2017 Review Article in American Journal of Hematology

[biopearl]

Happy New Year greetings to all. The New Year brings us an excellent new article from Dr. T (available on internet):

Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management (published in Nov 2016)

Imetelstat mentioned in last paragraph. Dr. T reviews Comfort studies. Same lukewarm conclusions. Recommends skipping JAK inhibitors for some patients and going right to "experimental agents" to reduce risk of transformation to AML. Worth reading and maybe Fish can post the reference.

[scottmayhew]

" Same lukewarm conclusions"

by Dr. T? About Imetelstat? or same lukewarm conclusions from the article's author? Has Dr. T. gone from "tantamount to a cure" to being lukewarm on the efficacy of Imetelstat? I know in previous communications (was it in SF last year) he was unexcited by all treatment approaches, which some took to include Imetelstat...is this more of the same? Can you expound a little.

[scottmayhew]

http://onlinelibrary.wiley.com/doi/10.1 ... 24592/full

"Currently, many other drugs are being tested for their therapeutic value in MF and the most intriguing results were recently reported with the use of imetelestat, which is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase reverse transcriptase. In the particular study, imetelstat was administered as a 2-hour intravenous infusion (9.4 mg per kilogram of body weight) every 1 to 3 weeks. A complete or partial remission occurred in 7 of 33 patients (21%), with a median duration of response of 18 months for complete responses. Bone marrow fibrosis was reversed in all 4 patients who had a complete response, and a molecular response occurred in three of the four patients. Response rates were 32% among patients without an ASXL1 mutation versus 0% among those with an ASXL1 mutation. The rate of complete response was 38% among patients with a mutation in SF3B1 or U2AF1 versus 4% among patients without a mutation in these genes. Treatment-related adverse events included grade 4 thrombocytopenia (in 18% of patients), grade 4 neutropenia (in 12%), grade 3 anemia (in 30%), and grade 1 or 2 elevation in levels of total bilirubin (in 12%), alkaline phosphatase (in 21%), and aspartate aminotransferase (in 27%); these observations have led to additional clinical trials in other myeloid malignancies [61, 80, 81]."

...is this the same article? reference states its from the NEJM from 2015...which would point to the Mayo study. Is this really new?

[biopearl]

Now hold on here laddie my reference to leukwarm conclusions referenced the Comfort study, not Imetelstat. I continue to be struck about Dr Ts strong hints that Imetelstat may prevent progression to AML sorry for the confusion bp

[Fishermangents]

Happy New Year to you all!

Bio/Scott: thanks for posting this interesting article. I will upload it to imetelstat.info

[biopearl]

"In my opinion, all non-transplant candidates with high or intermediate-2 risk disease should first be offered participation ininvestigational drug therapy before treatment with conventional drugs including JAK inhibitors. This is because the latter agents are unlikely to significantly modify the natural history of the disease and would not prevent progression into acute leukemia." Its pretty clear, and I think we have discussed this before that Dr. T is saying that Imetelstat in this group FIRST. He also has implied that prior treatment with JAK inhibitors my alter the later response to Imetelstat and not in a good way. I hope that is not a problem with the very selected J an J group that have all receive prior treatment and failed as this could delay development. I find Dr.T's statements strong and encouraging. Please add your thoughts...bp

[scottmayhew]

Right! You did say Comfort...my bad.

[scottmayhew]

Anyone know if in the Mayo Study had anyone who had clinically responded to Imetelstat previously failed on Jakafi and if so, whether their response to Imetelstat had been delayed in relation to other responses? Clearly, Tefferi has an opinion but is it based on conjecture or observation?

[biopearl]

Hi Scotty, yes there were as far as I remember. Ligas, has parsed out the numbers and might provide them for us. bp