Relapsed Philadelphia chromosome (Ph) positive Acute Lymphoblastic Leukemia (ALL) is an aggressive lymphoid malignancy with a poor prognosis and no randomized studies demonstrating superiority of any single salvage regimen. We present the case of a 33-year-old woman with relapsed Ph positive precursor (pre) B-cell ALL with rapidly rising peripheral blasts while on blinatumomab monotherapy initially, but ultimately responded with the addition of Vincristine Sulfate Liposome Injection (VSLI). Ponatinib was added later when it became available for the patient, and she ultimately achieved a complete remission. Further study is warranted to explore mechanisms of potential synergy, and the safety and efficacy of the combination of blinatumomab and VSLI.