Acute lymphoblastic leukemia in young adults: which up-front treatment?

Abstract

Significant improvements have occurred for adolescent and young adult (AYA) B-cell acute lymphoblastic leukemia (B-ALL) patients following the widespread adoption of "pediatric-inspired" treatment regimens for AYA patients cared for in adult oncology settings. However, for AYA patients, aged 15 to 39, an outcomes gap remains in B-ALL, necessitating the incorporation of novel therapies into up-front treatment regimens. As a result, clinical trial enrollment remains the current standard of care for AYA B-ALL across disease subtypes when available and accessible. Currently, several up-front trials are looking to incorporate the use of inotuzumab, blinatumomab, and chimeric antigen receptor T-cell therapy into existing chemotherapy backbones for AYA patients, as well as tyrosine kinase inhibitors for both Philadelphia-positive (Ph+) and Ph-like B-ALL. In addition to ongoing attempts to improve up-front treatments by incorporating immunotherapy and targeted approaches, the increased use of next generation sequencing for measurable residual disease evaluation has led to superior risk-stratification and a decreased need to pursue consolidative hematopoietic stem cell transplantation during the first complete remission for many patients.

Graphical abstract

Figure 1.

Up-front AYA B-ALL treatment schemas. Ara-C, cytarabine; CNS3, central nervous system; CPM, cyclophosphamide; cXRT, cranial radiation; DEX, dexamethasone; DNR, daunorubicin; DOX, doxorubicin; HD-MTX, high-dose methotrexate; IT-MTX, intrathecal methotrexate; IT-Arac, intrathecal cytarabine; PEG, pegaspargase; PO-MTX, oral methotrexate; Pred, prednisone; 6-MP, mercaptopurine; 6-TG, thioguanine; VCR, vincristine.

Figure 2.

Time line of treatment approvals in B-ALL. Brexu-cel, brexucabtagene autoleucel; Car, chimeric antigen receptor; MRD, measurable residual disease; Ph-neg, Philadelphia negative; R/R, relapsed/refractory; Tisa-cel, tisagenlecleucel.