Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia

ABSTRACT

Introduction: Cellular immunotherapy with autologous or allogeneic T cells, genetically engineered to express chimeric antigen receptors (CARs) or T-cell receptors, in order to redirect their cytotoxic specificity toward malignant cells, is emerging as a promising new treatment modality. The most advanced approach in clinical development is the use of anti-CD19 CAR T-cells for the treatment of CD19⁺ B-cell malignancies, including acute lymphocytic leukemia (ALL).

Areas covered: Recently, the Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell product, tisagenlecleucel, for the treatment of pediatric and young adult patients with relapsed/refractory ALL. In this overview, we described the advances in the field, including a summary of clinical trials with tisagenlecleucel in ALL published to date.

Expert opinion: CAR T-cell therapy has been developed in the context of small clinical studies and very few centers have had to deal with the challenges of managing CAR T-cells administration. However, this approach is likely to become a standard option for patients with relapsed/refractory B-cell lineage ALL.

KEYWORDS:

• Acute lymphoblastic leukemia
• CAR T-cells
• CD19-directed CARs
• cytokine release syndrome
• prognosis
• relapse

Box 1. Drug summary box.

Article highlights box

• CAR T-cell therapy is a very promising approach for the treatment of R/R B-cell lineage ALL.

• The phase 2 ELIANA trial has recently shown a 83% response rate with durable remissions.

• CAR T-cell therapy is however associated with acute toxicities that require intensive and accurate monitoring and management.

• Based on these results, FDA has recently approved tisagenlecleucel (CTL-019) for the treatment of R/R pediatric and young adult patients with B-cell lineage ALL.

Acknowledgments

We greatly thank Professor Charles Dumontet for re-reading the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.