Treatment of Adult T-Cell Leukemia/Lymphoma: Established Paradigms and Emerging Directions

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a rare, aggressive subtype of peripheral T-cell lymphoma developing after many years of chronic, asymptomatic infection with the retrovirus human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 is endemic to certain geographic areas of the world, and primary infection generally occurs in infancy through mother-to-child transmission via breastfeeding. In less than 5% of infected individuals, a decades-long pathogenic process culminates in the development of ATL. Aggressive subtypes of ATL are life-threatening and challenging to treat, with median overall survival typically less than 1 year in the absence of allogeneic hematopoietic cell transplantation (alloHCT). Owing to the rarity of this illness, prospective large-scale clinical trials have been challenging to perform, and treatment recommendations are largely founded upon limited evidence. Herein, we review the current therapeutic options for ATL, providing a broad literature overview of the foremost clinical trials and reports of this disease. We emphasize our own treatment paradigm, which is broadly based upon disease subtype, patient fitness, and intent to perform alloHCT. Finally, we highlight recent advances in understanding ATL disease biology and important ongoing clinical trials that we foresee as informative and potentially practice-changing.

Keywords: Adult T-cell leukemia/lymphoma; Human T-cell lymphotropic virus; Mogamulizumab; Peripheral T-cell lymphoma.

Figure 1.. Schematic Representation.

Human T-cell lymphotropic virus type 1 (HTLV1) exists with high prevalence in various geographical regions, most notably Japan, the Caribbean islands, sub-Saharan Africa, South America, and regions of Oceania. The virus is predominantly spread mother-to-child through breastfeeding and infects CD4+ T cells. In less than 5% of infected individuals, a multihit pathogenic process occurs over decades as multiple somatic mutations occur, eventually resulting in an HTLV-1 associated peripheral T-cell lymphoma known as adult T-cell leukemia/lymphoma (ATL). ATL has varied manifestations and subtypes (see text). Created in BioRender.com.