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"I sleep less and work more. These are exciting times." |
CMLSupport: So much emphasis is being placed on the ability of STI571 to induce hematologic remission (at least by the public). Shouldn't the focus be on cytogenetics instead?
Druker: All of our patients have failed Interferon, many with poorly controlled blood counts and severe side effects from Interferon. To have normal blood counts and feel well on STI571 is important in its own right.
Major cytogenetic responses correlate with increased survival for Interferon-treated patients. However, it is too early to know if this will be true for STI571. Nevertheless, it is believed that improved survival is likely for patients with cytogenetic responses to STI571, but this will require longer followup than we currently have.
In the meantime, I am pleased that patients are leading high-quality lives with normal blood counts, regardless of cytogenetic responses.
CMLSupport: Does age and/or present health seem to be a factor in STI effectiveness when someone begins that treatment, and if so, in what way?
Druker: The major factor seems to be stage of disease: chronic versus accelerated versus blast.
Virtually all patients with chronic phase respond to STI571, whereas the number in blast phase is 70 percent. Responses in chronic phase have been durable, while only 20-30 percent of blast patients are having durable responses. (Please note, the response to chemotherapy in blast phase is 20 percent with durable responses less than 10 percent.) The data for accelerated phase are predictably intermediate.
CMLSupport: Can you offer any details about the results from the STI trials, such as cytogenetic remission rates? If not, when will that data be available to the public?
Druker: I am working on the update from the Phase I study right now. There will be a significant amount of information available in December presented at the American Society of Hematology meeting.
CMLSupport: What surprises, if any, have you encountered during the STI trials?
Druker: I have been most surprised by the minimal side effects of STI571.
There was no way to predict the side effect profile. I figured STI571 was either going to work well or not at all, so I am not overly surprised by how well it is working. I am, of course pleased.
I was actually a bit disappointed early on when we were seeing complete hematologic responses without cytogenetic response and had several possible explanations for this result. Fortunately, this did not last long, as we just needed to wait a bit longer to see the cytogenetic responses.
CMLSupport: What concerns do you have about STI at this point, and long term?
Druker: The durability of the responses, the emergence of resistance, and the possibility of long term side effects.
CMLSupport: If STI (or another medication) doesn't induce a complete cytogenetic remission, can a reduction in the Ph+ chromosome percentage at least lead to prolonged life, and what percentage should we "aim" for?
Druker: See above. The percentage used for major cytogenetic response is less than 35 percent Ph+.
CMLSupport: Do you think STI will become the new "standard" cure, replacing the BMT, or will it likely have to be used in conjunction with other treatments, such as Interferon and/or ARA-C?
Druker: Until it can be shown that STI can prolong survival or "cure" a fraction of CML patients, BMT will not be replaced.
Predictions for STI are quite variable in the absence of large amounts of data or long-term followup. I am working on the assumption that STI571 will be sufficient for some patients, others will require STI in combination with Interferon or Ara-C, and others will require BMT.
The task for the future is to identify which patients are which. That is, to individualize therapy so that patients can be cured with the minimally invasive therapy. This will be the major project in my laboratory for the next 5 or more years.
CMLSupport: What's the theory behind STI?
Druker: My view of chronic phase of CML is that the product of the Ph chromosome, Bcr-Abl, causes CML. STI571, by inactivating this abnormality, might be able to cure CML in its earliest stage. The problem is that as the disease progresses, additional mutations develop such that STI571 is no longer sufficient on its own. This is the problem in the blast phase.
The other issue is that there may only be a small percentage of patients with Bcr-Abl as the sole abnormality. That is why I am investigating combinations of STI571 with other anti-leukemic agents.
CMLSupport: What other, if any, new treatments show promise?
Druker: I am looking forward to the introduction of the once-per-week interferons. Can't say there are any other big breakthroughs, although many new agents are being tested.
CMLSupport: How do you keep up your hectic pace of worldwide travel to make STI presentations?
Druker: I sleep less and work more. These are exciting times.
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