KEY TAKEAWAYS
- A phase 3b, open-label, randomized RESPONSE-2 trial assessed the efficacy of ruxolitinib in patients with polycythemia vera without splenomegaly who were intolerant or resistant to hydroxyurea.
- Evaluation of hematocrit control at week 28 was the primary goal. At week 28, patients with the best treatment option might switch to ruxolitinib.
- The secondary endpoints were evaluated at week 260, including durable hematocrit control, overall survival, and adverse events.
- Ruxolitinib showed superiority in achieving durable hematocrit control, and the median duration of hematocrit control was not reached.
After 5 years of follow-up, the RESPONSE-2 study found that ruxolitinib, a Janus kinase inhibitor, showed superiority over the best available therapy for hematocrit control in patients with inadequately controlled polycythemia vera without splenomegaly. Phase 3b research was conducted in 48 hospitals in 12 countries in Asia, Australia, Europe, and Canada. The trial enrolled patients aged ≥18 years with polycythemia vera without splenomegaly, who were either resistant to or intolerant of hydroxyurea and had an Eastern Cooperative Oncology Group performance status of 2 or less. Participants were randomly assigned in a 1:1 ratio to receive ruxolitinib or the best available therapy for up to 80 weeks, with ruxolitinib starting at 10 mg twice daily.
Patients initially assigned to the best available therapy could switch to ruxolitinib at week 28 if the primary endpoint was not met or after week 28 and up to week 80 if the best available treatment was ineffective or not tolerated. Patients who received ruxolitinib at week 80, including those who switched from the best available therapy, could continue treatment until week 260. The study evaluated secondary endpoints at week 260, such as durable hematocrit control, the median duration of hematocrit control, median hematocrit level over time, the number of phlebotomies, and overall survival, and analyzed the results based on the intention-to-treat principle. The patients were randomly assigned to receive ruxolitinib (n=74) or the best available therapy (n=75) for up to 80 weeks. At randomization, patients receiving the best available treatment were on hydroxyurea (n=38), interferon or pegylated interferon (n=9), pipobroman (n=5), lenalidomide (n=1), or no treatment (n=22). During the study, 58 (77%) of 75 patients in the best available therapy group crossed over to ruxolitinib between weeks 28 and 80, and 97 patients received ruxolitinib until week 260. The 22% (95% CI 13-33) of the patients in the ruxolitinib group had durable hematocrit control at week 260. In contrast, the best available therapy group’s patients’ median duration of hematocrit control was not recorded since there were so few responders by week 80. Median hematocrit level among patients in the ruxolitinib group remained below 45% during the 5-year follow-up, and 60 phlebotomies were required among 74 patients in the ruxolitinib group in 260 weeks compared to 106 phlebotomies among 75 patients in the best available therapy group in 80 weeks.
The ruxolitinib group had a 5-year overall survival rate of 96% (95% CI 87-99), while the best available therapy group had a 5-year overall survival rate of 91% (80-96). The most common grade 3-4 adverse events (exposure-adjusted per 100 patient-years) in the ruxolitinib group and best public therapy group were hypertension (8 [2·4%] vs. 3 [5·6%]), thrombocytopenia (1 [0·3%] vs. 3 [5·6%]), and thrombocytosis (0 vs. 4 [7·5%]). Exposure-adjusted rates of any-grade thromboembolic events were 1·5% per 100 person-years (5 of 74 patients) in the ruxolitinib group and 3·7% per 100 person-years (2 of 75 patients) in the best available therapy group. Throughout the research, there were no deaths reported.
The RESPONSE-2 study’s 5-year findings indicate that ruxolitinib is a favorable second-line treatment option for patients with polycythemia vera without splenomegaly who have insufficiently controlled their condition.
Source: https://pubmed.ncbi.nlm.nih.gov/35597252/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02038036
Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomized, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. doi: 10.1016/S2352-3026(22)00102-8. Epub 2022 May 18. PMID: 35597252.
