The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis

Abstract

BackgroundAnemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35–54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.ResultsThirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration.ConclusionsConcomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009).

Ruxolitinib – better prognostic impact in low-intermediate 1 risk score: evaluation of the ‘rete ematologica pugliese’ (REP) in primary and secondary myelofibrosis

“…A lower need for transfusions was recorded in patients responding to ruxolitinib, together with a reduction of symptoms. An association of ruxolitinib to erythropoietin may be useful in this phase, as suggested in another report [15]; our experience shows that some patients become sensitive to erythropoietin following ruxolitinib. As regards the hematologic status, we modulated the dose of therapy according to the presence of anemia and platelets number; patients who received less than 40 mg/day of ruxolitinib had a significantly shorter duration of response even if the response rate was similar in both patients groups.…”

Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial

“…Although findings are preliminary, concomitant administration of erythropoiesisstimulating agents was well tolerated and did not have a negative impact on the efficacy of ruxolitinib, as was seen in COMFORT-II. 14 The rates of infections in JUMP were low and the infections were primarily grade 1/2; no new or unexpected infections were observed. Additionally, no cases of progressive multifocal leukoencephalopathy were reported.…”

The use of erythropoiesis‐stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib

“…Moreover, ruxolitinib has not been reported to improve the haemoglobin (Hb) level in patients already anaemic at treatment start (Harrison et al , ; Verstovsek et al , ). The use of erythropoiesis‐stimulating agents (ESAs) was discouraged in the COMFORT I study, however some responses to ESAs were seen in 13 patients from the COMFORT II study and reported in a post hoc analysis (McMullin et al , ).…”