Catalin Danaı̈la

Background. Therapy for acute lymphoblastic leukemia (ALL) are currently initially efficient, but even if a high percentage of patients have an initial complete remission (CR), most of them relapse. Recent data shows that immunotherapy with either bispecific T-cell engagers (BiTEs) of chimeric antigen receptor (CAR) T cells can eliminate residual chemotherapy-resistant B-ALL cells. Objective. The objective of the manuscript is to present improvements in the clinical outcome for chemotherapy-resistant ALL in the real-life setting. Methods. We present the role of novel therapies for relapsed B-cell ALL, including the drugs under investigation in phase I-III clinical trials, as a potential bridge to transplant. Blinatumomab is presented in a critical review, presenting both the advantages of this drug, as well as its limitations. Results. Bispecific antibodies are discussed, describing the clinical trials that resulted in its approval by the FDA and EMA. The real-life setting for relapsed B-cell ALL is described. Conclusion. In the current manuscript, we present blinatumomab as a therapeutic alternative in the bridge-to-transplant setting for refractory or relapsed ALL, to gain a better understanding of the available therapies and evidence-based data for these patients in 2020.

Acute myeloid leukemia (AML) is generally considered a poorly immunogenic malignancy, displaying a “non-inflamed” leukemia microenvironment, leading to T cell tolerance. However, the immune landscape of AML is much more heterogeneous. Since B7 expression is regarded as a consequence of an interferon-mediated “inflammatory” phenotype, we have investigated by flow cytometry the B7 checkpoint ligands B7.1, B7.2, PD-L1, PD-L2, ICOS-L, B7-H3, B7-H4 on the AML blasts of 30 newly diagnosed patients, and their corresponding receptors (CTLA-4, PD-1 and ICOS) on bone marrow T cell maturation populations. We could thus evidence B7 negative and B7 positive leukemias, either with an isolated expression, or part of eight different checkpoint ligand “signatures” that always included an inhibitory B7 molecule. B7 positive AMLs encompassed intermediate and adverse ELN risk cases and displayed mainly central memory CD4+ T cells with high ICOS levels, and effector CD8+ T cells with high PD-1 expression. B7 negative cases were rather classified as AML with recurrent genetic anomalies and displayed predominantly naïve T cells, with the exception of NPM1 mutated AMLs, which expressed B7-H3. These different B7 immune profiles suggest that specific immunotherapies are required to target the distinct immune evasion strategies of this genetically heterogeneous disease.