I have had PV Jak2 V617 positive for 4 years and just entered PV study RG7388 for Idasanutlin.

[zocario]

I am currently a patient participating in cycle 2 of the trial RG7388 Idasanutlin. I am currently 43 years old. Diagnosed 4.5 years ago through BMB, Jak 2 V617F positive. At about 3.5 years a significantly increased symptom burden was interfering with work, and quality of life. At the start of the trial I was MF factor 1, splenomegally, increased reticulin fibrosis, completely iron deficient, high RBC, platelets consistently above 520, elevated basophils and elevated uric acid. Due to my relatively younger age, my Hematologist did not think a long term treatment involving Hydroxyurea would be the best option. I took HU for one month, was intolerant and started moving toward entering the study group for Idasanutlin. I am currently in Day 3 of Cycle 2. End of cycle 1 showed no improvement in spleen size, symptom burden nor in blood counts/ platelets. From what I have read, most patients in the study generally do not see any results until after cycle 3 with the longest showing improvement after cycle 16. The hardest part of Idasanutlin is the GI tox, which I will admit is a bit difficult. 2 days before I started cycle 2, I started a bland diet as it seemed to help the end of cycle 1. So far, cycle 2 has been a little easier than 1 but i honestly cannot say it is easy. It is pretty tough to add GI tox when you are already dealing with crushing symptom burden. My advice to anyone looking into the Idasanutlin study would be to start the process as soon as possible if you are already dealing with any symptom burden. I am convinced the symptom burden will not ever improve without some form of medication. Unfortunately all of these meds have side effects and it would be much easier to work through these side effects without the additional struggle of PV/ MPN symptoms. If anyone needs more information on how I ended up here, let me know and I will fill in any blanks. Sometimes, some of us who have been struggling with increased symptom burden, inadvertently leave out some of the details that may pertain to others. If any of you have interest in my ongoing experiences with this study, please let me know and I will try to update each month.

[Aneliv9]

I would like to ask you about the MF1 grade and reticulin fibres.. Is MF1 normal for PV patients? Also.. How increased were the reticulin fibres?? Slight increase, or more?

[zocario in reply to Aneliv9]

Yes PV patients can present a MF grade anywhere from absent 0 to 3. In my BMB report it states mildly increased reticulin fibrosis. I have had a concern about transformation to MF for quite some time and most doctors cannot tell me how post PV MF is positively diagnosed compared to just PV. Doctors tell me that I am low risk for transformation, but what are the indicators present?

[Aneliv9 in reply to zocario]

In the MF scale from 0-3, you can't have above grade 1. Cause 2 and 3 is Myelofibrosis i think.. but in the scale 0-4, grades 3 and 4 indicate myelofibrosis... in what scale was your BMB? Also "Mildly Increase" is the same as "slightly increased"?? Sorry but i am from Europe and I don't understand exactly the difference

[zocario in reply to Aneliv9]

My MF Grade 1 was based on the 0-3 scale. I also had read that grade 2 and 3 was Myelofibrosis, but my heme/ onc has showed me a study that examined the MF grade in 1233 PV patients, 20% were grade 0, 40% were grade 1 and the remaining patients diagnosed as PV were grade 2 and 3. This had added to my confusion about transformation to MF. I was able to find that grade 1 is not MF so for the time being I am going to accept current diagnosis of PV. However, the recently increased symptom burden is still worrisome.

[Aneliv9 in reply to zocario]

Ok. He is the doctor, so everything is fine! Although i am confused about pure PV with grade 2 or 3! I was sure that these grades were "post-PV MF" keep this site/ post updated about the clinical trial you are in. One more question if you don't mind.. RG7388 os only for those with Jak2 mutation? Could you make it clear??

[mhos61]

I think any feedback we have about MPNs, their treatment, clinical trials, side effects of medication etc is most helpful, so a huge thanks for posting.

I hope by you taking part in this clinical trial it will prove to be worthwhile eventually.

Please keep us updated, and best wishes

Mary

[Paul123456]

Thanks for the update

I think all of us would be grateful for ongoing updates. The RG7388 Phase 1 study appeared very encouraging and has sparked considerable interest into MDM2 inhibitors. As I posted last week, reducing MDM2 (which when raised inhibits our anti cancer fighting p53) sounds like a smart move.

