|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 1 | Page : 139-140
Authors' reply to Jayakar and Bagal et al.
Hasmukh Jain, Kunal Jobanputra, Jayashree Thorat
Department of Medical Oncology, Tata Memorial Hospital; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
|Date of Submission||22-Jan-2020|
|Date of Acceptance||22-Jan-2020|
|Date of Web Publication||24-Feb-2020|
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jain H, Jobanputra K, Thorat J. Authors' reply to Jayakar and Bagal et al. Cancer Res Stat Treat 2020;3:139-40
We agree with Jayakar's comment that a chemotherapy-free regimen of blinatumomab and tyrosine kinase inhibitors appears to be promising as a bridge therapy or as an alternative to allogeneic stem-cell transplant in Ph + ALL. It would be exciting to see the results of the ongoing Phase II trial of the combination of ponatinib and blinatumomab in the above cohort.
Bagal and Munot have rightly pointed out the overlap between the side effects of ponatinib and nilotinib. However, the mechanisms behind the cardiovascular effects of these two drugs differ marginally. According to a study in mice, ponatinib predisposed to a prothrombotic state by altering the genetic expression of procoagulant and fibrinolytic proteins, while nilotinib increased the Factor VIIa activity with less effects on gene expression. In addition, nilotinib was found to increase ex vivo platelet adhesion and thrombin generation in humans; on the contrary, ponatinib showed opposite effects on ex vivo human platelet aggregation and activation.
The combination of ponatinib and asciminib has been shown to reduce tumor growth and modestly improve survival in mice injected with a T315I-inclusive mutant. The combination was well tolerated at the physiologically achievable doses, offering the prospect of using a nontoxic lower dose of ponatinib with asciminib.,
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jayakar V. Ponatinib: Harnessing the elixir potential. Cancer Res Stat Treat 2020;3:138-9. [Full text]
Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemia. Available from: https://clinicaltrials.gov/ct2/show/NCT03263572
. [Last accessed on 2020 Jan 20].
Bagal B, Munot P. Ponatinib in chronic myeloid leukemia: Finally getting it right? Cancer Res Stat Treat 2020;3:137-8. [Full text]
Pouwer MG, Pieterman EJ, Verschuren L, Caspers MP, Kluft C, Garcia RA, et al
. The BCR-ABL1 inhibitors imatinib and ponatinib decrease plasma cholesterol and atherosclerosis, and nilotinib and ponatinib activate coagulation in a translational mouse model. Front Cardiovasc Med 2018;5:55.
Eide CA, Zabriskie MS, Savage Stevens SL, Antelope O, Vellore NA, Than H, et al
. Combining the allosteric inhibitor asciminib with ponatinib suppresses emergence of and restores efficacy against highly resistant bCR-ABL1 mutants. Cancer Cell 2019;36:431-43.e5.
Jain H, Thorat J, Sengar M, Dubey A. Ponatinib: A drug review. Cancer Res Stat Treat 2019;2:190-6. [Full text]