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Experience with Omacetaxine for TKI-Resistant TKI CML

Insights From: Javier Pinilla-Ibarz, MD, PhD, Moffitt Cancer Center; Camille N. Abboud, MD, Washington University School of Medicine
Published: Wednesday, Jan 25, 2017


Transcript:

Javier Pinilla-Ibarz, MD, PhD:
Omacetaxine has been tested, and been approved for the treatment of chronic myeloid leukemia after intolerance or resistance to more than 2 tyrosine kinase inhibitors. In this setting, there are several trials that were published, and have been done a few years ago, where this drug showed efficacy in the control of the disease, either in the resistance or intolerance setting of chronic myeloid leukemia.

I’ve been using omacetaxine for patients with chronic phase CML, or even an accelerated phase CML, who already have failed several lines of tyrosine kinase inhibitors. In this setting, of course, it’s one alternative that completely changes the mechanism of action with which we treat our patients. In this scenario, there are data to support the use of this drug because of the effectiveness of controlling the symptoms of the disease.

Omacetaxine has been tested many years ago in several clinical trials. There is no doubt that there is efficacy in chronic phase or accelerated phase chronic myeloid leukemia. The rates of response are not as high as for the tyrosine kinase inhibitor in the frontline, the second, or even third line. However, when all the tyrosine kinase inhibitors are not a way to treat those patients, omacetaxine has around a 15% of response in these patients in terms of eradication of the Philadelphia chromosome.

Camille N. Abboud, MD: Omacetaxine has a role in patients who are resistant to multiple TKIs, especially later when they are developing accelerated phase. As it does not rely on its mechanism on the presence or absence of certain tyrosine kinase or BCR-ABL mutation, in that regard, this drug is very effective in rapidly lowering the count and promoting a hematologic response in patients who, otherwise, are totally resistant to TKI therapy or could not tolerate them. The main side effects that one has to monitor in these instances are GI toxicity, diarrhea, and certainly pancytopenia or lowering of the blood counts.

In my own practice, I have used omacetaxine in patients in chronic phase when they could not tolerate TKIs, and I have used it in patients with accelerated or blast phase when I needed to obtain rapid hematologic response, usually as a bridge to transplant, if the patient has a donor waiting or needs time to identify a donor for transplant.

In terms of being able to lower the counts, omacetaxine is a very effective drug, especially in patients who have been resistant to achieving hematologic responses with all the previous TKIs mentioned. I have not used omacetaxine with ponatinib, which is usually approved for patients who are resistant to all other TKIs, because of the side effects of both drugs together. That said, omacetaxine is able to lower the white blood cell count in patients with chronic or accelerated phase CML. Therefore, it’s a drug that should be examined further in that setting.

Transcript Edited for Clarity
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Transcript:

Javier Pinilla-Ibarz, MD, PhD:
Omacetaxine has been tested, and been approved for the treatment of chronic myeloid leukemia after intolerance or resistance to more than 2 tyrosine kinase inhibitors. In this setting, there are several trials that were published, and have been done a few years ago, where this drug showed efficacy in the control of the disease, either in the resistance or intolerance setting of chronic myeloid leukemia.

I’ve been using omacetaxine for patients with chronic phase CML, or even an accelerated phase CML, who already have failed several lines of tyrosine kinase inhibitors. In this setting, of course, it’s one alternative that completely changes the mechanism of action with which we treat our patients. In this scenario, there are data to support the use of this drug because of the effectiveness of controlling the symptoms of the disease.

Omacetaxine has been tested many years ago in several clinical trials. There is no doubt that there is efficacy in chronic phase or accelerated phase chronic myeloid leukemia. The rates of response are not as high as for the tyrosine kinase inhibitor in the frontline, the second, or even third line. However, when all the tyrosine kinase inhibitors are not a way to treat those patients, omacetaxine has around a 15% of response in these patients in terms of eradication of the Philadelphia chromosome.

Camille N. Abboud, MD: Omacetaxine has a role in patients who are resistant to multiple TKIs, especially later when they are developing accelerated phase. As it does not rely on its mechanism on the presence or absence of certain tyrosine kinase or BCR-ABL mutation, in that regard, this drug is very effective in rapidly lowering the count and promoting a hematologic response in patients who, otherwise, are totally resistant to TKI therapy or could not tolerate them. The main side effects that one has to monitor in these instances are GI toxicity, diarrhea, and certainly pancytopenia or lowering of the blood counts.

In my own practice, I have used omacetaxine in patients in chronic phase when they could not tolerate TKIs, and I have used it in patients with accelerated or blast phase when I needed to obtain rapid hematologic response, usually as a bridge to transplant, if the patient has a donor waiting or needs time to identify a donor for transplant.

In terms of being able to lower the counts, omacetaxine is a very effective drug, especially in patients who have been resistant to achieving hematologic responses with all the previous TKIs mentioned. I have not used omacetaxine with ponatinib, which is usually approved for patients who are resistant to all other TKIs, because of the side effects of both drugs together. That said, omacetaxine is able to lower the white blood cell count in patients with chronic or accelerated phase CML. Therefore, it’s a drug that should be examined further in that setting.

Transcript Edited for Clarity
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