(215) Safety of Combination Blinatumomab and Ponatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia in Blast Phase

Poster Abstract:

Background:
In patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) in blast phase, the combination of intensive chemotherapy with a BCR-ABL1 tyrosine kinase inhibitor (TKI) followed by allogeneic hematopoietic stem cell transplant (HSCT) has historically been standard of care (1). Limitations of first- and second-generation TKI combinations include relatively low complete molecular response (CMR) rates and emergence of mutations leading to TKI therapy resistance (2-4). Higher rates of CMR and improved overall survival have been reported with ponatinib, a potent third-generation pan-BCR-ABL1 TKI with activity in patients with Ph+ ALL resistant or intolerant to second-generation TKIs (5). Blinatumomab, a CD3-CD19 bispecific antibody, was initially approved in patients with relapsed or refractory Ph+ ALL (6). Recently, blinatumomab has been shown to be effective in the frontline setting (7). A recent phase II study investigated the combination of blinatumomab and ponatinib in the treatment of newly diagnosed Ph+ ALL, relapsed or refractory Ph+ ALL, and CML in blast phase (8). Among newly diagnosed Ph+ ALL patients, 87% of patients had a CMR, while CMR rates in relapsed or refractory Ph+ ALL and CML in blast phase were 79% and 33%, respectively (8). The results of this chemotherapy-free regimen prompted the current study to further characterize the safety of the blinatumomab-ponatinib regimen in Ph+ ALL and CML blast phase patients at a single institution with pragmatic inclusion and exclusion criteria, dose variability, and tolerability data.

Objectives:
The objective of this study is to evaluate safety and tolerability of blinatumomab-ponatinib in patients with Ph+ ALL and CML in blast phase.

Methods:
This single-centered, retrospective study includes adult patients with newly diagnosed Ph+ ALL, relapsed or refractory Ph+ ALL, or CML in blast phase who received blinatumomab and ponatinib combination therapy at Moffitt Cancer Center from January 1, 2017 to December 1, 2023. Safety data collected on each patient included incidence of grade 3-4 cytokine release syndrome, grade 3-4 neurological toxicities according to the NCI Common Toxicity Criteria for Adverse Event Reporting Version 5.0, and any additional clinically relevant adverse effect of any grade throughout treatment. For each treatment cycle, therapy interruptions, discontinuations, and dose modifications were documented for each patient. Data was collected from Moffitt Cancer Center’s electronic medical record and descriptive analyses used to evaluate safety outcomes. Results will be validated against previously published studies evaluating the combination regimen of blinatumomab and ponatinib.

Results and Conclusion Pending

References (must also be included in final poster): 1. National Comprehensive Cancer Network. Acute Lymphoblastic Leukemia (Version 2.2023). https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed December 21,2023.
2. Short NJ, Jabbour E, Sasaki K, et al. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2016;128(4):504-507. doi:10.1182/blood-2016-03-707562
3. Daver N, Thomas D, Ravandi F, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100(5):653-661. doi:10.3324/haematol.2014.118588
4. Ravandi F, O'Brien SM, Cortes JE, et al. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158-4164. doi:10.1002/cncr.29646
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8. Jabbour E, Short NJ, Jain N, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023;10(1):e24-e34. doi:10.1016/S2352-3026(22)00319-2
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