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A dysregulated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is characteristic of myelofibrosis (MF). Ruxolitinib, a potent JAK1/JAK2 inhibitor, was approved in 2011 for the treatment of primary and secondary intermediate-/high-risk MF. The approval was based on the results of the pivotal phase III COMFORT studies in patients with intermediate-2- or high-risk MF. In these studies, ruxolitinib demonstrated superiority over placebo and best available therapy with durable improvements in splenomegaly, MF symptoms, and quality of life (QoL), and was also associated with better overall survival.
Due to limited data on patients with intermediate-1-risk MF, the phase IIIb expanded-access JUMP study (NCT01493414) was initiated with the aim to collect safety and efficacy data for ruxolitinib in this population of patients. This study enrolled 2,233 patients, and initial results from patients treated with ruxolitinib for ≥ 1 year (n = 1,144), including those with intermediate-1-risk disease, showed reductions in spleen length and MF symptoms.1
A recent publication in Leukemia & Lymphoma by Vikas Gupta further evaluated clinical factors associated with response to ruxolitinib using data from the JUMP study.2 Here, we report key findings from this study.
The JUMP study is an open-label, multicenter, single-arm, phase IIIb expanded-access study in patients with MF. Eligibility criteria and study design are shown in Figure 1.
The starting doses of ruxolitinib were based on platelet count at baseline (Figure 1).
Spleen response was assessed using the International Working Group–Myeloproliferative Neoplasms Research and Treatment (IWG–MRT) criteria.
The primary endpoint was safety and tolerability of ruxolitinib.
Additional endpoints included:
Figure 1. Study design1,2
IPSS, International Prognostic Scoring System; MF, myelofibrosis.
Baseline characteristics of the 2,233 patients treated in the JUMP study from 2011 to 2017 and included in this analysis are shown in Table 1.
Table 1. Baseline characteristics of patients2
DIPSS, Dynamic International Prognostic Scoring System; Hb, hemoglobin; IPSS, International Prognostic Scoring System; MF, myelofibrosis; SD, standard deviation; WBC, white blood cell. |
|
Characteristic |
Patients (N = 2,233) |
---|---|
Median age (range), years |
67.0 (18–89) |
Mean time since initial diagnosis (SD), months |
51.7 (64.4) |
MF subtype, n (%) |
|
IPSS risk, n (%) |
|
DIPSS risk, n (%) |
|
Hb level, mean (SD), g/dL |
10.9 (2.3) |
Platelet count, mean (SD), × 109/L |
318.9 (238.6) |
Palpable spleen length, median (range), cm |
12.0 (0.5–45.0) |
Data on drug exposure are shown in Table 2.
Table 2. Ruxolitinib exposure2
Ruxolitinib exposure |
Patients |
n evaluable |
---|---|---|
Median duration of exposure, months (range) |
12.4 (< 0.1─59.7) |
2,233 |
Mean daily dose, mg |
28.7 |
2,233 |
Starting dose, % |
|
2,233 |
Ruxolitinib dose > 20 mg/day at Week 12, % |
|
|
Exposure to ruxolitinib, % |
|
2,101 |
Table 3. Factors associated with higher spleen response rates in multivariate analysis2
CI, confidence interval; IPSS, International Prognostic Scoring System; OR, odds ratio. |
|||
Factor predicting higher spleen response rates |
n/N |
% |
OR (95% CI) |
---|---|---|---|
IPSS |
|
|
|
Prior treatment |
|
|
|
Ruxolitinib dose at Week 12 |
|
|
|
This analysis revealed that lower IPSS risk, doses of ruxolitinib > 20 mg/day, and ruxolitinib given as first-line therapy are independent factors associated with higher spleen response rates.
No correlation between dose or demographic factors and patient-reported symptom improvement under ruxolitinib treatment was seen.
The limitations of the study include the lack of MF-specific health-related quality of life data and of cytogenetic and molecular data, and the limited length of follow-up time.
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