Moving towards disease modification in polycythemia vera

[Manouche]

In this review, we provide an overview of the current and evolving treatment landscape of PV and outline our vision for a patient-centered, phlebotomy-free, treatment approach using time-limited, disease-modifying treatment modalities early in the disease course, which could ultimately impact the natural history of the disease.

sciencedirect.com/science/a...

[hunter5582]

Looks like it would be an interesting article. Were you able to access the full article?

[Manouche in reply to hunter5582]

Not yet! This is a pre-proof article, so the full version should be available soon.

[ainslie in reply to hunter5582]

If you click on the link and top right side Patient Access, amazingly they will e mail a copy , mine came in a few hours

[hunter5582 in reply to ainslie]

Thank you. I sent in the request.

[ainslie]

this is a good paper and written by well balanced experts inc John Mascarenhas , is one of the best. I have read the full paper and its good , one interesting point in it re Dr Silvers paper re Inf versus Hydroxy and alleging Inf giving longer MF free arrival , some reality in that is that it was a retro trial and the Hydroxy arm had 56% high risk patients wheras the Inf arm had only 26%, some what relevant , it also mentions that the Inf patients tend to acquire more mutations than on hydroxy, these points are not usually mentioned in the posts by the inf enthusiasts. They do a lot of good things about inf and I agree but the point is we have to be realistic and balanced , otherwise it gives misleading info to patients who may not be fully educated on their MPN as yet. Please note their conclusion below

"However, we would like to emphasize that the current

evidence does not support the general implementation of such an early, IFN-α-based

intervention strategy in all patients with low-risk PV. Longer follow up is necessary"

[hunter5582 in reply to ainslie]

I was able to access the entire paper. Thanks.

I agree that is is a reasonably balanced view about the different treatment options. The authors actually favor the use of the IFNs but also acknowledge many of the issues with current treatment options as well as limitations in the current data.

Given the absence of a disease-modifying treatment effect, the associated burden on patients and caregivers, and the development of novel, alternative approaches, the role of phlebotomy as the primary and exclusive treatment for patients with low-risk PV is diminishing. Additionally, the use of hydroxyurea as the default choice for cytoreductive therapy is debatable especially with the approval of novel IFN-α formulations that are better tolerated and could offer an attractive option for a broad range of low and high risk patients. Increasing evidence suggests that IFN-α has the potential to change the natural history of PV with deep (and sometimes durable) molecular remissions in a subset of patients that may translate into an improved myelofibrosis-free and overall survival.

In summary, our current treatment approaches are inadequate to help PV patients live the longest and best life possible. Available therapies such as IFN provide an opportunity for patients with PV to achieve deep molecular responses as a surrogate for disease burden reduction, and the integration of mutational testing into the management of PV should allow us to delineate minimal residual disease states.

It is important that the authors suggest that mutational testing should be considered an endpoint in treatment and clinical trials. This is consistent with the emerging viewpoint amongst many MPN experts.

So, on the whole this paper is supportive of the use if the IFNs while maintaining a note of caution.. There is some excellent information contained in the tables that are at the end of the paper. It is important to read the whole paper to actually understand what the authors are saying. Illustrative quotes do not tell the whole of what the authors trying to convey.

Two of the important studies (my opinion) that the authors make note of are the LOW-PV and ECLIPSE PV clinical trials. Much more needs to be known in long-term studies of the use of IFNs with low-risk PV. I would predict that once the data on the data on low-risk PV is in, the evidence will support the viability of IFN for this group; however, no one should assume that is so without the long-term data. I am glad that the ECLIPSE PV study is underway. I am predicting that the data will not support the use of the more aggressive dosing strategy to attain a faster CHR - more effective molecular response. I think the toxicity profile of more aggressive dosing will not be favorable when we consider the risk/benefit balance.

The main point of this is that we need to base treatments protocols on data. We need agreed-upon endpoints for both treatment and clinical trials. The authors do a very good job of outlining this in the paper (see table 4).

As always, it is great to converse with my MPN friends and family. Wishing all of you all the best on your MPN journeys.

[monarch5000]

Those authors have a long history of being interferon skeptics and they continue to be as evidenced by their statement: "longer follow-up is needed to assess whether molecular responses associate with clinically meaningful outcome measures such as thrombosis and progression to myelofibrosis or AML."

It's 2023 and those Sloan-Kettering and MD Anderson docs are still not telling their patients that only interferon offers them the chance to attain a durable, potentially lifelong state of Minimal Residual Disease like these two docs have been doing since 2014:

.

[ainslie in reply to monarch5000]

Monarch

I am sorry but it has to be said what you have written is simply not accurate. The docs are not all from Sloan Kettering or MD Anderson. At least one is from Mount Sinai. If you read the paper they paint a pretty positive picture for the use of Inf but a realistic one. Similarly last night I was on a Zoom meting organised by LLS Leukaemia and Lynphoma Soc USA , it was called State of the Art Treatment, Future Advances, and Optimizing Nutrition for Myeloproliferative Neoplasms (MPN) . There were two docs from Mount Sinai one of which was one of the authors of the paper you posted and its worth a watch if you can find it , he painted a very positive picture of the use of Inf. The other treatments came up and interesting point came up they said the drop out rate for hydroxy was 20% , which is well known , I dont know where those Inf docs came up with 2.5% drop out for Hydroxy over 7 years, that alone questions credibility.