Targeted therapy paves the way for the cure of acute lymphoblastic leukaemia

Abstract

The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T-cell therapy. A number of new therapies have been approved by the US Food and Drug Administration in the past 5 years, including blinatumomab in 2014, inotuzumab ozagamicin in 2017 and tisagenlecleucel in 2017 for relapsed/refractory ALL. This has led to tremendous improvement in long-term survival, of more than 50% in patients with precursor B-ALL [50-70% in patients with Philadelphia chromosome (Ph)-positive ALL)], 50-60% in T-ALL and 80% in mature B-ALL. Research is ongoing to optimize the benefit of targeted therapeutics with the goal of decreasing the use of cytotoxic therapies.

CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies

“…The preliminary results observed in the first 10 patients led to the extension of the trial to include 54 patients in total, most of them diagnosed with ALL. An important caveat is that our study included both pediatric and adult patients with ALL, which are known to have a different prognosis, 16 and this complicates the comparison with other studies. Other important differences are that (1) 87% of our patients with ALL had already received an alloHCT, compared to 33%-62% in other studies; 11,[17][18][19][20][21] and (2) response evaluation was performed at day +100, 4-10 weeks later than in other studies.…”

Neonatal Acute Lymphoblastic Leukemia with t(9;11) Translocation Presenting as Blueberry Muffin Baby: Successful Treatment by ALL-BFM Induction Therapy, Allogeneic Stem Cell Transplantation from an Unrelated Donor, and PCR-MRD-Guided Post-Transplant Follow-Up

“…A similar strategy was pursued during the post-transplant period with PCR-based measurement of MRD in sequential bone marrow specimens obtained every 6-8 weeks. Regular monitoring allowed early intervention with bispecific antibodies [ 19 ] or conjugated antibodies [ 20 , 21 ] should MRD increase during serial follow-up. The patient has remained MRD-negative and is alive and well at age 2 years.…”

Polycationic peptide R7-G-Aβ25-35 selectively induces cell death in leukemia Jurkat T cells through speedy mitochondrial depolarization, and CASPASE-3 -independent mechanism

“…Although conventional cytotoxic chemotherapy [ 5 , 6 ] or in combination with monoclonal antibodies (e.g., Ref. [ 7 ]) used to treat ALL results in high cure rates, treatment is suboptimal in an important percentage of pediatric and adult patients with relapsed and refractory ALL. Therefore, new treatment options are needed for the treatment of resistance ALL.…”