For all interested I researched the subject matter of April 12th Meeting which should be fascinating.
4th annual Florence-Miami Patient Conference on Myeloproliferative Neoplasms
Lois Pope Life Center
University of Miami Miller School of Medicine
7:00 am Breakfast
7:45 am Solomon Terner: Welcome address
8:00 am William Vainchenker: “New Science in Myeloproliferative Neoplasms”
8:30 am Alessandro Vannucchi: “Molecular Prognostication in Myeloproliferative Neoplasms”
9-9:30 am Audience question and answer session
9:30 am Tiziano Barbui: “How I Treat Polycythemia Vera”
10:00 am Francisco Cervantes: “How I Treat Essential Thrombocythemia”
10:30-11 am Audience question and answer session
11-11:30 am Break for coffee and biscuits
[[[[***11:30 am Ayalew Tefferi: “How I Treat Myelofibrosis”*******]]]]
12:00 pm Johacim Deeg: “Who Do I Transplant and How”
12:30-1 pm Audience questions and answers
1-1:30 pm Lunch
1:30-2 pm Steven Nimer: “How I Treat Leukemic Transformation”
2-2:30 pm Swati Goel: “Review of Current Clinical Trials in Myeloproliferative Neoplasms: What’s The Professors’ Take On It?”
2:30-4 pm Panel discussion with audience questions and answers on all topics
4 pm Adjourn
Honestly with due respect, Tefferi announced a **Patient Conference** (see below) and did not specifically say anything about announcing further Imetelstat Mayo results **only** at this April 12 meeting which is more targeted at patient and family support. I have thoroughly searched the MPN forum and the internet for any other Tefferi statements about April 12 and as there are none, I cannot support your conclusions.
"Tefferi announced and invited everyone to his April 12 patient conference in Miami. According to Dr. Tefferi no drug companies have been invited or allowed to participate in any sponsorship of the event. He and others on the panel will be reviewing all clinical trials. He said he will ask the other Doctors there who will be presenting their findings the following question: “Would you put your daughter or son on this clinical trial.”
End2, I recall recently reading that Myelofibrosis patients who had to have red blood cell transfusions had **significantly worse survival** compared to those without transfusions. Also I remember that this paper stated that RBC transfusion-dependency had an independent prognostic impact on survival in multivariable analysis.
The reason I mention this is that your #2 topic mentions the need for a surrogate endpoint for overall survival. Based on the prognostic significance of becoming transfusion "independent" .....certainty it is within the realms of possibility that for Myelofibrosis patients who are chronically transfusion dependent.......... and after Imetelstat obtain transfusion independence....Geron will have a reasonable surrogate endpoint for overall survival. (Thus, potentially greatly shortening the trial duration as you mentioned.)
Mruyog I hear you and you certainly are an altruistic person for bringing up unapproved drug use for those who have no hope of survival. What I think are referring to is **Off-label** use. This would be the use of Imetelstat for an unapproved **indication.** The difficulty, in my opinion, is that for Imetelstat there is No approved **indication** or FDA sanctioned use for any disease for Imetelstat yet…. except for those tightly regulated and protocol driven entities we know as clinical trials.
If, let’s say for example… the FDA approved antibiotic Amoxicillin, was shown in the lab to somehow inhibit pancreatic cancer… then based on a physician’s best knowledge she/he could incorporate Amoxicillin for Off-label pancreatic cancer use. This would generally be legal unless it violates specific ethical guidelines or safety regulations. In addition, Off label use does carry tremendous health risks due to unknown variables. The physician can also get caught in legal liability entanglements.
Until Imetelstat is approved for at least one disease, off label use, I think, is premature. Geron also needs to stay laser focused on Imetelstat for Myelofibrosis and related blood diseases now until that **Indication** is either FDA approved or a large pharmaceutical company either partners with or buys Geron.
Bio that sound feasible and Burkchett (the author) states in her final discussion on Imetelstat and pancreatic tumor cells that ".... once telomerase is inhibited in a patient’s tumor, a **maintenance dose given once every other week** might therefore be sufficient to maintain continuous telomerase inhibition, thereby reducing the risk of side effects."
From the Mayo study and the ET study; it was demonstrated that a dosage of Imetelstat once every two weeks is within safe margins for most patients.
