Discussion
death, pruritus, thrombotic
ADVERSE EVENTS, EVENTS, DISEASE, THROMBOEMBOLISM
In this futility analysis, we analyzed interim data to decide whether enrollment of pts with untreated PV into the randomized Ruxo-BEAT trial is safe and effective. The futility analysis showed significant improvements for Hct, JAK2V617F allele burden, and pruritus. Moreover, there was a significant reduction in the number of phlebotomies. Consequently, the trial was recommended to be continued by the Data Monitoring Committee.RUX treatment was well-accepted by patients, as indicated by the lack of dropouts in the first 6 months of treatment among the patients analyzed so far. Also, there were no new safety signals of adverse events of RUX treatment, when compared to those already described in the RESPONSE [Sustained control of hematocrit levels is of major importance in PV pts, in order to decrease cardiovascular mortality (death from cardiovascular reasons or major thrombotic events) [The continuous measurement of JAK2 allele burden during therapy is an interesting means of non-invasive disease monitoring, albeit not yet clinical routine, as the consequences of the results and guidelines on how to act on changes are still lacking. In the RESPONSE trial, significant decreases in JAK2 allele burden due to RUX treatment were reported [RUX significantly reduced pruritus in our cohort. This is an important finding, since pruritus in PV may severely reduce the quality of life and is often not sufficiently treated by other drugs [This pre-specified analysis has certain limitations: due to the short time of RUX treatment and the low patient number, we have not yet studied whether there was any effect on the rate of thromboembolism. This will be important to analyze at later time points during the trial. Also, more abundant information on complete blood counts and symptoms will then need to be analyzed. Finally, since it is important to assess how RUX treatment compares to BAT in this cohort of untreated PV pts, a comparative analysis will be performed in the interim analysis and the final analysis of the trial.First-line treatment of PV is rapidly evolving, particularly with the recent approval of ropeginterferon, and it will be interesting to evaluate whether RUX proves beneficial in the first-line setting. Also, the question of optimal second-line treatment after ropeginterferon is currently unclear but may involve RUX treatment. Finally, while cytoreductive treatment in PV is not currently recommended for low-risk PV pts, Barbui and colleagues [In conclusion, the futility analysis of the RuxoBEAT trial confirms that treatment with RUX in untreated PV pts is effective (regarding the above-mentioned endpoints), feasible, and well-tolerated. The trial is currently ongoing.