11 results on '"Singavi AK"'
Search Results
2. Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.
- Author
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Roeker LE, Fox CP, Eyre TA, Brander DM, Allan JN, Schuster SJ, Nabhan C, Hill BT, Shah NN, Lansigan F, Yazdy M, Cheson BD, Lamanna N, Singavi AK, Coombs CC, Barr PM, Skarbnik AP, Shadman M, Ujjani CS, Tuncer HH, Winter AM, Rhodes J, Dorsey C, Morse H, Kabel C, Pagel JM, Williams AM, Jacobs R, Goy A, Muralikrishnan S, Pearson L, Sitlinger A, Bailey N, Schuh A, Kirkwood AA, and Mato AR
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- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Dose-Response Relationship, Drug, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Patient Safety, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Retrospective Studies, Treatment Outcome, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Drug-Related Side Effects and Adverse Reactions prevention & control, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Practice Patterns, Physicians' standards, Sulfonamides therapeutic use, Tumor Lysis Syndrome prevention & control
- Abstract
Purpose: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice., Experimental Design: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected., Results: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV , 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose., Conclusions: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety., (©2019 American Association for Cancer Research.)
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- 2019
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3. A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL.
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Mato AR, Roeker LE, Eyre TA, Nabhan C, Lamanna N, Hill BT, Brander DM, Barr PM, Lansigan F, Cheson BD, Singavi AK, Yazdy MS, Shah NN, Allan JN, Bhavsar EB, Rhodes J, Kennard K, Schuster SJ, Williams AM, Skarbnik AP, Goy AH, Goodfriend JM, Dorsey C, Coombs CC, Tuncer H, Ujjani CS, Jacobs R, Winter AM, Pagel JM, Bailey N, Schuh A, Shadman M, Sitlinger A, Weissbrot H, Muralikrishnan S, Zelenetz A, Kirkwood AA, and Fox CP
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal pharmacology, Antineoplastic Agents pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Progression-Free Survival, Retrospective Studies, Sulfonamides pharmacology, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Sulfonamides therapeutic use
- Abstract
Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings., (© 2019 by The American Society of Hematology.)
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- 2019
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4. Immunogenomic Landscape Contributes to Hyperprogressive Disease after Anti-PD-1 Immunotherapy for Cancer.
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Xiong D, Wang Y, Singavi AK, Mackinnon AC, George B, and You M
- Abstract
Although PD-1-blocking immunotherapies demonstrate significant therapeutic promise, a subset of the patients could develop hyperprogressive disease (HPD) with accelerated tumor growth after anti-PD1 immunotherapy. To elucidate the underlying mechanisms, we compared the mutational and transcriptional landscapes between the pre- and post-therapy tumors of two patients developing HPD after anti-PD-1 immunotherapy. In post-therapy HPD tumors, somatic mutations were found in known cancer genes, including tumor suppressor genes such as TSC2 and VHL, along with transcriptional upregulation of oncogenic pathways, including IGF-1, ERK/MAPK, PI3K/AKT, and TGF-β. We found that post-therapy HPD tumors were less immunogenic than pre-therapy tumors, concurrent with an increased presence of ILC3 cells, a subset of innate lymphoid cells. We also developed a gene expression signature predictive of HPD. In summary, we identified the genomics and immune features associated with HPD, which may help identify patients at risk of adverse clinical outcome after anti-PD-1 immunotherapy., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2018
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5. Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States.
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Mato AR, Thompson M, Allan JN, Brander DM, Pagel JM, Ujjani CS, Hill BT, Lamanna N, Lansigan F, Jacobs R, Shadman M, Skarbnik AP, Pu JJ, Barr PM, Sehgal AR, Cheson BD, Zent CS, Tuncer HH, Schuster SJ, Pickens PV, Shah NN, Goy A, Winter AM, Garcia C, Kennard K, Isaac K, Dorsey C, Gashonia LM, Singavi AK, Roeker LE, Zelenetz A, Williams A, Howlett C, Weissbrot H, Ali N, Khajavian S, Sitlinger A, Tranchito E, Rhodes J, Felsenfeld J, Bailey N, Patel B, Burns TF, Yacur M, Malhotra M, Svoboda J, Furman RR, and Nabhan C
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Disease Management, Drug Resistance, Neoplasm, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Recurrence, Sulfonamides administration & dosage, Sulfonamides adverse effects, Survival Analysis, Treatment Outcome, Tumor Lysis Syndrome etiology, Antineoplastic Agents therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Sulfonamides therapeutic use
- Abstract
Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV , 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study., (Copyright© 2018 Ferrata Storti Foundation.)