I hope it works for you and the symptom burden reduces soon

Best Paul

[Joprv]

Hi Zocario, firstly my heart goes out to you.....

I am most interested in what you have shared about your challenges. It was most comforting to see you offering to advise others with broader explanations of your journey so far. I often feel that if I advise more of what I have been through (and it continues to escalate) that it may have a negative impact on others that are still learning to understand and accept the many variables that this group of insidious diseases can have. I am not sure on how to go about sharing the hard stuff, I would never want to upset/scare anyone as we are all so very different in how we cope with these difficult distressing matters. It is very important to stay as positive as possible especially given some 80% of patients NEVER actually progress or worsen.

After 6 years of PRV JAK2 + and now 2 years of post PV advanced (progressive) Myelofibrosis (with Thrombocytopenia) I feel like I too am now nearly as knowledgeable as some medical practitioners and have a great deal to share. I too am happy to share if anyone has any questions.

I would appreciate learning of your symptoms, what treatments you have tried and remain on; and what your Docs have to say about current status etc..

Hoping to learn more, sending you blessings,

Jo from Australia.

[neela2020 in reply to Joprv]

Hi, feeling nice to read your thought that you would like to share the problems of others.

I am 47 and have been diagnosed recently for PV. On hydra since then, still waiting for a right dose. every week CBC. I want to ask you that is it normal to have slightly elevated WBC and platelets for PV patient? Initially RBC was little high, and platelets in range , after a week break of hydra , it revesed. WBC keeps @ 12000 ( plus minus every week )

[Lena70 in reply to neela2020]

Hi neela2020. I just saw this post. I have PV JAK2+. I am not on hydra, currently on aspirin, so I'm not sure if my reply will help.

Besides high platelets, I also have very wonky white blood counts. I have high leukocytes, high eosinophils, and high basophils. Did you have out of range white blood counts at the time of your diagnosis?

[neela2020 in reply to Lena70]

my WBC are always between 11 to 13 ..keep fluctuating every week.

After being on hydra my main problem is when RBC comes close to lower level, platelets are little high and when Platelets are within range RBC goes bit high. HB and MPV is good.

[Wyebird]

Thank you for taking the time to post. I’m ET Calr but you never know my future pathway

[Chaz1]

Thanks for sharing my hubby has ET/PV Jak2 + and increased reticulin fibrosis which we were told at the time is to be expected with the diagnosis. He turns 49 next week & thankfully not had any thrombotic events. He was diagnosed because he was so symptomatic & the blood tests led quite quickly to the diagnosis. His consultant constantly states that symptoms are unrelated and he now doesn't work as struggling with fatigue, bone pain & brain fog, and with out much support it's been our only option. He was referred to Chronic Fatigue Clinic as Haemo said fatigue wasn't MPN but the clinic disagreed and so advised him to reduce his hours to try & manage & have a work life balance. Would be interested to hear your progress in the trial going forward as looking for options for Hubby. Sending positive thoughts

[Anag]

Hi Zocario, I’ve used the AutoImmune Paleo diet, supplements, getting optimal levels of nutrients, hormones and vitamins/minerals balanced in my body, exercise, especially breathing, detox, getting rid of heavy metals in my body, etc. I’ve gotten rid of nasty allergies, intolerances, fatty, sluggish liver, brain fog, most of my fatigue, eczema, splenomegaly, 18.5kg of stubborn fat, and depression that plagued me my whole life. I have 1 mill thrombos w/o Anagrelid. With 3x 0,5mg Anagrelid, I’m around 600. there’s a lot one can do outside nasty meds. I take the one that is necessary and a bit of aspirin and all else is natural, to make sure my body and brain is relieved of any unnecessary burdens. There are no longer chemicals in my house in it on my body. My ET has hardly gotten worse in 2 years, since I took other measures, only my heart has palpitations when more than 3 Anagrelid. This summer was turbulent, but it seemed there was something wrong with my pills and I got a new box. All ok now. Good luck with this treatment! Thank you for giving us this information. Cheers. Anag

[harleydavidson]

Hi Zocario. Just want to wish you luck with your trial. Mel x