Changes in intravenous immunoglobulin (IVIG) usage for hypogammaglobulinemia (HG) after implementation of a stewardship program.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19225-e19225
Author(s):  
Benjamin Avi Derman ◽  
Zachary Schlei ◽  
Kate M. Mullane ◽  
Sandeep Parsad ◽  
Randall W Knoebel
Keyword(s):  
Cost Savings ◽  
Hematologic Malignancies ◽  
Antibiotic Usage ◽  
Hospitalization Rate ◽  
Antibiotic Administration ◽  
T Cell Therapy ◽  
Stewardship Program ◽  
Car T ◽  
High Level ◽  
Igg Level

e19225 Background: IVIG is used to replenish immunoglobulins in HG due to hematologic malignancies (HM) or their treatment (stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T)), in an effort to reduce the risk of infections. There is limited high-level evidence to support this use, and IVIG supplies are limited with a recent shortage leading to restricted allotments. We report the results of a stewardship program designed to safely reduce IVIG usage. Methods: An IVIG stewardship plan (ISP) was implemented with the following requirements for IVIG administration: IgG level < 400 mg/dL (corrected for paraprotein) for post-ASCT and post-CAR-T patients, or IgG < 400 mg/dL with evidence of a bacterial infection within the last 3 months that required hospitalization or an emergency department encounter for those with HM. We evaluated the amount of IVIG administered, the incidence of infections, and antibiotic administration before and after implementation of an ISP. Results: In the 3 months pre-ISP, HG accounted for 38% (72/188) of total IVIG orders. 86 pts received IVIG for HG in the 3 months pre-ISP. The amount of IVIG given decreased from 1907 g/month pre-ISP to 670 g/month post-ISP; estimated cost savings in IVIG was $57,561/month. The pre-ISP median IgG level prior to dosing of IVIG was 550 (range 40-1189) mg/dL. Compared to pre-ISP, pts who stopped receiving IVIG post-ISP had lower median pre-dose IgG (444, range 93-819 mg/dL, p<0.05), infections/patient-months (14/141 vs 56/255, p<0.001), antibiotic usage (12/47 vs 44/86, p<0.05), and hospitalization rate for infection (4/55 vs 21/86, p<0.05); no deaths occurred. For those receiving IVIG post-ISP, adherence to guidelines was 64%. Compared to pre-ISP, median pre-dose IgG was lower (328, range 51-1011 mg/dL, p<0001), infections/patient-months decreased (27/163 vs 56/255, p<0.001), and antibiotic usage, hospitalization rate for infection, and deaths from infection all remained stable. Conclusions: An ISP for HG led to a dramatic and sustainable decrease in IVIG usage, primarily by selecting out patients who are low risk for infection after discontinuation of IVIG. Such an ISP is replicable and warrants adoption.

scholarly journals Changes in Intravenous Immunoglobulin Usage for Hypogammaglobulinemia After Implementation of a Stewardship Program

2020 ◽  
pp. OP.20.00312
Author(s):  
Benjamin A. Derman ◽  
Zachary Schlei ◽  
Sandeep Parsad ◽  
Kathleen Mullane ◽  
Randall W. Knoebel
Keyword(s):  
Intravenous Immunoglobulin ◽  
Cost Savings ◽  
Hematologic Malignancies ◽  
Hospitalization Rate ◽  
T Cell Therapy ◽  
Stewardship Program ◽  
Car T ◽  
History Of ◽  
Igg Level ◽  
Ivig Administration

PURPOSE: Intravenous immunoglobulin (IVIG) is used to replenish immunoglobulins in hypogammaglobulinemia (HG) caused by hematologic malignancies (HM) or their treatment (autologous stem-cell transplantation [ASCT] and chimeric antigen receptor T-cell therapy [CAR-T]), in an effort to reduce the risk of infections. However, there is limited evidence to support this use, and IVIG supplies are limited and shortages are common. METHODS: An IVIG stewardship program (ISP) was implemented with the following requirements for IVIG administration: immunoglobulin G (IgG) level < 400 mg/dL (corrected for paraprotein) for post-ASCT and post–CAR-T patients, or IgG < 400 mg/dL with a history of a bacterial infection within the preceding 3 months for those with HM. Comparisons of the amount of IVIG administered, the incidence of infections, and the use of antimicrobials were performed between the 3 months before ISP and the 3 months after ISP. RESULTS: IVIG administered for HG decreased from 4,902 g in 86 patients before ISP to 1,777 g in 55 patients after ISP, a cost savings of $44,700. Adherence to ISP guidelines was 80%. Compared with before ISP, patients who stopped receiving IVIG after ISP had lower nadir IgG, fewer infections/patient-months, less antimicrobial usage, and a lower hospitalization rate for infection; no deaths occurred. Compared with before ISP, patients receiving IVIG after ISP had lower predose IgG and fewer infections/patient-months; the antibiotic usage, hospitalization rate for infection, and deaths from infection remained stable. CONCLUSION: To our knowledge, this is the first ISP to lead to a dramatic decrease in IVIG usage with high adherence, primarily by selecting out patients at low risk of infection after IVIG discontinuation. Such an ISP is replicable and warrants adoption.

