Posthydroxyurea cytoreductive therapy

In the phase II MPN-RC 111 study (NCT01259817), 50 patients with PV received pegylated interferon alfa-2a. Patients had previously received hydroxyurea and had either an inadequate response or unacceptable side effects.[12]

In the phase II MPN-RC 111 study (NCT01259817), 50 patients with PV received pegylated interferon alfa-2a. Patients had previously received hydroxyurea and had either an inadequate response or unacceptable side effects.[12]

The complete response rate was 22%, and the partial response rate was 38%. A total of 14% of patients discontinued treatment because of side effects.[12][Level of evidence C3]

In the open-label RESPONSE study (NCT01243944), patients with phlebotomy-dependent PV and palpable splenomegaly were randomly assigned to receive either ruxolitinib or standard therapy (interferon, pipobroman, anagrelide, immunomodulators, or no treatment/phlebotomy alone). Patients had previously received hydroxyurea but had either an inadequate response or unacceptable side effects.[21]

In the open-label RESPONSE study (NCT01243944), patients with phlebotomy-dependent PV and palpable splenomegaly were randomly assigned to receive either ruxolitinib or standard therapy (interferon, pipobroman, anagrelide, immunomodulators, or no treatment/phlebotomy alone). Patients had previously received hydroxyurea but had either an inadequate response or unacceptable side effects.[21]

Ruxolitinib was superior to standard therapy with regards to phlebotomy-free control of hematocrit (60% vs. 20%; P < .001), reduction of spleen volume (38% vs. 1%; P < .001), and reduction in symptom score by 50% (49% vs. 5%; P < .001).[21][Level of evidence B3]

The follow-up open-label RESPONSE-2 study (NCT02038036) included 173 patients with phlebotomy-dependent PV without palpable splenomegaly who had either an inadequate response to or unacceptable side effects from hydroxyurea. Patients were randomly assigned to receive either ruxolitinib or best-available therapy (interferon, pipobroman, anagrelide, immunomodulators, or no treatment/phlebotomy alone).[15]

The follow-up open-label RESPONSE-2 study (NCT02038036) included 173 patients with phlebotomy-dependent PV without palpable splenomegaly who had either an inadequate response to or unacceptable side effects from hydroxyurea. Patients were randomly assigned to receive either ruxolitinib or best-available therapy (interferon, pipobroman, anagrelide, immunomodulators, or no treatment/phlebotomy alone).[15]

Hematocrit control was achieved in 62% of patients who received ruxolitinib and 19% of patients who received best-available therapy (hazard ratio [HR], 7.28; 95% CI, 3.43‒15.45; P < .001).[15][Level of evidence B3]

MAJIC-PV was a phase II study that randomly assigned 180 patients to receive either ruxolitinib or best-available therapy. Patients had experienced an inadequate response or unacceptable side effects from prior hydroxyurea therapy. Patients remained on study for up to 5 years without crossover.[22]

MAJIC-PV was a phase II study that randomly assigned 180 patients to receive either ruxolitinib or best-available therapy. Patients had experienced an inadequate response or unacceptable side effects from prior hydroxyurea therapy. Patients remained on study for up to 5 years without crossover.[22]

At 1 year, the complete response rate was 43% for patients who received ruxolitinib and 26% for patients who received best-available therapy (odds ratio, 2.12; 90% CI, 1.25–3.60; P = .02).[22][Level of evidence B1]

MAJIC-PV was a phase II study that randomly assigned 180 patients to receive either ruxolitinib or best-available therapy. Patients had experienced an inadequate response or unacceptable side effects from prior hydroxyurea therapy. Patients remained on study for up to 5 years without crossover.[22]

Thromboembolic event–free survival was significantly higher in the ruxolitinib group compared with the best-available therapy group (HR, 0.58; 95% CI, 0.35–0.94; P = .03).