Durable Molecular Remission in an Elderly Patient Affected by Relapsed Ph'+ Acute Lymphoblastic Leukemia with T315I and Concomitant p190 and p210 Expression Achieved by Inotuzumab and Ponatinib

An unmet clinical need currently exists for elderly patients with relapsed/resistant (R/R) Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL), nearly all who have a very poor prognosis. This includes patients already exposed to the first or second generation tyrosine kinase inhibitors (TKIs) and therefore has few treatment options available. New immunotherapies and targeted agents have shown encouraging activity in R/R ALL irrespective of age. Inotuzumab (InO), a humanized anti-CD22 monoclonal antibody, has potentially beneficial clinical effects in patients with resistant and difficult-to-treat disease in whom prior TKIs have failed. However, InO, as a single agent, did not show durable response and longer progression free survival and overall survival in R/R Ph positive ALL patients compared with those treated with standard chemotherapy. We observed a durable molecular remission (7 months) in an elderly patient affected by Ph'+ ALL with T315I and concomitant p190 and p210 expression achieved by concomitant therapy of InO (for 4 cycles) and ponatinib (15 mg/daily) followed by ponatinib (15 mg/daily) only as maintenance therapy. These findings suggest that elderly R/R Ph positive patients who cannot proceed to the transplant might benefit by concomitant immunotherapy and TKIs aimed to deepen the responses and prolong CR and outcomes.