How should we treat a patient with relapsed Ph-negative B-ALL and what novel approaches are being investigated?

Despite significant improvements in outcome of newly diagnosed B-precursor ALL, the results in relapsed or refractory adult ALL are overall poor. Large retrospective studies revealed significant differences in terms of outcome, with particularly poor response rates in early or refractory relapses, whereas late relapses usually respond very well to repeated standard induction. Particularly new immunotherapy compounds like the CD19 bispecific antibody Blinatumomab and the conjugated CD22 antibody Inotuzumab yielded promising response rates compared to standard therapies in randomised trials. Long-term survival is however still poor. The optimal use of these compounds remains to be defined. Chimeric antigen receptor T-cells are another promising treatment approach and multicenter clinical trials in adult ALL are awaited. For selected patients molecular directed therapies may have a role in relapsed ALL; standard diagnostic algorithms need to be defined. One of the major challenges is to define the role of stem cell transplantation after relapse. Whereas this procedure appears to be the only chance for cure, the mortality and relapse rate are still high and optimisation is urgently needed. Future strategies include optimised use of new compounds as part of combination regimens and the earlier treatment of upcoming relapse in the situation of persistent or recurrent minimal residual disease.