Ruxolitinib

[waddles22]

Husband has PV and MPN currently on Ruxolitinib which for him has been amazing and life saving. Only drawback is having had some skin cancers. Presently he has a lot of sores on head and face that will not clear and having problems with doctors not recognising that these sores and scabs can yet again be cancerous. Additional risks with taking Ruxolitinib can be associated with it. Haematologist is very understanding though. Anyone else have similar concerns. Thanks

[Orangeboykitty]

The danger of skin cancer was one of the reasons I stopped taking Jakafi. It's a known side effect of that and also HU. I started on Jakafi originally because I needed to shrink my spleen quickly and it did that. But after about a year it stopped working on my PV symptoms and they all came back. So with the risk of skin cancer always on my mind, I decided (with my hematologist's blessing) to switch to Pegasys. Now on Besremi, which is working well and doesn't promote skin cancer. BTW - I live in the Negev Desert in Israel where we have blazing sun during many months of the year.

[ainslie]

My understanding about Rux and skin cancer is that although it mentions it in the leaflet it is maybe not clear that Rux is actually the culprit. I discussed the topic with a Rux expert at MDA Houston before starting it. His opinion then (2017) was that it was not clear Rux was the cause , most people go to Rux because HU was no longer effective ie a lot of previous HU use, HU is known to cause skin cancer. I read that maybe Rux patients who have heavy sun exposure in the past can get skin cancers, so it may be a grey area. Personally I am on Rux 5 years and I had low UVB therapy daily for 10 years for PV itch , I have fair skin and my mother had melanoma, I was on UVB and Rux for 4 years and I get my skin checked every 6 months, so far it’s perfect. But I have never taken HU and cover up in sun,plus hat and SPF 50 have a UV meter to check UV levels on holiday, no sunbathing, I am under the umbrella , ie very careful. My personal view is it’s a grey area , however the data may have changed but I have not read that anywhere.

[MichaelS in reply to ainslie]

I had an email from healthinlocked referring me here.I was on HU for nearly 30 years after being diagnosed with PVR in 1983. I switched to Rux in 2013 because a BMB showed it had changed to MF in 2010. I started getting skin cancers on the face and scalp in 2018, some 5 years after starting Rux, hence I think it's the Rux that's caused them, but my haematologist doesn't agree. I will be seeing a MPN specialist in early July who knows of the skin cancer connection with Rux. The Rux had controlled bloods and spleen very well and I think that is why my haematologist is reluctant to change my drug, after all this time.

Best wishes everybody and try to keep smiling, from Michael

[ainslie in reply to MichaelS]

thats a interesting history Michael, I wonder if you had skin cancers when you were on HU only, there does seem quite a lot of skin cancers when Rux follows HU , I also wonder if there wasnt previous HU use if you would still have got the skin cancers on Rux, it will be very interesting to hear what your derm has to say in June, perhaps you could post if you feel okay with sharing it.

[MichaelS in reply to ainslie]

No I didn't have skin cancers until 5 years after I started Ruxolitinib. I did have Rosecea on the face, which disappeared within days of starting Ruxolitinib.

[EPguy]

This is a recent study (2021) on the subject.

It shows a significant Rux connection to "nonmelanoma skin cancers (NMSCs)"

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For certain skin cancers the odds were more than 3X as likely on Rux but it depends on the skin cancer:

<<In patients with PV or MF with ruxolitinib exposure, the adjusted hazard ratio (aHR) for NMSC was 2.69 ... For squamous cell carcinoma, it was 3.24 ...; and for basal cell carcinoma, there did not seem to be an increased risk for ruxolitinib-exposed patients (aHR, 1.60; ....>>

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<<The risk of squamous cell carcinoma appeared to be worse for ruxolitinib-exposed patients with non-JAK2-mutated disease >>

This implies MF has higher risk vs PV since the study includes only PV and MF, with PV being almost always Jak2. A different version of this study summary confirms that PV still has a signif added risk.

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About 1 year is typical for the skin cancer to appear, with a range of 0.2-5 years :

<<median time to a first NMSC diagnosis after treatment initiation of 66.5 weeks (range, 11 to 245).>>

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<<HR for NMSC with an immunosuppression history was 5.39 (95% CI, 1.34-21.61).>>

That is a very high risk. Immunosuppressives include many other cancer treatments, organ transplant drugs, as well as Rux to an extent.