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- 2018
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6. Daratumumab in Primary Effusion Lymphoma.
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Shah NN, Singavi AK, and Harrington A
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- ADP-ribosyl Cyclase 1 metabolism, Bone Marrow pathology, HIV Infections complications, Herpesvirus 8, Human isolation & purification, Humans, Lymphoma, Primary Effusion therapy, Lymphoma, Primary Effusion virology, Male, Middle Aged, Recurrence, Viral Load, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Lymphoma, Primary Effusion drug therapy
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- 2018
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7. Graft-versus-host disease-associated hepatic portal venous gas.
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Singavi AK and Shah NN
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- Allografts, Graft vs Host Disease metabolism, Humans, Lymphoma, T-Cell diagnostic imaging, Lymphoma, T-Cell mortality, Male, Middle Aged, Gases metabolism, Graft vs Host Disease diagnostic imaging, Hematopoietic Stem Cell Transplantation, Lymphoma, T-Cell therapy, Portal Vein diagnostic imaging, Portal Vein metabolism, Tomography, X-Ray Computed
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- 2018
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8. Current challenges in the management of essential thrombocythemia.
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Kleman A, Singavi AK, and Michaelis LC
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- Female, Humans, Male, Pregnancy, Algorithms, Pregnancy Complications, Hematologic diagnosis, Pregnancy Complications, Hematologic therapy, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential therapy
- Abstract
Essential thrombocythemia (ET), an uncommon blood cancer, is one of the classic myeloproliferative neoplasms, a category that also includes polycythemia vera and primary myelofibrosis. All 3 diseases are clonal hematopoietic stem cell disorders. Since 2005, when scientists discovered a molecular aberration driving clonal hematopoiesis in polycythemia vera, our understanding of the genomic underpinnings of these conditions has increased rapidly. Over the last decades, primary prevention of thrombotic and hemorrhagic complications has improved the lives of patients with ET, and the ability to characterize the disease by the presence or absence of molecular mutations has lent precision to our prognostic models. This review outlines a modern approach to the diagnosis and treatment of ET. It highlights the 2016 World Health Organization standards for differentiating the disease from primary myelofibrosis, which is key for an accurate prognosis. It also describes the current risk stratification models and discusses the vascular and hemorrhagic risks that affect patients with this chronic condition, including younger individuals and pregnant women. Finally, it outlines a simple-to-follow treatment algorithm that is based on an understanding of the vascular risks and provides a foundation for discussing treatment choices with patients.
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- 2017
9. Red cell storage age policy for patients with sickle cell disease: A survey of transfusion service directors in the United States.
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Karafin MS, Singavi AK, Irani MS, Puca KE, Baumann Kreuziger L, Simpson P, and Field JJ
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- Demography, Hospitals, Humans, Time Factors, United States, Anemia, Sickle Cell blood, Blood Banks, Blood Preservation, Blood Transfusion, Erythrocytes cytology, Surveys and Questionnaires
- Abstract
In patients with sickle cell disease (SCD), the effects of the red cell storage lesion are not well defined. The objective of this study was to determine the prevalence of transfusion services that limit red cell units by storage age for patients with SCD. We developed a 22 question survey of transfusion service director opinions and their corresponding blood bank policies. Target subjects were systematically identified on the AABB website. Responses were recorded in SurveyMonkey and summarized using standard statistical techniques. Ninety transfusion service directors responded to the survey. Response rate was 22%. Only 23% of respondents had storage age policies in place for patients with SCD, even though 36% of respondents consider older units to be potentially harmful in this patient population. Of those with a policy, a less-than 15 day storage age requirement was most often used (75%), but practices varied, and most respondents (65%) agreed that evidence-based guidelines regarding storage age are needed for patients with SCD. Policies, practices and opinions about the risks of older units for patients with SCD vary. As patients with SCD may have unique susceptibilities to features of the red cell storage lesion, prospective studies in this population are needed to determine best practice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
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- 2016
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10. Safety of outpatient autologous hematopoietic cell transplantation for multiple myeloma and lymphoma.
