Differences in Clinical Outcomes Between Hydroxyurea-Resistant and-Intolerant Polycythemia Vera Patients

[PhysAssist]

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients

ABSTRACT

Background: Previous studies have suggested that patients with polycythemia vera (PV)

who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct

characteristics and clinical outcomes. However, to date, no studies have reported a

comparison between these two groups or assessed prognostic factors in these patients.

Methods: The objective of this study was to evaluate clinical outcomes and identify

prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV

patients who received frontline treatment with HU from nine centers and identified 90

patients with HU-R or HU-I.

Results: The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and

the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups,

the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P =

0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%,

P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for

progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83–21.47, P = 0.003).

Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and

prior thrombosis were identified as unfavorable predictors of overall survival.

Conclusion: These findings suggest that patients with HU-R face a higher risk of

hematological transformation, but have a comparable risk of thrombosis to patients with HU

intolerance. These distinctions should guide decisions on second-line treatment options and

clinical trials involving these patients.

Source: jkms.org/pdf/10.3346/jkms.2...

[EPguy]

Thanks for the new info. It supports an older study, below, so the result has been reproduced.

healthunlocked.com/mpnvoice...

The plot here from the current report shows a large added risk with HU-R, with hazard ratio (HR) of 6.27, which is surprisingly close to the HR of 7 that I recall from that long ago post. The message is if HU isn't working within the first year, try a different therapy, although the comment on pages 7 and 8, below, indicate a continuing handicap.

Unfortunately for Koreans, where this study originates HU is the only option: "This was due to limited second-line treatment options for HU-R/I patients in Korea, as ruxolitinib and interferon use were restricted by the National Public Health Insurance Service."

On pages 7- 8 they seem to find that HU R/I negative effects carry through in pts on Rux or IFN. "Remarkably, this secondary analysis yielded congruent results to those obtained when analyzing the entire study population." If so these pts may expect a lower effectiveness on any of the current therapies. They offer a possible explanation: In previous research "HU-R in PV patients was associated with the acquisition of non-driver genetic mutations, implying a higher likelihood of disease progression".

MFS-HU-R Differences in Clinical Outcomes PV

[PhysAssist in reply to EPguy]

Hi EPguy,

1) de nada- When I come across a study that seems relevant or helpful, I try to remember to bring it here to share.

2) You really provided an excellent context and as you note, seeing results replicated certainly adds credence and validity to the reported results. Your analysis of their reporting is also very helpful.

3) Your ability to remember and curate/collate the vast amounts of information presented here and elsewhere on MPN's is astounding to me, and very helpful to all of us- so thank YOU, and keep up the excellent work!

Best,

PA

[EPguy in reply to PhysAssist]

Assembling random bits of history is a big part of being a good inventor. But I'm not sure how much longer it will hold as Sjogren's corrodes me.

It's interesting to compare the actual plot from the early 2012 report, seen here. Data are inverted but the similar trend is clear. I just noticed how much longer the time scale is in the 2012 report, so we know there's no copying of data. The HU-R end points seem the same while the newer report got there much faster (a more negative outcome). The 20 year scale of the 2012 report could be esp relevant to the long term IFN studies if HU-R status were tracked.

MFS