Cancer Treatment Today

Currently, the only therapy approved for second-line treatment of high-risk PV is ruxolitinib. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) trials enrolled patient who were resistant or intolerant to hydroxyurea, required phlebotomy every 3 months, had palpable spleen with MRI-confirmed volume of over 450 cm3, and platelet count of less than 100,000. Patients were randomized 1:1 to ruxolitinib at 10 mg twice daily (n = 110) versus BAT (n = 112). There was a primary composite end point of hematocrit control in the absence of phlebotomy and 35% or more spleen volume reduction (SVR35) at week 32 in the RESPONSE trial.

In RESPONSE-2, patients did not have splenomegaly and did not require SVR35 as an end point. The end point in this trial was assessed at week 28.

There were 21% of patients who achieved the primary composite end point in the ruxolitinib arm versus 1% in the BAT arm (OR, 28.64; 95% CI, 4.50-1206; P < .001). Separately, SVR35 was seen in 38% of patients receiving ruxolitinib and 1 patient receiving BAT; 60% and 20% achieved hematocrit control, respectively.

The RESPONSE-2 trial confirmed data for hematocrit control, with 62.2% of patients given ruxolitinib achieving control compared with 18.7% given BAT (OR, 7.28; 95% CI, 3.43-15.45; P < .0001).

After 5 years of follow-up for the RESPONSE trial, 83% of patients on the ruxolitinib arm did not require phlebotomies. There were 41% with normalization of leukocytosis and 46% with normalization of thrombocytosis. There was a 67% 5-year probability of maintaining clinic-hematological response and 72% 5-year probability of maintaining SVR35.

In the ruxolitinib arm, the rate of thromboembolic events was 1.2 per 100 patient-years, 8.2 in the BAT arm, and 2.7 in patients who crossed over from BAT to ruxolitinib. Ruxolitinib also improved rates of second malignancies or nonmelanoma skin cancer compared with BAT but did not improve rates of transformation to myelofibrosis and acute myeloid leukemia, according to Passamonti.

Aschenbrenner DS. New Treatment for Polycythemia Vera. Am J Nurs. 2022 Mar 1;122(3):18-19.

Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208.

Mora B, Passamonti F. Polycythemia Vera: Is it Time to Rethink Treatment? Presented at: Society of Hematologic Oncology 2021 Annual Meeting; September 8-10. Accessed September 9, 2021