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ASH 2001 Orlando, Florida, Part 3
Editor's Note: Peter Rowbotham attended the 2001 meeting of the American Society of Hematology, held from Dec. 7-11 in Orlando, Florida, U.S.A. Rowbotham, whose wife has CML, has long dedicated himself to researching new treatment advances and passing that information along to others. Here, his series is presented verbatim.
By Peter Rowbotham
[Note from Peter: This report, and any following reports, are based on written notes which may be inaccurate or incomplete. Patients should check with medical professionals as necessary.]
There seem to be a lot of papers and attention being given to AML (acute myelogeneous leukemia) at this ASH meeting. AML has some similarities with the acute (blastic) phase of CML, so it is good to keep an eye on what is happening, especially since blastic transformation in CML is still a largely intractable problem.
While Gleevec is not the usual therapy of choice in AML, I did note that a poster to be presented tomorrow reports a very favourable result in one AML patient taking Gleevec. Even more noteworthy is the develoment of the second targeted therapy that blocks the effects of a mutant gene in a type of leukemia (AML) which will be used in a trial setting. The trial will start soon at MSKC and Dana Farber. Some 30% of AML patients have a mutation called FLT3 (a type of growth factor). This new tyrosine kinase inhibitor, PKC412, is being developed by Novartis. The Leukemia and Lymphoma Society news release (Dec. 7/01) states that, "The new clinical trials are anticipated with the hope that they will result in the same success for AML patients that Gleevec has had for CML patients."
This is a very important and exciting development, which highlights the extraordinary importance of targeted therapies. VEGF (antiangiogenesis) inhibition is not strictly a targeted therapy, but it is often discussed in this context. There is a lot of interest in this whole area of antiangiogenesis therapy. One speaker today suggested that its greatest promise was not in treating solid tumours, but rather hematological malignancies. As many will know, Novartis has a VEGFR2 inhibitor in trials for patients with AML, MDS, and CML in the blastic phase. I previously reported that there was evidence that both VEGFR1 and VEGFR2 needed to be inhibited to get the best results, and that point was made again here. It may also be crucially important, in order to get the maximum therapeutic benefit, to combine angiogenesis inhibitors with other drugs.
This is certainly an increasingly highlighted research topic that is likely to be valuable for CML patients. Drugs used in CML treatment, such as IFN, Arsenic Trioxide, and even Gleevec (through PDGF inhibition) are all antiangiogenic in varying degrees, and this may be beneficial. Platelets and neutrophils are associated with VEGF, so I speculate (note!) that neutropenia may have some benefit from this perspective.
Druker repeated his view that neutropenia may have therapeutic value. He also said that higher Gleevec doses (e.g. 600mg) may be beneficial. The problem is that higher doses, by attacking the CML cells more aggressively, may lead to more neutropenia. Cycling off the drug has been one way to deal with this, but as a Novartis speaker said there is much debate about [the advisability of] this, and although there is little data, it "could be relevant to resistance."
My very inexpert judgment is that this cycling on and off is not a good thing if it can be avoided (although, paradoxically, there may sometimes be a good reason to cycle off for perhaps two months or so if resistance actually develops). The solution may be to add a growth factor such as G-CSF or GM-CSF. A study by OHSU indicates that there are no apparent adverse effects from doing this. It also says that this "may be beneficial with STI571 through immune modulatory and/or cell cycle effects; clinical trials are planned to explore these hypotheses." My notes say that the study suggests that it "seems to increase the number of major responses." That would be very good news; so good that I am concerned that I may have written it down wrong! So check with OHSU!!
Tomorrow will be a busy day, but if I get a spare moment in the evening, I will try and report further.
Cheers,
Source: Peter Rowbotham, reprinted with permission
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