More PreMF patients within ET cohorts than currently diagnosed

[Fishermangents]

It already has been said at other occasions: ET is not so 'innocent' as we may think. This article suggests that there are significantly more PreMF cases amongst ET diagnosed patients than we currently acknowledge. That means that imetelstat may very well play a life saving role for a significant subgroup of ET diagnosed patients, who actually are in the phase of developing MF.

Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria
Leukemia Advance Online Publication, Gisslinger et al, 12 February 2016

Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n=238) or the WHO guidelines (n=232). The BCSH-defined ET cohort was re-evaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management.

link: http://www.nature.com/leu/journal/vaop/ ... 5360a.html

[irishtrader52]

fisher - this is an important point. I think that it is generally agreed by MPN experts that imetelstat may not be indicated for all ET patients (risk:reward) but is likely life-saving in pre-MF ET. I have read some studies that suggest research is getting closer to the biomarkers that could better predict liklihood of ET transformation to MF.

[Fishermangents]

When imetelstat is approved for MF, patients diagnosed with preMF-ET will get access to imetelstat also. Even in cases that there may still be some doubts, doctors can easily advocate towards MF diagnosis, certainly if fibrosis is already noticable in the bonemarrow through biopsy, possibly accompanied with elevant LDH and enlarged spleen (both very frequent in ET patients). This further underlines the importance of Baerlocher's ET study outcomes.

[huntingonthebluffs]

Sorry for my repetitions on this but I think it would help everyone to occasionally return to the ImetelChat archives and review some of the old posts when they have some time to research.

This thread was from early 2016 (page 44 of posts). It among other things, points out the commercial potential of Imetelstat for a significant percentage of ET patients likely to transition to MF. Of course, this usage would be off label, but also points to the importance of first approval for the standalone use of Imetelstat in MDS and MF. It easy to get caught up in the importance of combinations, however first things first and I think Geron is rightly focused on the doing the next right thing first.

Given the nature of competition working against Geron in ways we can’t always see, and realizing Geron’s public plans are not written in indelible ink, changes to plans are not always a reflection of ineffective execution and probably most often responses to outside influences.

Secondly, I hope I’m wrong, but I do have a healthy fear of Geron getting to far in front of things with the combination trials and delivery options. I think it likely brings the sinister elements to more aggressively focus on how Imetelstat’s success and progress could/will impact financials of BP. So for me, what I think I see going on now I think we are all better off if Geron shifts gears down a bit. Once we have commercial use of Imetelstat for MDS and MF, increased presence and financial resources can better flow into the next steps at that point. I’m not sure regulators and insurance companies will support off label use to flourish but I hope it will for those patients with unmet needs. Finding a way to use Imetelstat off label where appropriate is critical and only not in the best interests of BP.

[Hoosier Investor]

Hat tip to Irishtrader52 and her late husband. She's a legitimate badass, and her late husband was a courageous hero deserving of the highest respect. They were both among my earliest thoughts when Imetelstat's positive TLR were announced in January.

Irish,
Please know that we appreciate all of your (and husband's) collective efforts and both of you are still in our thoughts. We hope you're doing well, and we'd welcome you back with open arms if you have time & desire to re-engage as we approach the MF topline results.

[biopearl123]

Seconded wholeheartedly!! It was so troubling to me when Irish’s husband had to stop treatment because they could not afford constant travel from the Southeast to Rochester. Time to make this drug available to those who need it.

[jingledsassy]

Travel to Rochester from Toledo takes 91/2 hrs.....the Kahler hotel's elevator goes down to a mini mall and cafeteria witch also connects to the main elevators of the Mayo Clinic....All surgeries are done at St Mary's hospital about 6 blocks from the clinic......Top of the line if you have a serious medical problem....to express it [without referrals] simply go to St Mary's emergency unit and you are in their system the same day....sort the insurance issues out later.....Ps they also have suites with your own Chef......2010 rates were $700 a night......

[kmall]

Hunt- Thanks for bringing this boards past forward. For a newbie to Imetechat like myself, 1st post 2019, both Irishtrader52 and Fishermagnets are the stuff of legend. And yes Hoosier, caregivers for patients with these Hematological Disorders can generally be categorized in the badass column.....they have to be! -Kmall