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

Abstract

JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis - a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib's mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov.

Figure 1.

Mean total daily dose^a,b of ruxolitinib. bid: twice daily; qd: once daily. ^aIncludes patients with complete drug administration dates (n=1141). ^b28 patients started at doses other than 5, 15, or 20 mg bid: 5 mg qd (n=1), 7.5 mg bid (n=1), 15 mg qd (n=6), 10 mg bid (n=16), 20 mg qd (n=4).

Figure 2.

Hemoglobin levels and platelet counts over time. (A) Hemoglobin levels over time. Boxes represent the upper to lower quartiles and the bars represent the range; the line is connected through the mean values. (B) Platelet counts over time. Boxes represent the upper to lower quartiles and the bars represent the range; the line is connected through the mean values.

Figure 3.

Spleen response. (A) Evaluable patients with a ≥25% decrease from baseline in palpable spleen length. (B) Best percent change from baseline in palpable spleen length at any time by week 48. Each bar represents data from an individual patient. Max: maximum; min: minimum. ^aNote: −100% change is defined as non-palpable. ^bOnly patients with spleen length assessments at baseline and at a post-baseline visit were included in this analysis.

Figure 4.

Quality of life responses. (A) Proportion of patients achieving a response in the FACT-Lymphoma total score. FACT: Functional Assessment of Cancer Therapy. ^aResponse was defined as the upper limit of the minimally important difference (FACT-Lym total score, 11.2 points). (B) Proportion of patients achieving a response on the FACIT-Fatigue Scale: FACIT: Functional Assessment of Chronic Illness Therapy. ^aResponse was defined as the upper limit of the minimally important difference (FACIT-Fatigue score, 3 points).