Ruxolitinib Provides Better Efficacy Than Best Available Therapy in Polycythemia Vera

[Manouche]

« Patients with polycythemia vera (PV) achieved greater hematocrit control and improvement in symptoms with ruxolitinib compared with best available therapy (BAT), according to the results of a systematic review and meta-analysis published in the journal APMIS. Ruxolitinib was also associated with higher rates of nonmelanoma skin cancer, anemia, and certain infections »

hematologyadvisor.com/news/...

[EPguy]

A good summary.

"Among patients with hydroxyurea-resistant or intolerant PV, higher rates of CHR (RR, 2.28...);" For pts for whom HU is not working, it is 2.3x more likely to get CHR on Rux. HU resistance is a negative prognostic as discussed in old posts, so Rux is a good alternative.

On the non-melanoma risk, "a higher rate of nonmelanoma skin cancer in the ruxolitinib group compared with the BAT group (RR, 3.82...") This points to greatly enhanced risk (~4X) over HU assuming HU was a large part of BAT. (they don't specify how many of each BAT) This is a surprise and invites comments.

Rux was better for thromboembolism, more than 2X as likely on BAT vs Rux.

The anemia risk does not make sense since this can be addressed in PV by dose reduction as ainslie has noted in the past. Only explanation would be dose being set for WBC or PLT control.

--

This is likely one of the studies included, which may be the 1st to show specific benefit of molecular response in PV :

healthunlocked.com/mpnvoice...

[ainslie in reply to EPguy]

Where you write the skin cancer risk is 3.82 increased on Rux, I’m maybe a bit sceptical , I have read it’s allegedly increased, is it 3.82 in the original paper, I think it says something about 30% of the Rux group were failures on Hydroxy, hence they were probably on high dose Hydroxy prior perhaps for a long time. This where these summary articles although interesting don’t give the whole picture compared to the original papers written by haems.

[jon1972]

Thanks for this post. I just started Rux about 3 months ago and am interested in this data. I'm very concerned about the non melanoma cancer risk. I don't know much about it or how dangerous it is, but I got burned a lot when I was young and have a lot of sun spots and such so I feel I'm already at a higher risk.

[EPguy in reply to jon1972]

Melanoma is a more serious category, but non-melanoma includes some harsh ones too.

This (worst) case study is an example:

pmc.ncbi.nlm.nih.gov/articl...

with this recommendation:

"we advise skin screening 2 to 3 times a year for all patients under treatment. Even in the absence of a history of NMSC, (Non-melanoma) if skin tumors develop during or after JAK-I therapy, we recommend more frequent dermatological monitoring, up to 4 times a year."

Merkel cell carcinoma is a rare but high risk NMSC that has been seen with Rux.

This retrospective study found a hazard ratio (HR) of 3.24 for SCC skin cancer for those on Rux. And for non-Jak2s ie CALR etc, HR was 7.4. Both are high, but still relative to a rare event.

pubmed.ncbi.nlm.nih.gov/346...

None of the reports I see state the dosage used. But as with IFN, it suggests the min effective dose is best.

In normal conditions I'd be low skin risk, but this report does motivate for more frequent derm checks and self inspection for anything unusual. In your case frequent checks are likely a good idea.

We're lucky to have treatments (my other disease has none) but better ones are needed. The INCB160058 in trials is one hope.

healthunlocked.com/mpnvoice...

[jon1972 in reply to EPguy]

Thanks for that info EP. You're on Rux too right? What dose are you on? I was started at 10mg but it's starting to look like I might need to be upped. 135mcg of Peg wasn't enough to control my bloods so I wouldn't be surprised if I require the max on Rux. Looks like I'll be making my next dermatology appt sooner than I planned

[EPguy in reply to jon1972]

I'm at 10BID. (20/day) since Apr 2023. I'm hoping to go lower at next Dr visit, if my low end range RBCs continue down. You could be right that higher IFN need predicts higher Rux need, but I know of no study or other experience here to compare. I needed just 50-70 of Bes to hold counts (but Dr insisted on 140, with a very bad outcome) HU was 500/day.

Could be my declining VAF is helping reduce dosage, again no way to know and I'll hope to find out soon whether VAF is still going down.

[ainslie in reply to EPguy]

Again on that Pub med article it doesn’t even mention previous hydroxy use which is very relevant, were the patients only ever on Rux or were they failed Hydroxy first, it’s another example of where the summary is possibly misleading.

