Chemotherapy-free and reduced intensity approaches in elderly patients with B-lineage acute lymphoblastic leukemia

Management of older patients - defined by convention above the age of 60 years, but varying widely within study groups - with acute lymphoblastic leukemia (ALL) is still a challenge. The complete remission (CR) rate in these patients is lower than in other age groups and the percentage of deaths in induction or in CR remains high, ranging from 7 to 40%. Overall survival rates do not exceed 30%, depending on the age group included in the different trials group and on the follow-up duration. These unsatisfactory results are sustained by the fact that pre-existing comorbidities often hamper treatment delivery and if treatment intensification improves the CR rates it also increases toxicity and the percentage of deaths. Overall, the median life expectancy is rising world-wide, being in the western world around/over 80 years (and increasing); in addition, the proportion of elderly individuals is growing progressively. This means that the management of these frail patients represents a true clinical unmet need. While in Ph+ ALL the introduction of tyrosine kinase inhibitors (TKI) has markedly impacted on the outcome of patients of all ages, in Ph− ALL prognosis in the elderly still remains largely unsatisfactory. Novel strategies - mostly based on the use of monoclonal antibodies or of targeted strategies if druggable mutations can be identified - are largely needed. In the present review, we will discuss the past and current scenario, and provide an overview on the developing approaches for both Ph− and Ph+ elderly ALL, represented in particular by immunotherapy.