Recent Developments in Immunotherapy for Acute Lymphoblastic Leukemia

Despite high rates of initial response to frontline therapy, the prognosis of adult patients with acute lymphoblastic leukemia (ALL) is still unsatisfactory, as many of them fail to reach a stable complete molecular response and they ultimately relapse. Intensification of chemotherapy regimens has determined a survival improvement especially in younger patients, but this strategy is less effective in case of unfavourable, high-risk cytogenetics and it is not feasible in unfit patients. The number of target therapies for ALL patients has rapidly increased in the recent years. In particular, the use of drugs targeting either CD19 (blinatumomab and Chimeric Antigen Receptor-T cells) or CD22 (inotuzumab ozogamicin) led to unexpected high rates of deep/complete molecular response also in patients with relapsed/refractory disease after several lines of treatment, including allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, this huge degree of response has determined so far only a small improvement of survival due to the short duration of remission, in particular when early consolidation with HSCT could not be performed. Early employment of immunotherapy, either at diagnosis or at first remission, seems a promising strategy to be tested in future prospective trials.