New Biological Insights and Recent Therapeutic Advances in the Management of Acute and Chronic Leukemias and Myelodysplastic SyndromesClinical experience with omacetaxine mepesuccinate for patients with CML
4:33 minutes.
TRANSCRIPTION:
DR KANTARJIAN: Omacetaxine is the old homoharringtonine. We changed the name. This is probably the drug that had the longest track record to an FDA approval, because we started using it in 1988, initially for AML, and finally we got an approval in 2012. It is not in the same league as the TKIs in terms of the efficacy in chronic myeloid leukemia. And certainly the price does not help in its more common use in the practice. If it was a less expensive drug, I think I would certainly use it much more in patients who have failed TKIs or in combination with TKIs in accelerated disease. Also, it could have a role in the eradication of minimal residual disease, but that remains investigational. I think also omacetaxine could have a potential significant role in acute myeloid leukemia and perhaps myelodysplastic syndrome, so these are areas of investigation that we are interested in. DR LOVE: Can you talk a little bit more about what it is? And I know you’ve told me in the past that it has an interesting history, and how it works? DR KANTARJIAN: It’s a protein synthesis inhibitor. And in the setting of CML it’s supposed to inhibit the protein synthesis related to the BCR-ABL more effectively than in the normal cells, and, therefore, it can cause the cell death and death pattern. It is a natural product. It came out of the Mao Tse-Tung Red Book — was it the Red Book? The Red Book, right? DR SCHIFFER: It was The Little Red Book. DR KANTARJIAN: The medicine Red Book. So among the teachings of Mao Tse-Tung was that all cures of medicine will come through Chinese herbal medicine. And this is how ATRA was developed for acute promyelocytic leukemia. This is how arsenic trioxide was investigated, although it’s not an herb. There’s a red stone that they used to lick and find that the patients do better when they lick that stone, which is tetra-arsenic tetrasulfide. But homoharringtonine came out of those teachings with the early Chinese medical literature in the ‘80s, demonstrating its activity in acute myeloid leukemia, in chronic myeloid leukemia, so I think it’s a drug that could have potential expanded utilities, maybe in lymphoma. But nobody has studied it effectively in the United States, because when it came into the US it was used as short infusions, which caused severe hypotension in a third of the patients. So people abandoned it until continuous infusions and subcutaneous schedules avoided those toxicities and we got the approval in CML. DR LOVE: So how often do you use the drug, and in what clinical situations, Hagop? DR KANTARJIAN: I use it mostly in patients with transformation. And so I usually do not use TKIs as a single agent. I use them in combination. Usually the drugs I use them in combination with are decitabine, omacetaxine or AML-type therapies. DR LOVE: So Dave, what’s your experience with this agent? DR STEENSMA: Yes. It’s limited. I’ve used it only in 2 patients. One was a schizophrenic man who all of the TKIs had drug-drug interactions that were quite major with the agents that he needed in order to keep him out of an institution. And the other was a man who was a homeless man who had no insurance for oral agents but was able to at least come into the clinic for injectable — it seems silly, but these are exceptional circumstances. DR LOVE: How did these 2 people do? DR STEENSMA: So the schizophrenic man actually was doing okay, and then he fell asleep with a cigarette and his mattress went on fire and he died of smoke inhalation. DR LOVE: Wow! DR STEENSMA: And the homeless man was lost to follow-up. That being said, both of them were responding to the drug. DR LOVE: And how were they tolerating the agent? DR STEENSMA: The GI side effects are meaningful. Cytopenias are also problematic with the agent. But they were both manageable. DR LOVE: Doug, any experience? DR SMITH: Yes, I look at it as a low-dose chemotherapy or even a real-dose chemotherapy, a little bit different in approach. I use it for super high-risk patients or advancing, accelerated blast crisis patients when they’ve been through other TKIs that are not responding and they need some cytotoxicity along with a TKI, for example. |