scholarly journals CAR-T in Cancer Treatment: Develop in Self-Optimization, Win-Win in Cooperation

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1955
Author(s):  
Feifei Guo ◽  
Jiuwei Cui
Keyword(s):  
T Cells ◽  
Cancer Treatment ◽  
Unmet Needs ◽  
Hematologic Malignancies ◽  
Limiting Factors ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Car T ◽  
Application Prospects

Despite remarkable achievements in the treatment of hematologic malignancies, chimeric antigen receptor (CAR)-T cell therapy still faces many obstacles. The limited antitumor activity and persistence of infused CAR-T cells, especially in solid tumors, are the main limiting factors for CAR-T therapy. Moreover, clinical security and accessibility are important unmet needs for the application of CAR-T therapy. In view of these challenges, many potentially effective solutions have been proposed and confirmed. Both the independent and combined strategies of CAR-T therapy have exhibited good application prospects. Thus, in this review, we have discussed the cutting-edge breakthroughs in CAR-T therapy for cancer treatment, with the aim of providing a reference for addressing the current challenges.

scholarly journals Hematopoeitic Cell Transplantation and CAR T-Cell Therapy: Complements or Competitors?

2020 ◽  
Vol 10 ◽  
Author(s):  
Scott R. Goldsmith ◽  
Armin Ghobadi ◽  
John F. DiPersio
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematologic Malignancies ◽  
Genetically Engineered ◽  
Cellular Immunotherapy ◽  
T Cell Therapy ◽  
Car T ◽  
History Of ◽  
B Lymphoid

Allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor T cell (CAR T) therapy are the main modalities of adoptive cellular immunotherapy that have widely permeated the clinical space. The advent of both technologies revolutionized treatment of many hematologic malignancies, both offering the chance at sustained remissions for patients who would otherwise invariably succumb to their diseases. The understanding and exploitation of the nonspecific alloreactivity of allo-HCT and the graft-versus-tumor effect is contrasted by the genetically engineered precision of CAR T therapy. Historically, those with relapsed and refractory hematologic malignancies have often been considered for allo-HCT, although outcomes vary dramatically and are associated with potential acute and chronic toxicities. Such patients, mainly with B-lymphoid malignancies, may now be offered CAR T therapy. Yet, a lack of prospective data to guide decisions thereafter requires individualized approaches on whether to proceed to allo-HCT or observe. The continued innovations to make CAR T therapy more effective and accessible will continue to alter such approaches, but similar innovations in allo-HCT will likely result in similarly improved clinical outcomes. In this review, we describe the history of the two platforms, dissect the clinical indications emphasizing their intertwining and competitive roles described in trials and practice guidelines, and highlight innovations in which they complement or inform one another.

scholarly journals Strengthening the CAR-T Cell Therapeutic Application using CRISPR/Cas9 Technology

2021 ◽  
Author(s):  
Muhammad Sadeqi Nezhad ◽  
Mahboubeh Yazdanifar ◽  
Meghdad Abdollahpour-Alitappeh ◽  
Arash Sattari ◽  
Alexander seifalian ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Hematologic Malignancies ◽  
Genetically Engineered ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Promising Tool ◽  
Car T

Adoptive cell immunotherapy with chimeric antigen receptor (CAR) T cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, FDA approved three types of CAR-T cells against CD19 hematologic malignancies, including Tisagenlecleucel (Kymriah), Axicabtagene ciloleucel (Yescarta), and Brexucabtagene autoleucel (Tecartus). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) system has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cell’s anti-tumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be utilized to reduce CAR-T cells toxicity and side effects. Hereby, we discuss the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.

scholarly journals CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges

2018 ◽  
Vol 20 (11) ◽  
pp. 1429-1438 ◽  
Author(s):  
Stephen J Bagley ◽  
Arati S Desai ◽  
Gerald P Linette ◽  
Carl H June ◽  
Donald M O’Rourke
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Hematologic Malignancies ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T-cell therapy for glioblastoma. In addition, despite formidable barriers to T-cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients. In this review, we begin with a discussion of established obstacles to systemic therapy in glioblastoma and how these may be overcome by CAR T cells. We continue with a summary of previously published CAR T-cell trials in GBM, and end by outlining the key therapeutic challenges associated with the use of CAR T cells in this disease.

