The results in our study demonstrate that the new dosing regimen of 250-350-500 µg of ropeginterferon alfa-2b is well-tolerated and highly efficacious in patients suffering from PV. This dosing regimen was associated with a rapid achievement of CHR without the need for phlebotomy or erythrocyte apheresis. The CHRs were very durable and the levels of CHR were numerically greater than previously reported for the slow-titration dosing schema. This was also accompanied with a high level of JAK2V617F allelic burden reduction. The results suggested that treatment of patients with PV at this dosing regimen of a higher starting dose and simpler intra-patient dose titration can eradicate the mutant cell clones carrying the driver mutation JAK2V617F in PV in a more efficient manner.
It will be interesting to see if this finding is replicated. I am doubtful about the viability of the more aggressive dosing schedule for all MPN patients. Given that there are those of us who cannot tolerate even the starting dose of 250mcg, While I remain very pleased with my overall response to Besremi, I think that that the low-and-slow approach is safer. I would hypothesize that there will be greater acceptance and successful use of Besremi with a more conservative approach. Time and data will determine how the field moves forward.
It's a good outcome. They allowed only HU intolerant/resistant pts. This limitation was not part of the Proud PV trials and suggests a harder to treat cohort.
The idea in this study was to escalate dosing by large fixed increments without regard to response, rather smaller increments as required for response at clinician's discretion in Conti PV.
Median dose here was 800/month (400/2weeks), in ContiPV is was 500 (250/2weeks)
If members here are representative, from my subjective impression, and Hunter's thought also, 400/2weeks is much more than most are using, and would be tolerant of. Even 250 seems high. I don't think a majority of members could tolerate doses of 400, any comments welcome. As known to regulars, I had an extreme permanent and devastating AE on 140.
In a now dated post, below, I surveyed members early in Bes use, and we were using quite small doses. Could be this plot now would look very different, or the Voice members are self selected for a different response. Both may be true.
They made a connection of CHR to VAF reduction: "It also appeared that most patients with a greater reduction of the JAK2V617F allelic burden experienced CHR." This pattern has been seen in most studies. Conti PV found a strong such correlation, while dose was not well correlated to VAF in that study.
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Fig 2 in the present study is the plot relating to "CHR was maintained in 29 patients (59.2%)" I've seen this sort of loss of response in other studies I think for both IFN and Rux. It suggests 40% lost response, while the authors call the response "very durable". Looks like "reasonably durable" to me, a subjective judgment.
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This study was from China. Another is ongoing in Korea. A third larger one is ECLIPSE:
is testing the high dose against the current standard. It should be the best comparison since there is a control. But it's formally for only 24 weeks, so they are well focused on quick CHR. But they show a 48 week point in the sponsor's page. Still no measurement of VAF, a top concern of their customers. Interesting they will be checking marrow.
Probably worth mentioning "A Qin, O Zagrijtschuk, and T Sato are employees of PharmaEssentia Corporation. DX Wu, WH Shen, W Wang, JJ Zhang, and YN Li are employees of PharmaEssentia Biotech (Beijing) Ltd." for what it's worth.
Maybe dose doesn't matter that much.
Here's another study that showed 100ug for 24 months did the job.
The Conti PV study and others did find dose did not well correlate to VAF reductions, while CHR does in various prior reports.
This report has:
"This value (VAF reduction) is roughly the same as that obtained after 24 months in the PROUD-PV/CONTINUATION-PV studies, which used a much higher ropeg dose (average of 425 μg)...and this was particularly evident in patients with baseline VAF greater than 50%."
Stronger effect on higher VAFs is seen also in this plot from an early study I've posted on. The low VAFs were for ET but the present study supports the idea more broadly. It likely relates to zygousity as discussed in detail a couple years ago.
There is a detail that may bias this VAF result :"The effect of ropeg on JAK2V617F allele burden was evaluated in responders..." Meaning only those who got HCT in range were included for VAF study. Excluding those without HCT (and thus CHR) would bias to better VAF effect. Proud PV did not exclude non-CHR pts I recall. In this context, having only 55% pts getting molecular response seems low.
There is a mention of high body mass being one negative response predictor, relating to need for higher doses. I've never seen this before.
In my case I did get a good response with low VAF, 14-8% on Bes for 11months. Rux has taken it to 5% last check. I'd trade all of it to be Sjogren's free.
Agree, selecting for both low risk and HCT responders is unusual and should give better VAF results. The ECLIPSE trial I noted should give meaningful comparisons.
Thank you for posting this. Interesting findings. Having been on Pegasys for over 18 months with little impact on the VAF (actually an increase from 79 to 86% !) , I am about to move to Besremi (at alternating 100 mcg and 50 mcg doses). CHR still not achieved with, lately, occasional venesections. Fingers crossed that Bes will prove more effective and that, with time, it will work its magic and knock out some of that clone!
While it is an interesting study, I would note several issues with the study.
The study is based on a relatively small (n=49) sample size of HU-intolerant patients all drawn from China. The authors contention that the results can be generalized to all people with PV is questionable. There appears to be potential sample selection bias that needs to be addressed through replication of the finding with a larger and more diverse population.
The tolerability of the higher dosing is difficult to evaluate without more data. The issue of Grade 2 Adverse Events (Moderate AEs that can significantly impact the patient's quality of life or necessitate medical attention) was not adequately addressed. There were a total of 13 Grade 3 AEs (Severe adverse effects are serious and potentially life-threatening reactions that require prompt medical intervention); though there may have been overlap in the actual number of patients who may have experienced more than one AE. I would not want to draw any conclusions about tolerability without knowing more.
The study also does not compare to previous studies demonstrating that CHR and reduction in VAF can be achieved at lower doses that are easier to tolerate. While it seems credible that treatment targets of CHR and VAF may be achieved more quickly at higher dosing, there is no evidence that the more rapid achievement of these goals has value. It is arguably not worth the additional risk.
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