scholarly journals The Financial Impact of Immune Effector Cell Therapy on the Care of Patients with Advanced, B Cell Malignancies

2021 ◽  
Vol 27 (3) ◽  
pp. S311
Author(s):  
Richard T. Maziarz ◽  
Peggy Appel ◽  
Brad Cota ◽  
Jennifer Bishop
Keyword(s):  
Cell Therapy ◽  
B Cell ◽  
Effector Cell ◽  
Financial Impact ◽  
Immune Effector Cell ◽  
B Cell Malignancies ◽  
Immune Effector

scholarly journals Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML)

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3617
Author(s):  
Utkarsh H. Acharya ◽  
Roland B. Walter
Keyword(s):  
Acute Myeloid Leukemia ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Effector Cell ◽  
Antigen Receptor ◽  
Immune Effector Cell ◽  
B Cell Malignancies ◽  
Immune Effector ◽  
Acute Myeloid

Despite the availability of an increasing number of targeted therapeutics and wider use of allogeneic hematopoietic stem cell transplantation, many patients with acute myeloid leukemia (AML) ultimately succumb to this disease. Given their remarkable efficacy in B-acute lymphoblastic leukemia and other CD19-expressing B cell malignancies, there is hope adoptive cellular transfer, particularly chimeric antigen receptor (CAR)-modified immune effector cell (IEC) therapies, may afford a novel, potent immune-based approach for the treatment of AML that complements or replaces existing ones and improves cure rates. However, it is unclear how best to translate the success of these therapies from B cell malignancies, where use of highly potent immunotherapies is facilitated by identified target antigens with near ubiquitous expression on malignant cells and non-fatal consequences from “on-target, off-tumor cell” toxicities. Herein, we review the current status of CAR-modified IEC therapies for AML, with considerations regarding suitable, relatively leukemia-restricted target antigens, expected toxicities, and interactions of the engineered cells with a profoundly immunosuppressive tumor microenvironment that restricts their therapeutic efficacy. With these challenges in mind, we will discuss possible strategies to improve the cells’ potency as well as their therapeutic window for optimal clinical use in AML.

scholarly journals IMMU-07. IMMUNE EFFECTOR CELL ASSOCIATED NEUROTOXICITY (ICANS) AMONG PEDIATRIC AND AYA PATIENTS: MD ANDERSON CANCER CENTER EXPERIENCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii361-iii361
Author(s):  
Brandon Brown ◽  
Paolo Tambaro ◽  
Kris Mahadeo ◽  
Sajad Khazal ◽  
Priti Tewari ◽  
...  
Keyword(s):  
B Cell ◽  
Effector Cell ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Altered Mental Status ◽  
Cancer Center ◽  
Immune Effector Cell ◽  
Immune Effector ◽  
Impaired Ability ◽  
Car T

Abstract INTRODUCTION Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are potentially life-threatening complications associated with immune effector cell (IEC) therapies. We characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. METHODS We reviewed clinical characteristics and severity (based on ASTCT Consensus Criteria) in pediatric and AYA patients with IEC products from 2018–2019 at MDACC. RESULTS Nine patients, median age 15.5 (range: 3–25) years received chimeric antigen receptor (CART) IEC therapy. Four (44%) developed ICANS within median of 8 (range: 3–27) days of CAR T cell infusion and median 6 (range: 2–7) days after CRS. Primary diagnoses were pre-B cell acute lymphoblastic leukemia (8) and mediastinal large B-cell lymphoma (1). Median CRS and ICANS severity grade was 2 (range 1–4). Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was performed in 3 and 1 had background slowing correlating with aphasia. CSF was obtained in two revealing lymphocytosis. All received prophylactic anti-epileptic medication and tocilizumab for concomitant CRS. Three received steroids. CONCLUSION ICANS may present in almost half of pediatric patients within one week of receiving CART products associated with CRS. CAR-T trafficking into the CSF may explain pleocytosis in the CSF. Prospective studies may clarify. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients.

The impact of early versus late tocilizumab administration in patients with cytokine release syndrome secondary to immune effector cell therapy

2021 ◽  
pp. 107815522110526
Author(s):  
Rachel Peaytt ◽  
Laura Beth Parsons ◽  
Darby Siler ◽  
Rachel Matthews ◽  
Belinda Li ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Interleukin 6 ◽  
Effector Cell ◽  
Negative Consequences ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Effector Cell ◽  
Immune Effector ◽  
Fever Onset ◽  
The Impact

Introduction Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity. Optimizing the timing of tocilizumab could avoid glucocorticoid use and improve outcomes. This study assesses tocilizumab timing on patient outcomes and healthcare resource utilization. Methods This is a retrospective single-institution analysis of 28 patients who received tocilizumab for cytokine release syndrome secondary to immune effector cell therapy. Patients were categorized into two groups: Early Tocilizumab (within 24 h) or Late Tocilizumab groups (more than 24 h) from fever onset. The composite primary endpoint was glucocorticoid use, intensive care unit admission, or inpatient mortality. Secondary outcomes include comparing the various presentations of cytokine release syndrome, need for vasopressors, length of stay, rates of neurotoxicity, and C-reactive protein and ferritin trends. Results The Early Tocilizumab group presented with more rapid fever onset (35 vs.113 h, P = 0.017) and higher maximum cytokine release syndrome grade (Median, Grade 2 vs. Grade 1, P = 0.025). Additionally, the Early Tocilizumab group required more doses of tocilizumab (Median, 2 vs. 1, P = 0.037). Despite the difference in cytokine release syndrome presentation, the primary composite endpoint was not statistically different between groups. Conclusion Earlier onset of fever appears to be associated with more severe, progressive cytokine release syndrome requiring multiple doses of anti-interleukin-6 therapy. Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome.

scholarly journals IMMU-52. IMMUNE EFFECTOR CELL ASSOCIATED NEUROTOXICITY (ICANS) AMONG PEDIATRIC AND AYA PATIENTS: MD ANDERSON CANCER CENTER EXPERIENCE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii116-ii116
Author(s):  
Brandon Brown ◽  
Kris Mahadeo ◽  
Sajad Khazal ◽  
Demetrios Petropoulos ◽  
Priti Tewari ◽  
...  
Keyword(s):  
B Cell ◽  
Effector Cell ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Altered Mental Status ◽  
Cancer Center ◽  
Immune Effector Cell ◽  
Immune Effector ◽  
Impaired Ability ◽  
Car T

Abstract INTRODUCTION Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are potentially life-threatening complications associated with immune effector cell (IEC) therapies. We characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. METHODS We reviewed clinical characteristics and severity (based on ASTCT Consensus Criteria) in pediatric and AYA patients who received IEC products from 2018–2019 at MDACC. RESULTS Nine patients, median age 15.5 (range: 3–25) years received chimeric antigen receptor (CART) IEC therapy. Four (44%) developed ICANS within median of 8 (range: 3–27) days of CAR T cell infusion and median 6 (range: 2–7) days after CRS. Primary diagnoses were pre-B cell acute lymphoblastic leukemia (8) and mediastinal large B-cell lymphoma (1). Median CRS and ICANS severity grade was 2 (range 1–4). Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was performed in 3 and 1 had background slowing correlating with aphasia. CSF was obtained in two revealing lymphocytosis. All received prophylactic anti-epileptic medication and tocilizumab for concomitant CRS. Three received steroids. CONCLUSION ICANS may present in almost half of pediatric patients within one week of receiving CART products associated with CRS. CAR-T trafficking into the CSF may explain pleocytosis in the CSF. Prospective studies may clarify. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients.

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