Pharmacotherapeutic management of T-cell acute lymphoblastic leukemia in adults: an update of the literature

ABSTRACT

Introduction

T-cell acute lymphoblastic leukemia (T-ALL) is a rare but potentially life-threatening heterogeneous hematologic malignancy that requires prompt diagnosis and treatment by hematologists. So far, therapeutic advances have been achieved in the management of this disease mainly by adopting pediatric-like regimens, and cure rates are significantly worse than in childhood. In T-ALL, less than 70% of adults achieve long-term survival. The prognosis after relapse is still very poor. Hence, there is urgent need to improve therapy of T-ALL by testing new compounds and combinations for the treatment of this disease.

Areas covered

This review provides a comprehensive update on the most recent treatment approaches in adults with de novo and relapsed/refractory adult T-ALL.

Expert opinion

Intensifying chemotherapy may reduce the incidence of recurrent disease in adult patients, but it has not come without a cost. Novel agents with selective T-ALL activity (e.g. nelarabine) may improve survival in some patient subsets. Due to modern genomic and transcriptomic techniques, various novel potential targets might change the treatment landscape in the next few years and will, hopefully alongside with cellular therapies, augment the therapeutic armamentarium in the near future.

KEYWORDS:

• Acute lymphoblastic leukemia
• allogeneic stem cell transplantation
• nelarabine
• measurable residual disease

Article highlights

•T-ALL is a heterogenous disease - both clinically and biologically.

•Pediatric-inspired treatment approaches are key elements of therapy in first line treatment.

•MRD monitoring has become indispensable and treatment allocation towards stem cell transplantation is usually directed by MRD response.

•In case of relapse, treatment options beyond conventional chemotherapy are limited with nelarabine being the only T-cell specific agent approved.

•Based upon recent progress unraveling the molecular background of T-ALL new compounds have raised on the horizon, currently being tested in several preclinical and clinical trials.

•Progress in solving problems with CAR-T-cell therapy represents another exciting treatment option.

This box summarizes key points contained in the article.

Declaration of interest

A Viardot has served on advisory boards and received honoraria from Kite/Gilead Sciences, Bristol-Myers Squibb, Novartis, Amgen Inc and Roche while E Sala has served on the advisory boards of and received honoraria from Novartis, Kite/Gilead Sciences, Jazz Pharmaceuticals and Bristol-Myers Squibb. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This article was not funded.