scholarly journals Relapsed ALL: CAR T vs transplant vs novel therapies

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 1-6
Author(s):  
Noelle V. Frey
Keyword(s):  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Disease Characteristics ◽  
Car T ◽  
Life Threatening ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Improve Rate

Abstract Chimeric antigen receptor T-cell therapy targeting CD19 (CART19) has expanded the treatment options for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). The approval of tisagenlecleucel for pediatric and young adult patients with r/r ALL has allowed broader access for some patients, but the treatment of older adults is available (at the time of this writing) only within a clinical trial. High remission rates have been consistently observed with varied CART19 products and treatment platforms, but durability of remissions and thus the potential role of a consolidative allogeneic stem cell transplant (SCT) is more uncertain and likely to vary by product and population treated. The immunologic characteristics of CARTs that confer high response rates also account for the life-threatening toxicities of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, the severity of which also varies by patient and disease characteristics and product. Further considerations informing a decision to treat include feasibility of leukapheresis and timeline of manufacture, alternative treatment options available, and the appropriateness of a potential consolidative allogeneic SCT. Advances in the field are under way to improve rate and duration of responses and to mitigate toxicity.

scholarly journals Management of toxicities associated with novel immunotherapy agents in acute lymphoblastic leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062071989989 ◽  
Author(s):  
Tania Jain ◽  
Mark R. Litzow
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Sinusoidal Obstruction Syndrome ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Therapeutic Landscape ◽  
Car T Cell Therapy ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

The advent of novel immunotherapies, such as blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T cell therapy, has revolutionized the therapeutic landscape in the treatment of relapsed/refractory B cell acute lymphoblastic leukemia, but can be associated with specific toxicities. We review unique toxicities of each of these in this article. Blinatumomab, a bispecific T cell engager, has been associated with cytokine release syndrome (CRS) and neurological toxicities, both of which can be prevented and managed with corticosteroids. Inotuzumab is a calicheamicin-conjugated CD22 targeting antibody. The calicheamicin component of the drug is likely associated with the hepatotoxicity seen with inotuzumab, especially sinusoidal obstruction syndrome, which can happen both in the context of the drug alone, and also with allogeneic stem cell transplantation. QT prolongation has also been noted with inotuzumab. CAR T therapy uses genetically modified autologous T cells directed against CD19, a known target on B cells. CRS and neurological symptoms, formally termed as immune-effector-cell-associated neurological syndrome, have been described along with hypogammaglobulinemia, cytopenias, and infections.

scholarly journals How to Combine the Two Landmark Treatment Methods—Allogeneic Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Together to Cure High-Risk B Cell Acute Lymphoblastic Leukemia?

2020 ◽  
Vol 11 ◽  
Author(s):  
Mingming Zhang ◽  
He Huang
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Lymphoblastic Leukemia ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has made tremendous progress in the last few decades and is increasingly being used worldwide. The success of haploidentical HSCT has made it possible to have “a donor for everyone”. Patients who received transplantation in remission may have a favorable outcome, while those who were transplanted in advanced stages of disease have a poor prognosis. Although chimeric antigen receptor T (CAR-T) cell therapy is currently a milestone in the immunotherapy of relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL) and has demonstrated high remission rates in patients previously treated in multiple lines, the relatively high relapse rate remains a barrier to CAR-T cell therapy becoming an excellent cure option. Therefore, combining these two approaches (allo-HSCT and CAR-T cell therapy) is an attractive area of research to further improve the prognosis of R/R B-ALL. In this review, we will discuss the current clinical practices of combining allo-HSCT with CAR-T cell therapy based on available data, including CAR-T cells as a bridge to allo-HSCT for R/R B-ALL and CAR-T cell infusion for post-transplant relapse. We will further explore not only other possible ways to combine the two approaches, including CAR-T cell therapy to clear minimal residual disease peri-transplantation and incorporation of CAR technology to treat graft-versus-host disease, but also the potential of CAR-T cells as a part of allo-HSCT.

scholarly journals Reactions Related to CAR-T Cell Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Lele Miao ◽  
Zhengchao Zhang ◽  
Zhijian Ren ◽  
Yumin Li
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adverse Reactions ◽  
Tumor Lysis Syndrome ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Life Threatening

The application of chimeric antigen receptor (CAR) T-cell therapy as a tumor immunotherapy has received great interest in recent years. This therapeutic approach has been used to treat hematological malignancies solid tumors. However, it is associated with adverse reactions such as, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), off-target effects, anaphylaxis, infections associated with CAR-T-cell infusion (CTI), tumor lysis syndrome (TLS), B-cell dysplasia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) and coagulation disorders. These adverse reactions can be life-threatening, and thus they should be identified early and treated effectively. In this paper, we review the adverse reactions associated with CAR-T cells, the mechanisms driving such adverse reactions, and strategies to subvert them. This review will provide important reference data to guide clinical application of CAR-T cell therapy.

scholarly journals Expanding the Role of CAR-T Cell Therapy to Systemic Lupus Erythematosus

2020 ◽  
pp. 105-112
Author(s):  
Shreya Patel ◽  
Kelly Brassil ◽  
Paiboon Jungsuwadee
Keyword(s):  
T Cell ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Current Treatment ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder resulting from autoantibodies produced by B-cell derived plasma cells. Clinical presentation ranges from mild skin rash to multiorgan failure. Regardless of the clinical presentation or severity of the disease, patients with SLE often require life-long treatment. Current treatment recommendations for SLE include hydroxychloroquine, glucocorticoids, immunomodulatory agents, cyclophosphamide, and biologic agents. Despite availability of these agents, the condition of some patients with SLE progressively worsens. With limited treatment options, new and novel therapeutic approaches are needed. Given the active role of B cells in the pathophysiology of SLE, they present an attractive target for therapies evolving in the oncology field. Amongst these, immune effector cell therapies, including chimeric antigen receptor (CAR)-T cell therapy, have proven beneficial in targeting B cells. The eradication of B cells, along with the potential for T cell persistence, has resulted in prolonged remission or stable disease. This review provides an overview of the pathophysiology of SLE; current treatment options, including monoclonal antibodies targeting cluster of differentiation-20 (CD20), CD22, and B cell-activating factor (BAFF); and explores why and how immune effector cell therapies may prove a promising therapeutic option for this patient population, particularly for individuals with refractory disease. Clinical implications from currently approved U.S. Food and Drug Administration (FDA) agents for haematologic malignancies are discussed and provide insight into considerations for applying this therapy to the patient population with SLE in the context of clinical trials.

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