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Graff TM, Singavi AK, Schmidt W, Eastwood D, Drobyski WR, Horowitz M, Palmer J, Pasquini M, Rizzo DJ, Saber W, Hari P, and Fenske TS
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- Adult, Aged, Cohort Studies, Female, Hematopoietic Stem Cell Transplantation methods, Humans, Lymphoma therapy, Male, Middle Aged, Multiple Myeloma therapy, Outpatients, Retrospective Studies, Young Adult, Lymphoma surgery, Multiple Myeloma surgery, Transplantation Conditioning methods, Transplantation, Autologous methods
- Abstract
Autologous hematopoietic cell transplantation (Auto-HCT) is commonly an in-patient procedure. However, Auto-HCT is increasingly being offered on an outpatient basis. To better characterize the safety of outpatient Auto-HCT, we compared the outcome of 230 patients who underwent Auto-HCT on an in-patient vs outpatient basis for myeloma or lymphoma within a single transplant program. All outpatient transplants occurred in a cancer center day hospital. Hematopoietic recovery occurred earlier in the outpatient cohort, with median time to neutrophil recovery of 10 vs 11 days (P<0.001) and median time to platelet recovery of 19 vs 20 days (P=0.053). Fifty-one percent of the outpatient cohort never required admission, with this percentage increasing in later years. Grade 3-4 non-hematologic toxicities occurred in 29% of both cohorts. Non-relapse mortality at 1 year was 0% in the outpatient cohort and 1.5% in the in-patient cohort (P=0.327). Two-year PFS was 62% for outpatient vs 54% for in-patient (P=0.155). One- and two-year OS was 97% and 83% for outpatient vs 91% and 80% for in-patient, respectively (P=0.271). We conclude that, with daily outpatient evaluation and aggressive supportive care, outpatient Auto-HCT can result in excellent outcomes for myeloma and lymphoma patients.
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- 2015
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11. Post-transplant lymphoproliferative disorders.
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Singavi AK, Harrington AM, and Fenske TS
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- Antibodies, Monoclonal, Murine-Derived therapeutic use, Antiviral Agents therapeutic use, Epstein-Barr Virus Infections complications, Humans, Immunotherapy, Adoptive, Lymphoproliferative Disorders epidemiology, Lymphoproliferative Disorders prevention & control, Prognosis, Risk Factors, Rituximab, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders etiology, Lymphoproliferative Disorders therapy, Organ Transplantation adverse effects
- Abstract
Post-transplant lymphoproliferative disorders (PTLD) are a serious complication after solid organ or allogeneic hematopoietic stem cell transplantation and include a range of diseases from benign proliferations to malignant lymphomas. Risk factors for developing PTLD include Epstein-Barr virus (EBV) infection, recipient age, transplanted organ, type of immunosuppression, and genetics. Uncontrolled proliferation of EBV-infected B cells is implicated in EBV-positive PTLD, whereas the pathogenesis of EBV-negative PTLD may be similar to non-Hodgkin's lymphoma in the general population. The World Health Organization (WHO) classifies PTLD into four categories: early lesions, polymorphic PTLD, monomorphic PTLD, and classical Hodgkin's lymphoma (cHL). Treatment is aimed at cure of PTLD, while maintaining transplanted organ function. However, there are no established guidelines for the treatment of PTLD. Immune suppression reduction (ISR) is the first line of treatment in most cases, with more recent data suggesting early use of rituximab. In more aggressive forms of PTLD, upfront chemotherapy may offer a better and more durable response. Sequential therapy using rituximab followed by chemotherapy has demonstrated promising results and may establish a standard of care. Novel therapies including anti-viral agents, adoptive immunotherapy, and monoclonal antibodies targeting cytokines require further study in the prevention and treatment of PTLD.
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- 2015
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