Bio I don’t recall seeing that in this study but I came across an estimate for the average cell doubling time of pancreatic cancer from another study by Amikura et al….. of 2.3 days.
A study emerged in Jan **2014** showing yet another possible treatment where Imetelstat could fill an unmet medical need and provide a therapy where none exists or is better than any available therapy. Today if you are diagnosed with Pancreatic Cancer the Prognosis is very poor in that 80% of patients will not be alive after one year.
Pancreatic cancer has one of the ***highest rates of recurrence*** following surgical resection. To me this study suggests that Imetelstat could block the regrowth of residual disease and prevent recurrences.
The aim of the below study was to define the effects of long-term Imetelstat exposure on the maintenance of telomeres and lifespan of pancreatic cancer cells. Most of the 10 Pancreatic Cancer cell types tested with Imetelstat had very short telomeres (2–3 kb in size). GRN163L inhibited telomerase in ***all*** 10 pancreatic cancer cell lines.
Imetelstat resulted in an initial rapid shortening of the telomeres followed by the maintenance of extremely short but stable telomeres. Continuous exposure to Imetelstat eventually led to Cancer Cell crisis and to a complete loss of Cancer Cell viability after 47 cell doublings. Crisis In these cancer cells was accompanied by activation of a DNA damage response and evidence of both senescence (cancer cells stop dividing) and apoptosis (cancer cells die).
Investor expectations need to be tempered by the fact that this is an initial laboratory study and **Not** a clinical trial.
Telomerase Inhibitor Imetelstat (GRN163L) Limits the Lifespan of Human Pancreatic Cancer Cells
Katrina M. Burchett, Ying Yan, Michel M. Ouellette
Published: January 07, 2014
The 33 abstracts for telomerase is now not surprising since telomerase research is following an almost exponential growth pattern. It was not that long ago when there were only a handful of telomerase projects going but today I was taking a look at telomerase in Harvard's medical database and came up with 9880 papers on it.
I'm with you there.
Since the upcoming trial is also International in scope, the upcoming results will be very hard to ignore by both the scientific and financial worlds.
From Hematology Times 12/13/13
“The drug works,” Dr Tefferi said. “It works at reducing the spleen [36% of patients had a greater than 50% decrease in palpable spleen or liver]. It works in relieving symptoms [77% had symptom response].”
“This is what JAK inhibitors can do, and this is not why we did the study. We did the study to see more disease-modifying activity.”
The team saw that 67% of patients experienced a complete resolution of thrombocytosis. Eighty-three percent of patients with leukocytosis had a more than 50% reduction of white blood cells, and 58% of patients had complete resolution of leukocytosis.
Forty percent of patients had complete resolution of leukoerythroblastosis, 36% had complete resolution of increased serum LDH, and 18% had reversal of bone marrow fibrosis.
“When you take everything all together, we had a complete or partial response of 23%, **which has never been seen with any drug,**” Dr Tefferi said."
"Overall response was defined as having a complete response, partial response, or clinical improvement. Forty-one percent of patients (n=9) met these criteria. "
Although "old news" as defined by message board standards... I don't recall seeing this particular article discussed or reading Tefferi's exclamation "The Drug Works"
Even after a few months I am astonished by the efficacy of Imetelstat for MF. (Yes I know... small sample size...even so thousands and thousands of small sample drug studies happen and results like Imetelstats are exceedingly rare.)
Ayalew Tefferi, MD's next presentation is the Scripps’ 34th Annual Conference:
Clinical Hematology and Oncology 2014 in San Diego California
2 p.m. Sunday Feburary 16 2014
Myeloproliferative Disorders: JAK2 and Beyond
Everyone here has a pretty good idea what the **Beyond** will be about.
Yes I had a hard time finding that too. Google Eastern Virginia Medical School 2nd Annual Hematology Conference and then click on the link to the brochure.
Wish I could go.
2ND ANNUAL HEMATOLOGY CONFERENCE
Saturday, January 25, 2014 • 8:00 am – 12:15 pm
Hilton Virginia Beach Oceanfront • 3001 Atlantic Avenue • Virginia Beach, Virginia 23451
11:15 AM Myeloproliferative
Neoplasma 2014: Science & Practice
Te¬fferi Ayalew, MD