Ruxolitinib Is Linked With High Spleen Responses in IPSS Low-Risk Myelofibrosis

November 25, 2020 — Ruxolitinib, when administered earlier on in the treatment course, led to high spleen response rates in patients with low-risk International Prognostic Scoring System myelofibrosis.

Ruxolitinib (Jakafi), when administered earlier on in the treatment course, led to high spleen response rates in patients with low-risk International Prognostic Scoring System (IPSS) myelofibrosis, according to an analysis of the phase 3b JUMP study (JAK Inhibitor RUxolitinib in Myelofibrosis Patients; NCT01493414).1 However, higher doses of ruxolitinib did not demonstrate symptom improvement.

The univariate analysis indicated that certain baseline factors such as IPSS low– and intermediate-1–risk status, hemoglobin levels of at least 10 g/dL, a platelet count of at least 100 x 109, time since myelofibrosis diagnosis of up to 2 years, blasts of less than 1%, receiving ruxolitinib up front, and a ruxolitinib dose of more than 20 mg/day were all associated with higher spleen response rates. 

Additionally, the predictive benefit of receiving a prior treatment compared with no prior therapy was restricted to patients with dynamic IPSS (DIPSS) intermediate-2– or high-risk disease (37.3% vs 26.8%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.45-0.84). 

In the multivariate analysis, there were also several predictors of significant response including IPSS low– or intermediate-1– risk, frontline ruxolitinib, and a ruxolitinib dose of at least 20 mg at week 12. 

Here, frontline ruxolitinib was also determined to be a significant predictor of spleen response, regardless of DIPSS risk status(low– /intermediate-1– risk, 45.2% vs 38.0%; aOR, 0.59; 95% CI 0.37-0.93; intermediate-2– /high-risk: 37.3% vs 26.8%; aOR, 0.46; 95% CI 0.27-0.79).

Higher doses of ruxolitinib were found to correlate with higher spleen response rates in both the univariate and multivariate analyses. Patients who received over 20 mg per day of ruxolitinib were found to have higher responses compared with those who were given 20 mg or less (41.3% vs 30.4%; aOR, 0.47; 95% CI, 0.33-0.68).

“The predictive factors identified in this study are applicable to routine clinical practice and might help healthcare professionals optimize the use of ruxolitinib in the management of patients with myelofibrosis,” lead study author Vikas Gupta, MD, of Princess Margaret Cancer Centre, in Toronto, Canada, and investigators wrote.

Although allogeneic stem cell transplant is a viable option for some patients, the majority of them are not candidates due to the following factors: advanced age, associated comorbidities, and lack of suitable donors. Therefore, standard approaches for patients with myelofibrosis are mostly palliative, with an emphasis on symptom control. 

As approximately 90% of patients with myelofibrosis have JAK2, CALR, or MPL mutations present, investigators tested JAK1/2 inhibitor ruxolitinib in this patient population, as it has demonstrated durable improvements in splenomegaly, symptoms, and health-related quality of life when compared with placebo.2,3

In December 2014, the FDA approved ruxolitinib as a treatment for patients with PV who are resistant or intolerant to hydroxyurea.

The international, single-arm, open label, phase 3b, expanded-access JUMP study, enrolled patients with primary or secondary myelofibrosis, according to World Health Organization criteria.4 To be eligible for enrollment, patients were aged 18 years or older and have a baseline platelet count of 50 x 109/L. 

The starting dose of ruxolitinib was based on baseline platelet counts: 50 to 100 × 109/L (5mg of ruxolitinib twice daily), 100 to 200 × 109/L (15 mg twice daily), and greater than 200 × 109/L (20 mg twice daily). The study allowed for dose increases in the case of insufficient efficacy, provided that neutrophil and platelet counts were acceptable. Dose decreases and interruptions were mandatory, in some cases, for safety reasons.

The primary end point was to determine the safety and tolerability of ruxolitinib; secondary end points consisted of the proportion of patients with a 50% or greater reduction in palpable spleen length, and change from baseline in patient-reported outcome measures assessing fatigue and symptoms.

In the analysis of predictive factors of spleen responses, 2233 patients who were treated from 2011 to 2017 at 279 clinical sites throughout 26 countries in Europe (82%; n = 1831), Latin America (8.5%; n = 190), North America (2.4%; n = 53), and other regions (7.1%; n = 159) were included. 

The median age was 67 years, and the mean time from initial diagnosis was 51.7 months. Nearly half of all patients had IPSS risk status information missing (49.1%), though 0.1% were defined as low-risk, 16.3% were considered low/intermediate-1–risk, and 34.6% were found to be intermediate-2–/high-risk.

The analysis also examined factors that were associated with symptom improvement. In the univariate analysis, results showed that a titrated total daily ruxolitinib dose of more than 20 mg/day at week 12 was linked with higher symptom response vs those who received 20 mg or less, according to functional assessment of cancer therapy–lymphoma score (48.2% vs 56.7%; OR, 0.71; 95% CI, 0.57-0.88) and functional assessment of chronic illness therapy-fatigue scale (44.9% vs 51.5%; OR, 0.77; 95% CI, 0.62-0.96). 

Conversely, the multivariate analysis did not find any associations between baseline characteristics or titrated dose at week 12 and symptom response.

The majority of patients enrolled on JUMP experienced a reduction in spleen size while receiving ruxolitinib, with 2049-assessed patients experiencing a mean change of –68.3% from baseline in palpable spleen length (median, –75.0%; 95% CI, 100.0%-133.3%). At week 24, investigators reported that of the evaluable patients, 34.3% (n = 672/1960) had achieved a spleen response by International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria. 

Overall survival (OS) was not reached in patients with DIPSS-low– or intermediate-1–risk disease. Patients with DIPSS intermediate-2–/high-risk disease who had achieved a spleen response at week 24 had a median OS of 229.1 weeks compared with 253.6 weeks in those who did not respond. However, investigators cautioned that small sample sizes were utilized in this study, with 32 patients achieving a spleen response vs 122 who did not.


  1. Gupta V, Griesshammer M, Martino B, et al. Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study. Leuk & Lymph. 2020. doi:10.1080/10428194.2020.1845334
  2. Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. AM J Hematol. 2016;91(12):1262-1271. doi:10.1002/ajh.24592
  3. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl Med. 2012;366(9):799-807. doi:10.1056/NEJMoa1110557
  4. Al-Ali HK, Griesshammer M, le Coutre P, et al. 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. Haematologica. 2016;101(9):1065-1073. doi:10.3324/haematol.2016.143677