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Is CAR T-cell therapy a boon for acute lymphoblastic leukemia patients??


Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most prevalent cancer subtype among all the leukemias that occur in children. It has a poor prognosis and is the major cause of cancer-related death, particularly in children. All cases of ALL do not subside completely with the treatment, and a few cases may recur. This condition is called relapse or refractory R/R ALL. It might occur months or even years later, and it is seen in around 15–20% of total ALL cases. The treatment of Relapsed ALL is challenging. Chemotherapy, radiation therapy, stem cell (bone marrow) transplants, immunotherapy, targeted therapy, or a combination of treatments can all be considered as potential treatment options for R/R ALL.


What is the significance of car t-cell therapy in all?


  • The majority of patients with relapsed/refractory acute (R/R) lymphoblastic leukemia (ALL) continue to have an inoperable disease despite currently available treatments.

  • According to the literature, depending on the age of the patient, the type of salvage therapy used, and the patient's response, R/R ALL is linked with a complete response rate (CRR) of between 30 and 45% and a median overall survival (OS) of between 4 and 8 months[1].

  • Patients who show relapse following allogenic hematopoietic cell transplantation (alloHCT) have an extremely poor prognosis. The response rate in this patient population has increased with the use of novel medications such as inotuzumab ozogamicin (IO), or blinatumomab, but responses are typically short-lived.

  • For this patient population, chimeric antigen receptor (CAR) T-cell treatment has opened up new therapeutic options and produced outstanding clinical results[2].


What is car t-cell therapy and ARI-0001?


  • Antibody-targeted treatments that target the cell surface antigens CD19, CD20, and CD22 that play an important role in the pathogenesis of ALL have made significant progress in recent years.

  • One such targeted treatment for treating B-cell cancers is adoptive cell therapy, which uses T-cells that have been genetically modified to express chimeric antigen receptors (CAR) that target CD19. In particular, CAR-T cells that specifically target thisCD19 have produced complete response (CR) rates in patients with ALL[3].

  • The Spanish Agency of Medicines and Medical Devices (AEMPS) granted authorization to an advanced therapy medicinal product called ARI-0001 (varnimcabtagene-autoleucel)that was created at the Hospital Clinic de Barcelona (Spain), in February 2021. It is being used for the treatment of patients older than 25 years with relapsed/refractory (RR) acute lymphoblastic leukemia (ALL). This drug also received priority medicine designation from EMA(European Medicines Agency).

  • In this ARI-0001, same patient T-cells are transformed into aCD137-based second generation CAR agent to target CD19 specifically[4].


What is the clinical efficacy of ARI-0001 in treating all?


  • A phase III clinical trial was conductedto evaluate the safety of infusion of ARI-0001 cells on patients with leukemia or lymphomaCD19 + that is resistant or refractory to treatment and with a prognosis of less than two years(Clinical trials identifier - NCT03144583).In this trial, out of nine patients who received treatment, seven (87.5%) of them responded to it. The trial concluded that the use of ARI-0001 cell treatment in patients with high-risk CLL proved practical, secure, and successful.

  • Another phase III trial was conducted where patients with CD19+ acute lymphoid leukemia resistant or refractory to therapy received an infusion of ARI-0001 cells (CART19-BE-02)(Clinical trials identifier - NCT04778579). The results indicated that this drug is safe and efficient in R/R ALL.


All about car t-cell therapy in all!


Patients with R/R B-ALL may experience long-term advantages from CAR T-cell therapy. However, patient outcomes and the likelihood of relapse were significantly influenced by the patient's disease status at the time of infusion. The overall effectiveness of CAR T-cell therapy can be increased by conducting well controlled studies and better reporting. With these efforts, it should be possible to give CAR T-cells that can improve patient survival, have a lower incidence of side effects, and ultimately result in lower treatment costs for patients.


References


1. L. Schultz, Chimeric Antigen Receptor T Cell Therapy for Pediatric B-ALL: Narrowing the Gap Between Early and Long-Term Outcomes,”Front Immunol, vol. 11, p. 1985, 2020, doi: 10.3389/fimmu.2020.01985.

2. V. Ortíz-Maldonado et al., CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies,”Mol Ther, vol. 29, no. 2, pp. 636–644, Feb. 2021, doi: 10.1016/j.ymthe.2020.09.027.

3. S. Aamir, M. Y. Anwar, F. Khalid, S. I. Khan, M. A. Ali, and Z. E. Khattak, Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes,”Clin Lymphoma Myeloma Leuk, vol. 21, no. 4, pp. e334–e347, Apr. 2021, doi: 10.1016/j.clml.2020.12.010.

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Collaborators

IIT Guwahati
University of Manchester
Rhenix Lifesciences
American university of Sharjah
IIT Delhi
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