Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia that carries poor prognosis in adults especially in the setting of high risk cytogenetics and relapsed/refractory (R/R) disease. Advancements in immunotherapy have led to the development of several monoclonal antibodies (MoAbs) and chimeric antigen receptor (CAR) T cells that are capable of targeting certain surface antigens on leukemic cells, resulting in their destruction. Areas covered: This article reviews the mechanism of action, outcomes of various trials, and adverse effects of MoAbs and CAR-T cells used in the treatment of precursor B-cell ALL. Expert commentary: Some of the immunotherapeutic agents that have been approved for the treatment of R/R precursor B-cell ALL have shown superior efficacy and safety profile compared to chemotherapy in advanced disease. Several trials are now being conducted to evaluate the role of certain MoAbs in combination with chemotherapy in the treatment of B-cell ALL. Additionally, their use in the frontline setting with more favorable host characteristics may also result in superior outcomes compared to the current standard of care.

Metabolic underpinnings of leukemia pathology and treatment

“…ALL is a heterogeneous disease marked by reprogrammed metabolism and atypical molecular signaling and, like CML, can be induced by the presence of the Philadelphia chromosome and expression of Bcr‐Abl, particularly in adult patients. We will focus here on the most recent investigations of ALL cell metabolism as fuller pictures of ALL subtypes are recently and individually reviewed (B‐ALL; T‐ALL).…”

“…85 For adults, remission is achieved in 85% of patients but 5-year survival is onlỹ 40% 86 and decreases to 7% if a relapse occurs. 87 89,90 ; T-ALL [91][92][93] ).…”

Terapia genética com células CAR-T para leucemia linfocítica aguda

“…As principais complicações pelo uso desta nova terapia incluíram a elevada taxa de recidiva de LLA e sintomatologia característica da "Síndrome de liberação de citocinas", incluindo hipotensão, febre, alterações neurológicas e hipóxia (TANG et al, 2016;TURTLE et al, 2016;VALECHA et al, 2017). Assim, a intervenção terapêutica em pacientes com LLA mediante uso de células CAR-T dos estudos clínicos analisados mostrou-se promissora, melhorando o prognóstico dos pacientes.…”

Gene therapy as advanced technology for the treatment of Leukemia: CAR-T therapy

“…The Tisagenlecleucel is having a boxed warning for CRS that is a response which can activate the proliferation of CAR-T cells leading to high fever and flu like symptoms. To treat the severe CRS, FDA has approved Tocilizumab, which is commonly known as Actemra in patients aged 2 year or above (Valecha et al, 2017). The approval of tocilizumab was based on the treatment of the 69% patients from CRS within 2 weeks by giving 1 or 2 doses of drug.…”