|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 1 | Page : 138-139
Ponatinib: Harnessing the elixir potential
Department of Haemato-Oncology, Kingston Hospital NHS Foundation Trust; Lead for Commercial Education and Training, Haematology Institute, King's College Health Partners; King's College, London, UK
|Date of Submission||13-Jan-2020|
|Date of Acceptance||13-Jan-2020|
|Date of Web Publication||24-Feb-2020|
Kingston Hospital, Kingston upon the Thames, London
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jayakar V. Ponatinib: Harnessing the elixir potential. Cancer Res Stat Treat 2020;3:138-9
In this painstakingly thorough and meticulous drug review, the authors provide an up-to-date evidence-based monograph on ponatinib.
The mechanism of its action could have been explained better and figuratively. The T315I mutation deposits a bulky isoleucine amino acid residue in the BCR-ABL oncogene pocket near-completely blocking it, making it challenging and impossible for the first- and second-generation tyrosine kinase inhibitors (TKIs) to navigate through this tight pocket. Ponatinib, with its gracile neck-like structure, is the only TKI that can circumnavigate this gridlock displacing the isoleucine residue;, therefore, breaking the T315I impasse.
Although the authors describe the phase II trial involving the combination of ponatinib with hyper CVAD in Philadelphia-positive (Ph pos) acute lymphoblastic leukemia (ALL) in detail, I want to register the growing enthusiasm and promise surrounding chemotherapy-free regimens in combination with ponatinib in the treatment of de novo Ph pos ALL– TKI. The D-ALBA study utilizing dasatinib with blinatumomab in Ph pos ALL with promising results was presented as a late-breaking abstract at the ASH 2019 congress. The results of ponatinib with blinatumomab in a similar disease cohort are eagerly awaited.
Learning to personalize the ponatinib doses (15–45 mg/day) to the patient narratives with pragmatic reductions and de-escalation commensurate to their cardiovascular/atherosclerotic risk status, rather than a “one size fits all”-blanket approach, seems to be the sensible way forward to mitigate toxicity.
The future truly lies in its judicious dosing and combination with chemo-free constructs in this historically “difficult to treat” cohort of Ph pos ALL.
Ponatinib's most exciting indication is likely to find its niche in these chemo-free combinations (immune checkpoint inhibitors and chimeric antigen receptor T-cells) rather than its single-agent use.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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