Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial

Abstract

RESPONSE-2 is a phase 3 study comparing the efficacy and safety of ruxolitinib with the best available therapy (BAT) in hydroxyurea-resistant/hydroxyurea-intolerant polycythemia vera (PV) patients without palpable splenomegaly. This analysis evaluated the durability of the efficacy and safety of ruxolitinib after patients completed the visit at week 80 or discontinued the study. Endpoints included proportion of patients achieving hematocrit control (< 45%), proportion of patients achieving complete hematologic remission (CHR) at week 28, and the durability of hematocrit control and CHR. At the time of analysis, 93% (69/74) of patients randomized to ruxolitinib were receiving ruxolitinib; while in the BAT arm, 77% (58/75) of patients crossed over to ruxolitinib after week 28. No patient remained on BAT by week 80. Among patients who achieved a hematocrit response at week 28, the probability of maintaining response up to week 80 was 78% in the ruxolitinib arm. At week 80, durable CHR was achieved in 18 patients (24%) in the ruxolitinib arm versus 2 patients (3%) in the BAT arm. The safety profile of ruxolitinib was consistent with previous reports. These data support that ruxolitinib treatment should be considered also as a standard of care for hydroxyurea-resistant/hydroxyurea-intolerant PV patients without palpable splenomegaly.Electronic supplementary materialThe online version of this article (10.1007/s00277-018-3365-y) contains supplementary material, which is available to authorized users.

The Myeloproliferative Neoplasm Landscape: A Patient’s Eye View

“…Improved QoL was also seen compared with standard therapy in patients with PV and splenomegaly and an inadequate response to or intolerance of hydroxyurea [43,44]. In addition, durable improvements in haematocrit and symptoms in patients without splenomegaly have been observed [45]. On the basis of these trials, ruxolitinib has been widely approved for the treatment of splenomegaly or symptoms in patients with MF (PMF or MF secondary to PV or ET) and for patients with PV who are resistant to or intolerant of hydroxyurea, and it is recommended, generally, as a second-line treatment option, in most treatment guidelines for PV (Table 1).…”

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review

“…Since its inception in 2011, long-term surveillance of ruxolitinib has shown a durable clinical response, stable symptomatic control, and a survival advantage in patients with MF and PV. 1,2,4,9 However, accumulating data indicates an association between the immunosuppressive capability of ruxolitinib and a heightened risk for developing infections. This is the first study utilizing FAERS in order to assess the potential risk of developing MTB and AMI in ruxolitinib-treated patients, and the results of this analysis suggests that patients on ruxolitinib are at heightened risk of developing MTB and AMI.…”

“…[1][2][3] In patients with PV with either inadequate response or intolerable adverse effects from hydroxyurea, ruxolitinib has demonstrated improved control of hematocrit and reduction of splenic volume compared with standard therapy. 4,5 Despite being a successful treatment option, data suggests an increased risk for infections owing to associated immunologic derangements. Reports of reactivation of pulmonary tuberculosis and disseminated infections in patients treated with ruxolitinib are accumulating, and this is included in the drug package insert.…”

Thromboembolic events in polycythemia vera

“…In the primary analysis of RESPONSE-2, the corresponding rates were 1.4% ( n = 1) with ruxolitinib and 4.0% ( n = 3) with BAT [ 70 ]. At 80 weeks of follow-up in RESPONSE-2, embolic and thrombotic events occurred at a rate of 1.5 per 100 patient-years in the ruxolitinib group and 1.9 per 100 patient-years in the BAT group [ 73 ]. This finding may be attributed to better HCT and WBC control with ruxolitinib than with standard therapy, given that these 2 hematologic parameters have been independently linked to an increased risk of thrombotic events [ 13 , 28 ].…”

“…In the primary analysis of the RESPONSE studies, the proportion of patients who achieved HCT control (i.e., ≤ 45%) was significantly higher with ruxolitinib than with BAT (RESPONSE, 60.0% vs 18.8%; RESPONSE-2, 62.0% vs 19.0%) [ 69 , 70 ]. HCT control was also maintained in most patients (RESPONSE, 73% for 208 weeks; RESPONSE-2, 78% for 80 weeks) [ 71 , 73 ]. Additionally, in both RESPONSE studies, the proportion of patients undergoing phlebotomy procedures was lower with ruxolitinib than with BAT.…”