European Medical Journal (Aug 2017)
Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia
Abstract
Acute lymphoblastic leukaemia (ALL) in adults has a survival rate of 40–50% at 5 years, with a high relapse rate after first-line chemotherapy. After relapse, results with salvage therapy are currently unsatisfactory. Therefore, both the optimisation of front-line therapy to reduce relapse incidence and the search for effective salvage therapies for relapsed/refractory (r/r) ALL have been of great interest to the medical community in recent years. The well-characterised expression of well-defined cell-surface antigens in B cell ALL (B)-ALL and T cell (T)-ALL, such as CD19, CD20, CD22, and CD52, has led to the development of several immunotherapy strategies, comprising ‘nude’ monoclonal antibodies (moAbs), conjugated moAbs, bispeciphic, or highly sophisticated chimeric antigen receptor (CAR)-T cell therapy. Recently, both the bispecific moAb blinatumomab (anti-CD19 coupled with a CD3 recognition subunit) and the conjugated anti-CD22 moAb inotuzumab-ozogamicin have resulted in higher remission rates (44% versus 25%, and 80.7% versus 29.4%, respectively) and survival advantages (median overall survival [OS]: 7.7 months versus 4 months, and 7.7 months versus 6.7 months, respectively) in patients with r/r B-ALL when compared to standard salvage chemotherapy-based regimens. On the other hand, preliminary reports show feasibility and unprecedented response rates of ≤90% in highly refractory children and adults treated with CAR-modified T cells targeting the B cell specific CD19 antigen, which seem to be durable in a significant proportion of patients. Furthermore, the addition of anti-CD20 moAb rituximab to front-line standard chemotherapy in patients with CD20+ B-ALL has resulted in a clinical benefit, with prolongation of response duration and survival (3-year leukaemia-free survival and OS: 70% versus 38%; p<0.001, and 75% versus 47%; p=0.003). In conclusion, immunotherapy is currently providing additional options for high-risk ALL patients both in front-line or advanced phase. Nonetheless, the optimal positioning of these novel agents, specially in relation to allogeneic haematopoietic stem-cell transplantion, needs to be clarified. This article aims to review several of these new therapeutic immunotherapy options available for patients with adult ALL, as well as their specific toxicity profile.
