![]() In the last few years, the advent of novel targeted immunotherapies, specifically blinatumomab, inotuzumab, and chimeric antigen receptor T cells (CAR-T cells), has changed the therapeutic landscape of R/R B-cell precursor ALL (BCP-ALL). Relapsed or refractory (R/R) ALL is still a major concern, with a dismal prognosis in both children and adults and with an overall survival of 3 to 12 months depending on the duration of the first remission and the number of lines of salvage therapy. Despite these significant advances in treatment, less than 50% of adult patients survive 5 years or more, and about 15–20% of children suffer a relapse. Remarkable advances have been achieved in the treatment of ALL thanks to the optimal use of intensive chemotherapy, the implementation of minimal residual disease monitoring, and better supportive care, allowing most pediatric and adult patients to achieve a complete hematologic remission (CR). This disease represents the most frequent cancer in the pediatric population, especially in infants aged 1–4 years, with a subsequent decrease in the overall incidence which reaches its lowest point in young adults aged 25–45 years. The present review examined the evidence for an appropriate use of the new immunotherapies in ALL patients and provided some appraisal of the current and future possible uses of these drugs for achieving further therapeutic improvement in the treatment of this disease.Īcute lymphoblastic leukemia (ALL) is a hematologic malignancy that originates from the proliferation of a single B- or T-lymphocyte progenitor, which proliferates and accumulates in the blood the bone marrow and, possibly, the extramedullary sites. The results from these studies have led to the development of potentially curative treatment modalities, even for older ALL patients who cannot be treated with conventional intensive chemotherapy. In Ph-positive ALL, reproducible results are showing that frontline treatment programs, based on the combination of tyrosine kinase inhibitors and immunotherapy, can achieve unprecedented rates of hematologic and molecular remission as well as a long-term cure, even in the absence of chemotherapy and alloHSCT. The preliminary data suggest that this approach may increase the cure rate and perhaps reduce the use of allogeneic stem cell transplantation (alloHSCT) in first remission. In addition, with the aim of increasing the rate and depth of molecular remission, clinical studies are currently evaluating the combination of these immunotherapies with chemotherapy in the contest of frontline treatment. ![]() ![]() Therefore, how to optimize the choice and the timing of such new treatments within different clinical settings remains a matter of debate. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated with a remarkably poor clinical outcome. Novel immune therapies are currently being used for patients with R/R ALL based on their ability to induce not only hematologic but also molecular remission.
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