When you say it suggests the min effective dose is best, it depends what that means, I’ve never heard that before for Rux. It may seem logical and may be correct but maybe not.

What does min effective dose mean with Rux or inf. or is it better to have a bit more than the min effective dose in the hope that it may (for a subset) reduce allele burden or reduce it faster and possibly slow progression. My expert at Mount Sinai has no problem with my high dose ie 22.5+20, my Hct is around 40 so I might do on a bit less Rux but my AB is according to latest Mount Sinai labs at 1.08 allegedly. ( it was allegedly 14 from the UK lab in Oct but that was part of a NGS which Mount Sinai say is not as accurate as just testing Jak2 only, that’s for another post though). Minimum effective dose is a bit of a grey area perhaps, generally less drugs the better but sometimes higher doses with Rux or Inf might do the big job better ie treating the MPN, assuming there are no problems with low counts or side effects. I get it some people are more prone to immunity and skin issues.

[EPguy in reply to ainslie]

Agree detailed info is missing. BAT includes Rux but they don't say what % of the BAT cohort. Since HU is a common BAT it should be a signif portion with which Rux was compared. Their inclusion of pipobroman and non-peg IFN points to some very early studies. It would be helpful to see the detailed data the OP study used.

You're doing really well on Rux at your dose, so it makes sense. My history suggests HCT near or below 40 makes me droopier, a pattern that held with HU and IFN. But you bring up a good point, while the IFN studies tended to dose being not correlated to VAF reduction, Rux studies offer no such analysis. Getting CHR on IFN has a good correlation to VAF reduction, maybe this holds for Rux too. If there are studies with this variable it would be good to see. But VAF reduction is only recently being published for Rux so that study may come later.

The relation of Rux to skin cancer is consistently showing up, and we see it on the forum. Prior HU use may be a factor, but if so many pts will have this history. If the OP study details separated the HU pts we could see this effect more directly. Assuming this risk is real, less dose should be better. But as you say, regular checks can reduce this risk. Vs IFN, Rux is less prone to severe surprises of any kind.

I had a good continued VAF reduction on my 10-10 dose. I may find out soon if it continues. I've had good CHR on all 3 drugs.

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On your Jak2, were both via blood draw? Look fwd to your notes on that huge difference.

[Quitojohn in reply to jon1972]

ask a dermatologist to check you once a year or so

[ainslie in reply to jon1972]

I am now on Rux 22.5+20 , I started in 2017, my skin so far is perfect, I get a derm to check it every 6 months, I did UVB phototherapy for 10 years daily prior to Rux, I do avoid direct sun on holiday and cover up and use factor 50, I am fair skinned and my mother died from melanoma yet I have had no skin cancers. I have not been on Hydroxy. My expert at Mount Sinai is of the impression that Rux doesn’t cause skin cancer, he reckoned previous hydroxy use or sun damage were the culprits, I have heard from other expert haems re the previous Hydroxy view. Personally I wonder if it’s a bit of a grey area. I see an expert dermatologist, he said that the key is to get very regular quality skin checks and that most skin cancers if caught EARLY are usually very fixable. He recommended 9 months for me but I go every 6 months. My advice to anyone is check, check, check.

[jon1972 in reply to ainslie]

Sorry for the dumb question, but what does 22.5+20 mean?

[ainslie in reply to jon1972]

22.5mg in morning and 20mg in evening, fair question I should have made it clearer

[saltmarsh]

Thanks for this post

[ainslie]

thanks for posting this, no doubt there is some excellent info in there, this is written by an independent author as opposed to written by the people who did the trials ie the haems, I wonder if when it’s a independent author for a publication if they tell it as the haems would have, maybe but maybe sometimes not, that’s not a criticism just my observation having read other articles by independent authors. It’s also a pretty short summary of a “meta analysis” , did I read it right that it was on 1000 patients which is low if they call it a meta analysis, apologies if I didn’t read it thoroughly enough.

[EPguy in reply to ainslie]

I agree, at least we should get access to the details it was based on to understand it better.

[Bongo63]

thanks a really interesting article, I’ve been on Rux since Pegasys and Hydroxy didn’t lower my HCT, since I’ve been on Rux my levels are a lot better at 33. I am a little anaemic but we are looking at this at my next appointment . I do have a question though should I see a dermatologist as it’s not something I’ve been advised before.

[EPguy in reply to Bongo63]

What dose of Rux are you on? 33 is quite a change from over limit on IFN/HU

Derm checks are a good idea for anyone on Rux. Also the Shingrix vaccine is advised.