scholarly journals Evaluating Hematologist's Knowledge of CAR T-Cell Therapy in Hematologic Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2269-2269
Author(s):  
Lauren Willis ◽  
Sara R. Fagerlie ◽  
Sattva S. Neelapu
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Board Of Directors ◽  
Research Funding ◽  
Hematologic Malignancies ◽  
Advisory Committees ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background: The objective of this study was to assess current clinical practices of hematologist/oncologist (hem/onc) specialists related to chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies, in order to identify knowledge, competency, and practice gaps and barriers to optimal care. Methods: A continuing medical education (CME)-certified clinical practice assessment consisting of 25 multiple choice questions was developed to measure knowledge, skills, attitudes, and competence of hem/onc specialists regarding CAR T-cell therapy. The survey instrument was made available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained, and responses were de-identified and aggregated prior to analyses. The activity launched on December 22, 2017 with global distribution, and participant responses are still being collected at the time of abstract submission. Results: At the time of this report there are 192 hem/onc activity participants, collection is on-going. Demographics are listed in Table 1 and levels of confidence and barriers to incorporating CAR T-cell therapy are listed in Table 2.Foundational KnowledgeSub-optimal knowledge was demonstrated in the area of CAR components, dosing, and FDA-approved indications.Over half (61%) could not correctly identify the components of a CAR construct (antigen-specific domain and the signaling domain).Almost half (45%) of the participants did not recognize that currently approved CAR T-cell therapies are dosed as a single infusion.25% demonstrated inaccurate knowledge by recommending patients wait 4 weeks after CAR T-cell infusion before driving.Over half (62%) of participants could not identify the FDA-approved indication for axicabtagene ciloleucel.Knowledge of Clinical Trial DataVery low awareness of efficacy data seen with various CAR T-cell products used to treat R/R B-cell ALL (ELIANA trial), R/R DLBCL (ZUMA-1, JULIET, TRANSCEND trials).Only 32% identified the correct CR/CRi rate seen with tisagenlecleucel in the ELIANA trial.Only 25% correctly identified the CR rate seen with axicabtagene ciloleucel in the ZUMA-1 trial.Only 32% demonstrated knowledge of the 6-month DFS rate for patients in the JULIET trial that had a CR at 3 months.Only 25% identified the association between the dose of JCAR017 and response rates from the TRANSCEND trial.Knowledge and Competence Managing Adverse EventsLack of competence recognizing and treating CAR T-cell associated adverse events such as cytokine release syndrome (CRS) and neurotoxicity.Almost half (44%) could not identify signs of CRS associated with CAR T-cell therapy and 43% lack knowledge that elevated serum C-reactive protein (CRP) is associated with the highest level of CRS (in patients with lymphoma receiving axicabtagene ciloleucel).41% could not identify that the mechanism of tocilizumab is to block IL-6 signaling.Over a third (35%) were unable to identify signs/symptoms/causes of neurotoxicity associated with CAR T-cell therapy.More than half of the learners (54%) could not identify the appropriate role of corticosteroid therapy after CAR T-cell administration in managing CRS and neurotoxicity. Conclusions: This activity found knowledge and competence deficits for hem/onc practitioners related to using CAR T-cell therapy for the treatment of patients with hematologic malignancies. Additionally, the activity demonstrated large gaps in confidence discussing CAR T-cell therapy with patients/families and managing adverse events. There is sub-optimal awareness of CAR T-cell foundational knowledge, clinical trial data, and recognition of common therapy related adverse events and management strategies. Additional education is needed to improve the knowledge, competence, and confidence of academic and community hem/onc specialists who care for patients with hematologic malignancies receiving CAR T-cell therapy as well as strategies for integrating novel agents into clinical practice. Disclosures Neelapu: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Research Funding; Karus: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Unum Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals CAR T cell therapy as a promising approach in cancer immunotherapy: challenges and opportunities

2021 ◽  
Author(s):  
Maryam Akhoundi ◽  
Mahsa Mohammadi ◽  
Seyedeh Saeideh Sahraei ◽  
Mohsen Sheykhhasan ◽  
Nashmin Fayazi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Cell Therapy ◽  
Solid Tumors ◽  
Hematologic Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background Chimeric antigen receptor (CAR)-modified T cell therapy has shown great potential in the immunotherapy of patients with hematologic malignancies. In spite of this striking achievement, there are still major challenges to overcome in CAR T cell therapy of solid tumors, including treatment-related toxicity and specificity. Also, other obstacles may be encountered in tackling solid tumors, such as their immunosuppressive microenvironment, the heterogeneous expression of cell surface markers, and the cumbersome arrival of T cells at the tumor site. Although several strategies have been developed to overcome these challenges, aditional research aimed at enhancing its efficacy with minimum side effects, the design of precise yet simplified work flows and the possibility to scale-up production with reduced costs and related risks is still warranted.Conclusions Here, we review main strategies to establish a balance between the toxicity and activity of CAR T cells in order to enhance their specificity and surpass immunosuppression. In recent years, many clinical studies have been conducted that eventually led to approved products. To date, the FDA has approved two anti-CD19 CAR T cell products for non-Hodgkin lymphoma therapy, i.e., axicbtagene ciloleucel and tisagenlecleucel. With all the advances that have been made in the field of CAR T cell therapy for hematologic malignancies therapy, ongoing studies are focused on optimizing its efficacy and specificity, as well as reducing the side effects. Also, the efforts are poised to broaden CAR T cell therapeutics for other cancers, especially solid tumors.

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