(032) Clinical Impact of Proton-Pump Inhibitor Therapy in Combination with Certain Tyrosine Kinase Inhibitors in Adult Patients with Chronic Myeloid Leukemia

Poster Abstract:

Background: Bosutinib, dasatinib, and nilotinib are all listed as Category 1 Recommendations in the National Comprehensive Cancer Network (NCCN) Guidelines as both first-line and subsequent therapy options for CML. Providers often prescribe these tyrosine kinase inhibitors (TKI's) concomitantly with proton pump inhibitors (PPI’s). Pharmacokinetic studies have demonstrated that concomitant administration of certain TKI's, such as those mentioned about, with a PPI results in lower TKI plasma concentrations which is likely due to an interaction resulting in impaired TKI absorption. While pharmacokinetic data has demonstrated a reduction in TKI plasma concentrations, real-world application of this in terms of clinical outcomes has been inadequately studied.

Objective: The objective of this study is to assess the impact of PPI therapy on clinical response to the TKI’s bosutinib, dasatinib, and nilotinib for up to one year in adult patients with CML.

Methods: This study is a retrospective chart review and included 47 total patients. Patients were separated into two groups: those treated with the TKI's mentioned above only (TKI cohort) and those receiving a TKI concomitantly with a PPI (TKI-PPI cohort). Data was evaluated to assess early treatment response to TKI therapy as assessed by BCR::ABL1 levels at 3, 6, and 12 months in the TKI and TKI-PPI cohorts. Secondary endpoints include the rate of discontinuation of TKI therapy, time to TKI discontinuation, progression to accelerated or blast phase CML, mortality, dose reductions due to adverse events/tolerability, and discontinuation due to adverse events/tolerability.
Discussion/

Conclusion: This study resulted in no statistical difference after evaluating all endpoints. Several limitations were present such as the reliance on patient-reported PPI use, missing data in the electronic medical record, and an overall small sample size. The interaction between PPI’s and the TKI’s bosutinib, dasatinib, and nilotinib may not impact efficacy when treating patients with CML, but additional studies are needed to confirm.

References (must also be included in final poster): 1. Takahashi N, Miura M, Niioka T, Sawada K. Influence of H2-receptor antagonists and proton pump inhibitors on dasatinib pharmacokinetics in Japanese leukemia patients. Cancer Chemother Pharmacol. 2012;69(4):999-1004. doi:10.1007/s00280-011- 1797-3
2. La Cava P, Chiarenza A, Tibullo D, et al. The Effect of the Interaction between Proton Pump Inhibitors (PPI) and Tyrosine Kinase Inhibitors (Imatinib, Nilotinib and Dasatinib). Blood. 2007;110(11):2957. doi.org/10.1182/blood.V110.11.2957.2957
3. Koutake, Y., Taniguchi, J., Yasumori, N. et al. Influence of proton pump inhibitors and H2-receptor antagonists on the efficacy and safety of dasatinib in chronic myeloid leukemia patients. Int J Hematol. 2020;111(6):826-832. doi:https://doi.org/10.1007/s12185-020-02845-6
4. Yin O, Giles F, Baccarani M, et al. Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia. Cancer Chemother Pharmacol. 2012;70(2):345-350. doi:https://doi.org/10.1007/s00280-012-1881-3