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oncologynurseadvisor.com/ho...

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Rux also adds risk for immune response (covid etc)

<<It works by weakening your body's defense system (immune system). >>

reference.medscape.com/drug...

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My Dr favors me using Rux, rather than the Besremi I am on. I am having it rough with Bes so far so the relief on Rux even with above issues is tempting.

[ainslie in reply to EPguy]

HiDo you have the name or link of that 2021 paper please?

I am curious to read if those patients had a lot of HU exposure pre Rux or not. As previously mentioned when discussing the subject with Dr Verstovsek at MDA back in 2017 he was of the view that it wasn’t clear that Rux alone was the culprit as many Rux patients had heavy previous HU use which is known to cause skin cancers, I mean to consult wit him soonish about something else so will ask the question again to see if his view has changed.

[EPguy in reply to ainslie]

Sorry the link is placed late in the post. Here it is easier to find.

oncologynurseadvisor.com/ho...

This study was retrospective, usually less desirable than prospective. But its n was decent, 188 Rux and and 376 non-Rux patients.

I had an error in an important item, this part:

<<median time to a first NMSC diagnosis after treatment initiation of 66.5 weeks (range, 11 to 245)>>

Weeks not months, for a range of appearance of NMSC of about 1-5 years.

It could be Dr V has more info now, in 2017 Rux in use was still relatively new.

My Dr was involved in some of the Rux studies and considers it to be relatively low risk vs the other options. (INF in particular)

I agree HU exposure could be a factor, this study does not mention HU history.

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But I just found this one that seems to include HU history:

onclive.com/view/ruxolitini...

It looked for non-skin cancers and <<Ruxolitinib Found Not to Increase the Risk for Secondary Malignancies in Polycythemia Vera>>. But it did find <<a substantial proportion of non-melanoma skin cancer was seen with ruxolitinib treatment vs without...>>

So these two studies seem to point to possible non-melanoma skin cancer risks.

Let us know What Dr V says.

[ainslie in reply to EPguy]

Thank you for re posting that info, its very interesting, I have been on Rux for 5 years now and no skin probs to date, I also had daily UVB for nearly 10 years for itch (albeit low dose)which I would have thought would increase risk and my mother had melanoma. I have not been on HU though. Dr V has been using Rux for MF since 2008 and I think his first patient is still doing okay on it. Hence he has massive experience and I follow MPN.net which is mainly US and they tend to post all the latest papers and info on such matters so I think I would have heard if Dr V's view has changed but I will indeed ask him when I speak next. Keep up with the great posts.

[EPguy in reply to ainslie]

I think Dr V is experienced in both Rux and INF, is that right? My Dr also says Rux can work well for a long time. Like everything in these matters, each of us gets differing results and the reports don't tell how just one of us will react to therapy.

Dr V likely has reports that give different results than these, including his own clinical practice. It will good to hear his info.

[ainslie in reply to EPguy]

I think Dr V is more or was in to Rux than Inf, I asked him about a year ago what he thought about adding Peg or Besremi to my Rux as a combo for PV and he said not to. At that time he was not so convinced by Peg or Bes in term of affecting progression etc, he also said Bes is only one molecule different to Peg so unlikely to be much different. I will be speaking to him in next few months and hear what his latest views and data are. He said that he has not had any PV patients losing effectiveness with Rux in the same way that it can for some with MF unfortunately.

[EPguy in reply to ainslie]

Very similar to my Dr on the Rux point of view and on any combo with INF. There was a phase 2 study many of us have seen, below, on the combo and it worked ok, but it was for those who INF alone was not working vs just to add up the benefits. I would like to try this combo, I am having dissonance from Drs' opinions on Rux vs INF, and I have also heard here and read that Rux does work over time with PV, while as you say has limits for MF.

Between two MPN leaders it seems Dr V is toward Rux and Dr Silver is toward INF.

That single molecule seems to make a big diff for some members as in recent posts. Also I think it is many molecules that differ, the PEG type and attachment points, and the α-2a vs α-2b distinction of the INF that the PEG attaches to.

Look fwd to anything you learn from his latest views, esp if he has info on progression on Rux. It seems he may since he has a view on INF there.

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healthunlocked.com/mpnvoice...

[waddles22]

Many thanks to all comments concerning my post