Optimal Use of Novel Immunotherapeutics in B-Cell Precursor ALL

Simple Summary In this review, we discussed the impact of novel immune therapies on the treatment of child and adult acute lymphoblastic leukemia (ALL). Based on the promising results achieved in the relapsed/refractory (R/R) setting, several trials are currently evaluating the clinical benefit of incorporating these new drugs into frontline treatments. The results emerging from the most recent studies are opening new avenues to further the significant improvements in the clinical outcome of this disease. 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. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated with a remarkably poor clinical outcome. Therefore, how to optimize the choice and the timing of such new treatments within different clinical settings remains a matter of debate. 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. 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 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 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. 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.

Automated summary

In this review, the impact of novel immune therapies on the treatment of acute lymphoblastic leukemia (ALL) in children and adults was discussed. Results from trials evaluating the incorporation of these new drugs into frontline treatments show promising clinical benefit. Clinical conditions, such as high tumor burden or extra medullary relapse, still have poor clinical outcome despite the promising results. Combination of immunotherapies with chemotherapy in frontline treatment is being evaluated to increase the rate and depth of molecular remission. The use of tyrosine kinase inhibitors and immunotherapy in Ph-positive ALL has shown unprecedented rates of remission and long-term cure. The development of potentially curative treatment modalities for older ALL patients who cannot receive intensive chemotherapy is also highlighted.