A review of CD19-targeted immunotherapies for relapsed or refractory acute lymphoblastic leukemia

Abstract

Aim Novel immunotherapies have generated high response rates and unique adverse effects among patients with relapsed or refractory acute lymphoblastic leukemia. Therapies engaging endogenous T-cells against acute lymphoblastic leukemia are emerging for children and adults with various poor prognostic factors, thus accurate knowledge of immunotherapies is necessary for their effective implementation in the future. In this review, we evaluate clinical trial data regarding chimeric antigen receptor T-cells and blinatumomab, for the treatment of relapsed or refractory acute lymphoblastic leukemia. Summary In the relapsed or refractory setting, response rates rapidly diminish after subsequent lines of chemotherapy and cumulative toxicities may cause significant patient harm. Immunotherapies provide an approach to improve response rates and minimize traditional toxicities via novel mechanisms of action. Two therapies targeting CD19 antigens expressed on B-cell acute lymphoblastic leukemia lineages, chimeric antigen receptor T-cells, and blinatumomab have induced complete remissions among high-risk patient populations, especially those refractory to multiple therapies. Adverse effects such as cytokine release syndrome and neurologic sequelae remain serious precautions of each therapy. Conclusion Knowledge of immunotherapy mechanisms and clinical outcomes associated with immunotherapies is critical for the optimization of treating patients with relapsed or refractory acute lymphoblastic leukemia. Future use of chimeric antigen receptor T-cells and blinatumomab demands proper assessment of a patient's disease and treatment history in addition to unique monitoring and supportive care interventions.

Biophysical Characterization of the Leukemic Bone Marrow Vasculature Reveals Benefits of Neoadjuvant Low-Dose Radiation Therapy

“…Increased K trans values in low to moderate ALL burden may indicate a therapeutic window of enhanced delivery for ALL antibody therapies, such as those targeting CD19 or CD22, which are similar in size to 150KDa dextran. 39,40 However, differences in vascular transport mechanisms of dextran and therapeutic antibodies make further assessments of antibody delivery kinetics necessary. 41 In contrast to 150kDa dextran, small molecular agents such as Hoechst dye and daunorubicin are able to easily cross the vessel wall of both healthy and ALL-burdened BMV.…”

Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients

“…In clinical trials, the second-generation CAR constructs are most commonly used for CAR-T therapy. The processes of CAR-T therapy can be simplified as: obtaining autologous T cells by leukapheresis; selection of cytotoxic T cells; transduction using viral vector; replication and extension of CAR-T cells; conditioning chemotherapy; CAR-T cell infusion 24 . In this current study, lentiviral vector instead of retrovirus was used for transduction due to its stability, wide spectrum of infection, and less carcinogenicity.…”

Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL)

“…A particular attention should be put on central venous lines management, and clinicians should be alert for the risk of catheter-related infections. Immunoglobulin level monitoring and supplementation in case of low IgG concentration is recommended, particularly in patients with a history of serious infections [12].…”