Acute Lymphoblastic Leukemia: Treatment

Acute Lymphoblastic Leukemia: overview

This algorithm organizes treatment of acute lymphoblastic leukemia by Philadelphia chromosome status, lineage and line of therapy. For Ph-positive (BCR::ABL1) ALL, the chart shows a TKI plus chemotherapy, supported by PhALLCON, in which ponatinib with reduced-intensity chemotherapy produced a higher MRD-negative complete remission rate than imatinib. The chemotherapy-sparing alternative is a TKI plus blinatumomab (D-ALBA). For Ph-negative B-cell ALL, adolescents and young adults receive pediatric-inspired chemotherapy (CALGB 10403), and blinatumomab is added for MRD-positive disease (BLAST). T-cell ALL is treated with multiagent chemotherapy with or without nelarabine.

For relapsed or refractory B-ALL, the options are blinatumomab (TOWER), inotuzumab ozogamicin (INO-VATE) and CD19 CAR-T therapy (tisagenlecleucel or brexucabtagene autoleucel). In the site's INO-VATE summary, inotuzumab ozogamicin achieved higher complete remission and MRD-negativity rates than salvage chemotherapy in CD22-positive disease and allowed more patients to bridge to allogeneic transplant, with veno-occlusive disease as an important post-transplant complication.

Trials behind this algorithm

• PhALLCON Jabbour E et al, JAMA, 2024; PMID: 38722621
• D-ALBA (GIMEMA LAL2116) Foà R et al, NEJM, 2020; PMID: 33085860
• CALGB 10403 Stock W et al, Blood, 2019; PMID: 30658992
• TOWER, Blinatumab TRIAL Kantarjian et al., NEJM, 2017, PMID: 28249141
• INO-VATE Kantarjian H et al, NEJM, 2016; PMID: 27332584

Background reading: Acute lymphoblastic leukemia (ALL) board review notes.