New Treatment Strategies for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

To review recent studies that address important questions regarding the treatment of Philadelphia chromosome-positive ALL.

Less intensive non-myelosuppressive induction approaches can produce comparable anti-leukemic responses with less toxicity. Second-generation tyrosine kinase inhibitors (TKIs) are not clearly associated with superior outcomes compared to imatinib. Ponatinib is associated with lower early relapse rates, but has additional vascular risks. Patients achieving complete molecular response (CMR) appear to have comparable survivals with chemotherapy + TKI alone as compared with allogeneic stem cell transplant (alloSCT). In contrast, those not achieving CMR have superior outcomes with alloSCT. There is no clear evidence of benefit for post-transplant TKI therapy. Patients resistant to chemotherapy + TKIs may respond to blinatumomab or inotuzumab; these agents may also convert some patients to CMR. Future studies should further explore the potential of ponatinib and antibody-based therapies to more precisely define optimal molecular responses.