 general & internal medicine ,medicine.symptom ,business ,Surgical incision ,Right Thigh - Abstract
A 49-year-old woman with acute myeloid transformation of myelodysplastic syndrome was admitted with mild erythema and pain in the right thigh and left forearm. She was doing well and had been discharged the previous day after consolidation chemotherapy. Examination showed only mild erythema and tenderness of the right thigh. She was started on broad-spectrum antibiotics. Discoloration progressed rapidly, and within hours the right femoral and left brachial pulses were not palpable. She was taken to the operating room for a suspicion of embolic arterial occlusion. Surgical incision, however, revealed extensive necrosis of the tissues with the presence of gas. Her relatives did not want her to undergo amputation. The patient developed refractory hypotension and died within 15 hours of presentation. Blood samples later tested positive for Clostridium septicum. This case is presented to create awareness about the subtle presentation and rapid progression of this infection, which can lead to death in less than 24 hours.
- Published
- 2014
48. EBV Negative NK/T-Cell PTLD of the Distal Ileum in a Renal Transplant Recipient
- Author
-
Meghan Steiner and Elvira Umyarova
- Subjects
Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Hepatology ,business.industry ,Renal transplant ,Distal ileum ,T cell ,Gastroenterology ,Medicine ,business - Published
- 2015
49. Factors affecting mortality in patients with COPD exacerbations requiring ICU admission
- Author
-
Kenneth Nugent, Elvira Umyarova, Kamonpun Ussavarungsi, Chok Limsuwat, and Nopakoon Nantsupawat
- Subjects
lcsh:RC705-779 ,medicine.medical_specialty ,COPD ,Exacerbation ,business.industry ,medicine.medical_treatment ,Mortality rate ,lcsh:Diseases of the respiratory system ,Odds ratio ,medicine.disease ,mortality ,Confidence interval ,Blood pressure ,Internal medicine ,Intensive care ,medicine ,risk factors ,Intubation ,business ,Intensive care medicine ,acute flare - Abstract
Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often require hospital admission and have a significant mortality rate. Patients with AECOPD who need intensive care (ICU) have higher mortality rates. Identifying factors associated with increased mortality might change approaches to treatment and improve communication with patients’ families about prognosis. Methods: Patients with AECOPD (ICD 9 code 491.21) directly admitted to the ICU between 1/1/2006 and 12/31/2010 were retrospectively reviewed. The inclusion criteria were age 45 years or older, diagnosis of AECOPD, and admission to an ICU. The exclusion criteria included any history of another respiratory disease or decompensated cardiac disease. The primary goal was to determine factors which affect survival. Result: Two hundred and seventeen patients were included this study. The mean ages were 70.4±10.4 years in the in-hospital death group and 66.4±10.9 years in the survivors. The overall mortality rate was 12%. Multivariate analysis showed that the mortality rate was significantly associated with a low mean arterial blood pressure (MAP) (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.86-0.96), an intubation event (OR 6.12, 95% CI 1.24-30.87), and an elevated blood urea nitrogen (BUN) (OR 1.06, 95% CI 1.01-1.12) (p
- Published
- 2013
50. Gastric Adenocarcinoma Presented with Unilateral Lower Extremity Lymphoedema
- Author
-
Shivani Kandukuri, El-Sayed Abo-Salem, Ariwan Rakvit, and Elvira Umyarova
- Subjects
medicine.medical_specialty ,Gastric adenocarcinoma ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,business - Published
- 2011
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