Ruxolitinib Retains Benefit in Polycythemia Vera With Longer Follow-Up

Responses to ruxolitinib (Jakafi) in patients with polycythemia vera were maintained by a majority of primary responders at 4 years’ follow-up.

Responses to ruxolitinib (Jakafi) in patients with polycythemia vera (PV) were maintained by a majority of primary responders at 4 years’ follow-up, according to an updated analysis of the RESPONSE trial presented at the 2017 ASH Annual meeting.1

The response persisted in three-fourths of primary responders at 208 weeks. Additionally, 70% of patients who had clinicohematologic (CLHM) response maintained that status. There were no new safety signals compared with the previous follow-up at 80 weeks.

“Patients with polycythemia vera who were resistant to or intolerant of hydroxyurea [Hydrea] had durable hematocrit control and clinicohematologic response,” said Jean-Jacques Kiladjian, MD, PhD, head of clinical investigation at Saint Louis Hospital in Paris. “Taken together (with the safety data), these results support ruxolitinib as an effective long-term treatment option for patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.”

The RESPONSE trial randomized patients with PV and hydroxyurea resistance or intolerance to ruxolitinib or best available therapy. The trial had a composite primary endpoint of hematocrit control plus at least a 35% reduction in spleen volume at week 32.2

The primary analysis showed that 21% of 110 patients assigned to ruxolitinib met the primary endpoint, as compared with 1% of patients assigned to best available care (P <.001). Response to ruxolitinib was similar in patients who had hydroxyurea intolerance (22%) or resistance (20%).

The long-term analysis of safety and efficacy at 208 weeks was specified in the RESPONSE trial design and follow-up continues, noted Kiladjian.

RESPONSE randomized 222 patients to ruxolitinib or the control group. At 208 weeks, 41 patients (37%) originally randomized to ruxolitinib remained on treatment (median exposure 225 weeks), as compared with none of the patients allocated to the control group (median exposure 34 weeks). Kiladjian reported that 37 of 98 patients (38%) who crossed over from the control arm to ruxolitinib after 32 weeks remained on treatment. Additionally, 32 patients (29%) assigned to ruxolitinib completed 32 weeks of treatment versus 1 patient (1%) in the control group.

Durability of efficacy was the principal outcome of interest for the 208-week analysis. This included the primary endpoint and the prespecified secondary endpoint of CLHM, defined as hematocrit control, platelet count ≤400 x 109/L, and white blood cell (WBC) count ≤10 x 109/L. Overall survival was an exploratory endpoint.

Results at the 208-week landmark showed that 19 of 25 patients who attained primary responses to ruxolitinib at 32 weeks maintained those responses. The absolute numbers translated into an estimated probability of 0.73 maintaining primary response. Analysis of the separate components of the primary endpoint yielded an estimated probability 0.73 (95% CI, 0.60-0.83) for maintaining hematocrit control and 0.86 (95% CI, 0.61-0.95) for maintaining spleen-volume reduction.

The median duration of response had yet to be reached among patients who attained a primary response at 32 weeks, Kiladjian noted.

The estimated probability of maintaining CLHM remission at 208 weeks was 0.54 (95% CI, 0.31-0.72). Of 87 patients with WBC >10 x 109/L at baseline, 42 (48.3%) achieved WBC count ≤10 x 109/L at 208 weeks. Of 54 patients who had a platelet count >400 x 109/L, 26 (48.1%) had a platelet count ≤400 x 109/L at 208 weeks.

The 70 patients who attained CLHM at 32 weeks had a probability of maintaining that response of 0.67 at 208 weeks. Kiladjian reported that 21 of the 70 patients had progressed during long-term follow-up. The median duration of CLHM response had yet to be reached, he added.

The exploratory intention-to-treat analysis of estimated 5-year survival yielded values of 90.6% (95% CI, 80.1%-95.7%) for ruxolitinib and 87.7% (95% CI, 74.8%-94.3%) for the control arm, not accounting for crossover to the ruxolitinib arm from the control group. Kiladjian pointed out that no patient in the control group remained on assigned therapy at the time of the 80-week analysis.

Hematologic adverse events (AEs; all grades, irrespective of causality) occurring most frequently in the ruxolitinib arm included anemia (9.3%; 1.0% grade 3/4) and thrombocytopenia (4.6%; 1.0% grade 3/4). Infection was the most common nonhematologic AE, occurring in 19.6% of patients in the ruxolitinib arm (3.7% grade 3/4). The next most common types of events were pruritus (7.3%), diarrhea (7.1%), headache (6.1%), arthralgia (5.9%), weight gain (5.6%), muscle spasms (5.2%), and fatigue (5.1%).

Two on-treatment deaths occurred in the ruxolitinib arm since the week-80 analysis (gastric cancer and unspecified malignant neoplasm, neither considered related to treatment). Additionally, 4 on-treatment fatal AEs occurred among patients who crossed over to ruxolitinib, but none were considered related to treatment with ruxolitinib.


  1. Kiladjian JJ, Verstovsek S, Griesshammer M, et al. Results from the 208-week (4-Year) follow-up of RESPONSE trial, a phase 3 study comparing ruxolitinib (Rux) with best available therapy (BAT) for the treatment of polycythemia vera (PV). Presented at: 2017 ASH Annual Meeting; December 9-12, 2017; Atlanta, GA. Abstract 322.
  2. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426-435. doi: 10.1056/NEJMoa1409002.