Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach

[Manouche]

 »In regard to PV, the decision to introduce cytoreduction may be more understandable than in ET. Even young patients with PV are exposed to a higher risk of thromboembolic complications with respect to ET.19 Additionally, a recent publication showed that the cumulation of CV risk factors in PV patients, independent of age, has a negative impact on OS.20 Treatment recommendations underline that all patients with PV, regardless of age, should receive phlebotomy to reduce hematocrit (Hct) below 45%, based on the results of the CYTO-PV trial.21 However, the risk of symptomatic iron deficiency and logistic problems in real-life settings encourages the physician to introduce cytoreduction, even in low-risk patients, as a more reliable approach to managing Hct and minimizing the possibility of complications. Therapeutic dilemma in low-risk PV is debated.22, 23 On the other hand, the justification for introducing cytoreduction in ET patients is not as understandable. Findings similar to those presented in this study have been observed for young patients with ET, with 1 study highlighting that cytoreduction is given willingly in patients with ExT1000, despite a comparable distribution of CV risk factors and lower incidence of AT.16

Recently, Abu-Zeinah et al. presented a database analysis of 40,333 MPN patients followed between 2001–2017. The authors confirmed higher mortality in young PV and ET patients in comparison to the healthy population of the same age. Furthermore, the study revealed a significantly higher excess of all-cause mortality in young (<60 years of age) MPN patients with respect to the older (≥60 years of age) population of MPN patients.24 The authors indicate that this excess mortality may be the result of undertreatment within the group of young and potentially low-risk patients with MPNs. However, those observations are based on a database analysis that does not include the data regarding treatment, with the assumption that patients are treated strictly according to the guidelines. If findings from our study could be extrapolated to worldwide practice, and similar trends shown in numerous studies suggest that they could, this higher excess mortality may not be a result of undertreatment but rather overtreatment or improper treatment. In both our study groups and in the literature, HU is the most frequently used cytoreductive agent.16, 17, 20 There is an abundance of warnings regarding the use of HU in younger patients, resulting mainly from uncertainty concerning its leukemogenicity and the possibility of the development of a second malignancy.5, 25 This threat was further acknowledged by Abu-Zeinah et al. in their study of excess mortality, where the authors reported an unacceptably high degree of cancer death in young patients with MPNs.24 Nonetheless, each patient should be evaluated individually, and if the physician qualifies for cytoreduction, the use of different agents needs to be considered. Anagrelide is a potent cytoreductive agent available as a second-line treatment for patients with ET.26 However, reports of inducing bone marrow fibrosis should be taken into consideration.27 Alternatively, ruxolitinib is an attractive therapeutic option for symptomatic patients with PV. However, its use is limited to patients with confirmed refractoriness to HU.28, 29 Finally, peg-IFN and ropeg-IFN represent the best alternatives for PV and ET patients, allowing them to limit the hazards of extended cytoreduction, avoid exposure to iron deficiency, achieve molecular remissions, and possibly prolong OS.30, 31, 32, 33, 34, 35, 36 Nevertheless, due to limited accessibility, none of our patients were treated with the use of this agent as the first-line therapy. »

advances.umw.edu.pl/en/ahea...

[Mishie14]

WOW. Facinating read, thank you very much Manouche for sharing. Raises some interesting questions and challenges some accepted practices. Curious to see if change to treatment strategies will result.

[DeKa]

Thank you for sharing. Many of us have our own stories of completely inappropriate, hare-brained schemes, to treat PV, for which there is zero literature to support.

[saltmarsh]

Thanks for the info. Much appreciated.

[ainslie]

it’s good to see this data coming from Polis haems, I havnt seen much from Poland re haematology, I hear medical care is of a high standard there.

One point to correct in the article , they say Rux is good but is limited to those who are refractory to HU, that may well be the case in Poland but as this is a international forum it’s important to say that patients in many countries can get Rux even if they have never tried HU, eg me.

Regarding whether to treat PV at diagnosis with meds or venisection only. There is a debate on that exact subject at the doc to doc conference in New York in October, at this conference there are hundreds of the worlds top docs there every year. I understand the debate is with Hans Hasselbach and John Mascerenhas , the latter from Mount Sinai. I plan to be there, should be interesting.

[RoundTheWorld in reply to ainslie]

Ainslie do you know if the conference is going to be streamed online for a wide audience? Sounds like it could be interesting.

[ainslie in reply to RoundTheWorld]

I don’t know for sure, usually the main talks are if you subscribe , not sure about the debate though, also sometimes they change the speakers etc at the last minute.

[RoundTheWorld in reply to ainslie]

Thanks Ainslie. I've just spent an educational half hour listening to the Onclive Insights discussions between John Mascarenhas and Joe Scandura. Really interesting stuff.

[ainslie in reply to RoundTheWorld]

JM is a expert expert, well respected by other experts.