Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma

AbstractThis population pharmacokinetics analysis evaluated the target-mediated drug disposition of inotuzumab ozogamicin (InO) through an empirical time-dependent clearance (CLt) term and identified potential covariates that may be important predictors of variability in InO distribution and elimination. This analysis was conducted by pooling data from 2 studies of single-agent InO in patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL), 3 studies of single-agent InO, 5 studies of InO plus rituximab (R-InO), and 1 study of R-InO plus chemotherapy in patients with R/R B-cell non-Hodgkin lymphoma (NHL). Pharmacokinetic data included 8361 InO concentration –time observations that were modeled using nonlinear mixed-effects analysis. Covariate relations were identified using generalized additive modeling on base model parameters and then tested in a stepwise manner via covariate modeling. InO concentration was described with a 2-compartment model with linear and time-dependent clearance components. Based on the final model, baseline body surface area was a covariate of the linear and time-dependent clearance components and volume of distribution in the central compartment; baseline percentage of blasts in the peripheral blood was a covariate of the decay coefficient of the time-dependent clearance term (CLt); and concomitant rituximab treatment was a covariate of the linear clearance component (CL1). The magnitude of change of each pharmacokin...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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ConclusionsOur results provide novel insights that association between CAR-T treatment dose and severe CRS incidence only exists in patients less than or equal to 25  years old. Severe CRS incidence is associated with baseline tumor burden which indicates that tumor burden needs to be controlled with induced chemotherapy before CAR-T treatment.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
A promising and expensive type of immunotherapy, called CAR T-cell therapy, is now covered by Medicare. This news may affect mesothelioma patients in the future. Chimeric antigen receptor T-cell, or CAR T-cell, therapy involves the laboratory reprogramming of a patient’s T cells, which are a type of white blood cell responsible for protecting the body against infection and disease. The T cells are genetically modified to better recognize and attack cancer. The U.S. Food and Drug Administration has approved the immunotherapy procedure for non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia. It is...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
In conclusion, T cells from lymphoma patients are reduced in number and have functional defects following treatment with certain chemotherapy regimens, also reducing AFM11 efficacy. Importantly, AFM11 was still able to trigger B-cell-directed T-cell immunity in all treatment groups.
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion: This prospective multicenter study provides information on the current incidence and outcome of IFD in the real life setting. Practice variation between the centers may help to ultimately improve antifungal management in children at highest risk for IFDs. Introduction Available data on the incidence and outcome of invasive fungal diseases (IFD) in children treated for a hematological malignancy or undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are mostly based on single site, retrospective studies or on studies performed prior to the availability of newer compounds such as broad-sp...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Abstract We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n&thins...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
Conclusion: While providing potential clinical benefit, CAR T cell therapy utilizes resources across the therapeutic spectrum, and increasing use of this therapeutic modality can create challenges in institutional resource capacity. Identifying these resources will allow for better care delivery and allocation of funds. Further refinement of CAR T cell products and improvements in CAR T cell-related toxicity management may permit safer delivery of this therapy and reduce costs per patient. Additional analysis of resource utilization among patients treated with commercial CAR T cell products, as well as comparison with alte...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Overuse, Costs, and Utilization of Health Services Source Type: research
Conclusions: In patients with r/r aggressive B-NHL and predominantly progressive disease following ≥2 cycles of platinum-based S1 chemotherapy, blinatumomab monotherapy as S2 therapy induced CMR/PMR in 37% of patients and led to HSCT in 20%. When considering that 66% of the patients enrolled had progressive disease and that 47% received the therapeutic dose, blinatumomab showed promising efficacy consistent with the efficacy and safety demonstrated in earlier blinatumomab B-NHL trials and potentially offers a treatment option for patients unresponsive to standard salvage regimens.DisclosuresCoyle: Amgen Inc.: Other: non...
Source: Blood - Category: Hematology Authors: Tags: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials: New Agents Source Type: research
This study was approved by the institutional review board of Komaki City Hospital. We assessed the prevalence and trends of multiple measures of intensive EOL care established in the peer-reviewed literature. Intensive EOL care was defined as the occurrence of at least one of the following acts: 1) cardiopulmonary resuscitation (CPR) in the last 30 days of life, 2) intubation in the last 30 days of life, 3) intensive care unit (ICU) admission in the last 30 days of life, 4) chemotherapy use within the last 14 days of life, 5) receiving red cell transfusions within the 7 days before death, and 6) receiving platelet transfus...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Poster I Source Type: research
Conclusions: DLI obtained from unmanipulated, GCSF-primed whole-blood is a safe and affordable adoptive cell therapy. It is effective and improves mixed chimerism after HSCT, while it was less effective for overt relapse.DisclosuresGomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.
Source: Blood - Category: Hematology Authors: Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III Source Type: research
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