ALL-180 A Case of Refractory Philadelphia-Like Acute Lymphoblastic Leukemia Treated With Ruxolitinib/Blinatumomab and Ruxolitinib/Inotuzumab Ozogamicin Prior to Allogeneic Marrow Transplant.

CONTEXT: Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subset associated with genomic alterations. These alterations can be grouped into major subclasses that either phenocopy BCR-ABL1 or activate JAK/STAT signaling. Ongoing trials suggest that patients harboring ABL-class fusions are candidates for ABL1 inhibitors, whereas alterations activating the JAK-STAT pathway may be amenable to treatment with JAK inhibitors.

OBJECTIVE: We hereby describe the first case of the use of ruxolitinib in combination with blinatumomab and inotuzumab in relapsed Ph-like ALL.

DESIGN: Case report.

SETTING: Tertiary referral hospital.

PATIENTS OR OTHER PARTICIPANTS: Ph-like ALL patient harboring a CRLF2 mutation.

INTERVENTIONS: Our patient received three cycles of first-line Hyper-CVAD: 1A/1B and 2A. BMBx after the third cycle revealed persistent disease. He then received two cycles of second-line ruxolitinib/blinatumomab prior to disease progression. He was then treated with three cycles of third-line ruxolitinib/inotuzumab followed by allogeneic transplant. Reports encouraging the use of JAK inhibitors in CRLF2 Ph-like ALL exist for children, and trials are currently ongoing for adolescents and young adults [NCT03571321]. Ruxolitinib was used at a starting dose of 15 mg BID, as determined by initial dose escalation phase trials testing the safety of ruxolitinib in myelofibrosis. Dose titration (maximum 25 mg BID/100 mg QD) was implemented according to response and platelet and neutrophil counts.

MAIN OUTCOME MEASURES: Complete response (CR) and measurable residual disease (MRD).

RESULTS: After progressing on Hyper-CVAD, our patient switched to ruxolitinib/blinatumomab and achieved CR with negative MRD after only one cycle of treatment. He progressed on this regimen after cycle 2 and moved to third-line ruxolitinib/inotuzumab. After three cycles, he achieved CR and negative MRD and underwent allogeneic transplant from a matched unrelated donor. Today, our patient is 10 months post transplant and remains in clinical and molecular remission.

CONCLUSIONS: The combination of ruxolitinib plus blinatumomab or inotuzumab is a promising chemotherapy-free salvage regimen given outpatient for relapsed Ph-like ALL. It achieved CR in our patient prior to allo SCT with a limited side effect profile. Further clinical trials adding ruxolitinib to front-line and next-line therapies are needed.