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Pegylated Interferon Therapy Demonstrates Efficacy and Durability for Treatment of PV and Essential Thrombocythemia

 

Pegylated interferon alfa-2a (pegylated interferon) demonstrated durability and viability for the treatment of polycythemia vera (PV) and essential thrombocythemia (ET), according to phase 2 study results presented by Lucia Masarova, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, at the 66th ASH Annual Meeting.

Previous research has investigated long-term data on the use of pegylated interferon for the treatment of PV, however research is limited on the use of pegylated interferon for the treatment of ET. To explore this, researchers conducted a single center, prospective, phase 2 trial on pegylated interferon use for the treatment of both PV and ET.

Masarova and colleagues concluded, “Our phase 2 study proves pegylated interferon as a viable and durable treatment option for patients with ET and PV.”

Transcript:

Hello, I'm Lucia Masarova from MD Anderson Cancer Center in Houston, Texas, and I'm presenting updates from ASH 2024 here in San Diego on our studies here. We have a phase 2 study of pegylated interferon alfa-2a, or Pegasys, using patients with essential thrombocythemia and polycythemia vera, which is a long-term update of our phase 2 study that first started in early in patients in 2005. The study terminated last year, and this analysis focuses both on the separate diseases after a long-term treatment based on the different responses as well as the molecular background.

The study enrolled 40 patients with essential thrombocythemia and 43 patients with polycythemia vera. The current analysis [is] basically dissecting them separately and looking at how would the outcome or the therapy be dependent based on different drivers for ET. ET is essential thrombocythemia, about 60% of these patients could be JAK2 mutated, about 30% could be calreticulin, and the rest are either triple-negative or MPL [(myeloproliferative leukemia virus oncogene)].

In this study, out of the 40 patients, 19 were JAK2-positive, 9 were calreticulin, and then 9 were triple-negative. The rest were MPL. We basically wanted to see how the responses and duration would differ between the calreticulin patients and the JAK2, because there's more evidence about interferon working on the malignant clone from the JAK2. But there's also some disputable results about, will patients with calreticulin derive similar benefit, lesser benefit or more benefit?

The overall duration of therapy was not different based on these different drivers. So calreticulin patients were treated equally long for almost 19 months and a median treatment duration was similar across all groups. Actually, only JAK2 patients that did not have a molecular response, which was defined as a decline in JAK2 allele burden by less than 20%, had the shortest duration of therapy, only about 40 months. Everybody else was on therapy for 90 months or more.

Interestingly, the dose didn't differ. We have seen 100% hematologic responses in calreticulin-mutated patients, and only 1 of these patients lost the response during the therapy while on interferon. Interestingly so, also 5 of these 9 patients that were calreticulin were able to be on therapy for more than 5 years, and 2 of these patients were actually on therapy for more than 15 years and only stopped therapy because it was terminated last year and are still continuing on Pegasys off therapy. That was something that we interestingly seen because it was lower in JAK2-mutated patients.

Then interestingly, there was the time to start. Patients with calreticulin were treated the earliest, about 14 months median time from diagnosis, which was more than 40 or 50 months for JAK2 or other subtypes.

In the calreticulin group as well, we have seen about similar rates of thrombosis, but we have seen much more progression to myelofibrosis even on therapy, which is aligned with the current data. These patients do tend to progress faster. Interestingly, they progress on interferon, so there needs to be maybe more exploration, whether it was dose dependent, they were just not receiving dose, there wasn't enough in the long term, and so and so. A small cohort, but interesting observations.

For PV patients, we have looked at the different characteristics based on the molecular response. We divided based on complete molecular remissions, or patients that would achieve undetectable or level of sensitivity detectability of JAK2, and then what we call partial remission, which is more than 20% but less than a 100% or 99%. And then non-responder would be less than 20% or non-evaluable.

For this analysis, we have published results before in 2017 in the Lancet Hematology. With this update, which was interesting to see, that the patients that achieved the lowest JAK2 allele burden or the most decrease, called “CMRs,” had been the youngest, median age was only 44 years, whereas the other patients were 55 or more. They were also studied on therapy, the earliest only 4.7 months from the diagnosis to treatment. Everybody else in a JAK2-mutated PV started on therapy with median of 60 months.

That's a striking difference, which tells us more that we may need to treat these patients earlier, the younger age where we could do more, because these patients definitely tolerated therapy the longest. We have not seen differences in achievements of complete hematologic responses, however, a patient that achieved lower than complete resolution of the JAK2 clone, such as molecular response, had more relapses. So 67% of these patients lost their achieved response versus only 1 of the 7 CMR patients. The longer we were able to decrease the JAK2 burden, the better for us.

There were no other differences in terms of provoked or unprovoked events in these patients or the duration of therapy. These patients were treated also quite very long. There was a very interesting update, which we will put together as a publication, and it actually closed our phase 2 study.

 


Source:

Masarova L, Bose P, Pemmaraju N, et al. Phase 2 study of pegylated interferon in patients with essential thrombocytopenia and polycythemia vera: final analysis focused on the two diseases. Dec 7-10, 2024; San Diego, CA. Abstract: 1807 

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