Planning Your Next Move in Philadelphia Chromosome Positive Leukaemias

Abstract

The meeting was arranged as a series of conversations between experts, following a question and answer format with two speakers in each presentation. In the first presentation, Dr Soverini and Prof Lion discussed the importance of the timing and depth of response with respect to clinical outcomes in Philadelphia chromosome positive (Ph+) leukaemias. They showed how sensitive and reproducible measurements of molecular response (MR) and the proper interpretation of laboratory data are critical to correctly inform therapeutic decisions in patients with chronic myeloid leukaemia (CML) and Ph+ acute lymphoblastic leukaemias (ALL). Detection of BCR-ABL mutations can establish the need for treatment change and, in some cases, indicate which tyrosine-kinase inhibitor (TKI) is most likely to be effective. The speakers addressed the need for more sensitive and accurate methods to monitor minimal residual disease (MRD) and detect mutations that drive resistance to TKI therapy. They explored two distinct patterns of mutation observed in patients with >1 mutation (polyclonal and compound mutations) and how in addition to selecting the most appropriate TKI it is also important to consider the most appropriate dose. In the second presentation, Dr Bassan and Prof Dr Junghanß discussed the evolving treatment landscape for Ph+ ALL, including the role of TKI, chemotherapy, and allogenic stem cell transplantation (SCT). The advent of TKI has improved the prognosis for Ph+ ALL, allowing many more patients to achieve complete remission and be considered for allogeneic SCT. However, treatment-related mortality remains a significant issue after allogenic SCT affecting 20–33% of patients. Studies show that early death rates are lower for patients receiving ‘light’ chemotherapy and TKI with steroids in place of chemotherapy. Furthermore, for patients achieving complete MR, in some studies there is no difference in outcome between those who undergo allogenic SCT and those who do not, provided that the latter subgroup was selected according to absence of residual disease by PCR analysis. Such data suggest that, in Ph+ ALL, novel therapeutic approaches may in some patients obviate the need for intensive chemotherapy and allogeneic SCT. Studies are now ongoing to explore whether Ph+ ALL patients can abstain from allogenic SCT through selection of the strongest TKI upfront and whether chemotherapy-free regimens might be an option.