Can HU and IFN-α be combined?

[SouthSideA]

Greetings, MPN family.

I switched from HU to IFN-α this past July. I did so in hopes of benefiting from the disease modifying properties of IFN-α. At diagnosis my JAK2 VAF was 46%. After a few months of HU treatment, it fell to 19%. A month after switching from HU to IFN-α it was at 24%. My doctor tells me that the difference between 19% on HU and 24% on IFN-α is insignificant, and we need to give the IFN-α more time.

A few questions for this knowledgeable community:

How long does it usually take for IFN-α to really work and to meaningfully drop the VAF value?

Since my VAF also dropped on HU, is there any evidence that HU could be MORE effective than IFN-α in controlling VAF?

Is there any evidence that a combination of HU and IFN-α e makes sense and effectively controls counts and lowers VAF?

Thank you, in advance, for any thoughts on these questions.

[ainslie]

typically HU can lower AB quite quickly for a year or so but can then go back up again, INF is more a slow burner but more durable for some, INF time to lower AB varies a lot , it can even take a couple of years for some to get complete control of counts on INF. combining the two meds is technically possible but rare. If you tolerate the INF well then probably wise to hang in there.

[SouthSideA in reply to ainslie]

Got it. This is helpful. I will give the INF time. My counts look good, and I will trust it’s slowing the progression of the disease. Thank you for taking the time to reply!

[hunter5582]

As ainslie notes, the evidence is that while there can be a temporary reduction in VAF with HU, the VAF eventually will rebound. The IFNs impact on VAF has been shown to be more enduring and deeper. It is true that HU has a more rapid effect on cytoreduction. The IFNs are more slow acting, I look at MPN treatment as being a marathon, not a sprint. Since prevention of progression (using VAF as one of the biomarkers) is a primary treatment goal for me, relying on the IFNs (Besremi) makes sense in my situation. Besremi is also working better for me than HU and is much easier to tolerate.

While it is possible to combine HU with an IFN, it is not a common practice. There is an increased risk of side effects and drug interactions. It is not something I would be comfortable with in most situations. This is really a question for a MPN expert doctor who can give you the best advice based on your profile.

Wishing you all the best.

[SouthSideA in reply to hunter5582]

Many thanks for yet another thoughtful reply!

[dbus1417]

I am currently on a combination of interferon and hu, but we are in the process of reducing and removing the HU. I am taking 1 X 500mg HU every other day, down from 2x 500mg daily. While we have been reducing the HU I have started interferon at 45 mcg weekly and am currently injecting 135 mcg weekly.

My blood counts are controlled pretty well using this transition method with no side effects to speak of. I had some mild liver irritation around the 90 mcg mark but my liver numbers have started to return to normal at 135. All bloods are in range with the exception of platelets just under 600.

I see my hematologist in January to make the decision to get off the HU if everything looks good.

[SouthSideA in reply to dbus1417]

Thanks for this reply. It's good to be in touch with someone who is also making the HU-to-IFN transition. I'm a few months ahead of you, having begun the switch in June. I've gone from 2 x 500mg HU daily to 500mcg IFN every two weeks. As you likely know, this is the full dose of Besremi which many people have trouble tolerating, but I've been fine. Please keep in touch about your experience. I'm hopeful this switch is the right thing for both of us.

[dbus1417 in reply to SouthSideA]

For what it’s worth - CALR type 1, 41 yo male

[SouthSideA in reply to dbus1417]

In a 44 year old male. Good to be in touch with someone my age. Let’s keep in touch.

[Exeter21]

Interferon took a good 18 months to get a settled result. I had a great MPN expert so I did not get concerned with slow or no movement as we got doseage correct. My bloods all now within range & steady. I take 45 monthly now . You cannot rush Interferon. HU may be quick but the side effects I had on it were horrendous & so glad I got Interferon . 👍

[SouthSideA in reply to Exeter21]

Great to know that it's working well for you. I'm at a full dose of 500mcg every two weeks, and my counts look good. I don't know about my VAF, but I'm hoping this will drop over time. Good luck to you, and please keep in touch.

[Exeter21 in reply to SouthSideA]

I was a bit heady at beginning but lower dose stopped that. Lots of water helps & a walk. Also I inject morning as overnight felt heady morning 👍 Julia UK

[Jamesxyz]

That's an excellent question.

I don't believe there have been any studies with both meds together.

I can see one situation where a low dose oh HU combined with IFN might be beneficial.

If the patient has trouble controlling hct with a tolerable dose of IFN but everything else is good.

A low dose of HU might do the trick and might be preferable to lots of tps.

Just my 2 cents.

[SouthSideA]

thanks for this!

[EPguy]

This is the familiar plot from the Besremi trials, with an approx result for you overlaid in blue. I assumed a "few" months on HU was about 3 months. "Control" in gray is HU. If so you can see you did better than the median gray line in the Bes trial. A good start. But you see as others have posted here, HU effect on VAF is rarely durable, something like just 1% get durable molecular response as I recall.

Light blue is the small increase you had on IFN, But one month is not enough to know any trend as your Dr said. The light blue circle at bottom is about where you are now at 6 months of IFN.

"How long does it usually take for IFN-α to really work and to meaningfully drop the VAF value?" --- If your blood counts are responding odds of molecular response are better than if bloods were not responding, and at 6 months a trend might show up. Is your Dr ok to do VAF tests more frequently? Why did you get the test at 1 month?. My Dr did a few during my 11 months on IFN.

Your good response to HU is evidence you're not resistant, this is a good thing prognostically as I've posted. But if IFN is holding the counts adding HU back in is unneeded extra risk for the standard MPN goal of controlling blood counts. As noted by others, HU and IFN are typically combined only during the transition.

HU appears initially "more effective" in this trial, being steeper than IFN, but effect is not durable. I may have had a similar head start on VAF as I was on HU for 15 months. But I have no VAF for that time.

There is a combo that has been trialed and some members are on , IFN+Rux. But this is not commonly offered nor needed. In hindsight I might have been a candidate.

SouthSideA

[SouthSideA]

This is extremely helpful! Thank you. I will be patient and give IFN time to work. I should have mentioned that I am currently taking 500 mcg of the Besremi (the full dose), and my counts look good: WBC is at 3.5; platelets are at 170; hematocrit is at 40. Because of this, my doctor's inclination is to continue the Besremi at the full dose to get the maximum benefit. Does this sound like the right approach to you?

[EPguy in reply to SouthSideA]

My Dr did the same on dosing. In my case it was 140 limited by lymphocyte. What is your lymphocyte result? If it's not called out separately you should request the test that does, in the US it's called "cbc with differential"

The "maximum benefit" usually refers to reducing the VAF aggressively, that is why my Dr directed what was a high dose for me. But it may follow that any adverse outcome risk is also higher with a dose greater than required for safe PV blood counts (CHR). For example a dose that holds HCT 43-44 and PLT to <400 meets the normal requirement for MPN treatment. Patience you note is a good thing. I could have held CHR on 50-70mcg.

You ask my opinion, I'd request to lower the dose to just that required to hold blood counts, and, separately, at least to hold a safe min lymphocyte. Liver counts also are a factor. Taking the "whole bottle" is aggressive when you're already well under the blood count goal. I'm biased by a one-of-a-kind bad outcome that probably would have been avoided with the minimum dose for CHR strategy.

The various trials have found a correlation of achieving CHR and reducing VAF. Does more IFN than required reduce VAF more? I've not seen any data that points to that, but some Drs do follow this. Other members may have some reports.