Early Ruxolitinib Initiation Increases Spleen Response Rates in Myelofibrosis

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Earlier ruxolitinib (Jakafi) initiation for myelofibrosis treatment was associated with significant increases in spleen response rates and spleen length improvement compared with later initiation, according to findings from a post hoc analysis of the single-arm, expanded-access, phase 3b JUMP trial (NCT01493414), which were published in Leukemia & Lymphoma.1

Among patients with myelofibrosis who initiated ruxolitinib within 12 months of diagnosis, the 12-week spleen response rate was 43.6% vs 34.9% among those who initiated ruxolitinib later than 12 weeks after diagnosis (P < .0001). Similar 12-week outcomes were observed between those who initiated ruxolitinib within 24 months (43.5%) and those who initiated ruxolitinib after 24 months (33.1%; P < .0001). Spleen response rates continued to be higher in those with earlier vs delayed ruxolitinib initiation at weeks 24 (≤ 12 months, 32.3% vs > 12 months, 28.3% [P < .01]; ≤ 24 months, 33.1% vs > 24 months, 26.6% [P < .001]) and 48 (≤ 12 months, 21.3% vs > 12 months, 17.6% [P < .05]; ≤ 24 months, 21.3% vs > 24 months, 16.8% [P < .01]).

Additionally, at week 12, among patients who initiated ruxolitinib within 12 months vs after 12 months, the mean spleen length change was –58.4% vs –49.0%, respectively (P < .0001); among those who initiated ruxolitinib within 24 months vs after 24 months, the mean spleen length change was –57.5% vs –47.5%, respectively (P < .0001). Mean spleen length changes continued to be greater in those with earlier vs delayed ruxolitinib initiation at weeks 24 (≤ 12 months, –60.1% vs > 12 months, –51.0% [P < .001]; ≤ 24 months, –59.2% vs > 24 months, –49.4% [P < .0001]) and 48 (≤ 12 months, –64.7% vs > 12 months, –51.3% [P < .0001]; ≤ 24 months, –63.1% vs > 24 months, –49.5% [P < .0001]).

“These results support early initiation of ruxolitinib to provide patients with the best opportunity to obtain a spleen response,” lead study author Pankit Vachhani, MD, and coauthors wrote in the paper.

Vachhani is an associate professor at the University of Alabama at Birmingham.

In 2011, the FDA approved ruxolitinib for the treatment of patients with intermediate- or high-risk myelofibrosis.2 This regulatory decision was backed by data from the phase 3 COMFORT-I (NCT00952289) and COMFORT-II trials (NCT00934544), in which patients with myelofibrosis who received ruxolitinib experienced significant spleen reductions and symptom improvements.

Continuing on this research trajectory, the JUMP trial investigated the efficacy and safety of ruxolitinib in patients with myelofibrosis in a setting similar to that of routine clinical practice.1 

JUMP enrolled 2233 patients with myelofibrosis across countries without access to ruxolitinib beyond the clinical trial setting, including those with low platelet counts (< 100 x 109/L) and those without splenomegaly.3 The primary analysis demonstrated that ruxolitinib generated meaningful reductions in spleen length and symptoms—including in patients with low platelet counts, as well as symptom improvements in those without splenomegaly. Moreover, a subset analysis showed that among patients with primary myelofibrosis and baseline data regarding bone marrow fibrosis severity (n = 1120), those who began ruxolitinib treatment within 2 years after their myelofibrosis diagnosis experienced increased spleen response rates compared with those who initiated treatment more than 2 years after diagnosis.4

Investigators conducted the present post hoc analysis of the entire JUMP population to verify the effects of ruxolitinib initiation timing on clinical outcomes. This analysis evaluated spleen response (defined as a ≥ 50% reduction in palpable spleen length from baseline); spleen length change from baseline, health-related quality of life (HRQOL; assessed by the percentage of patients achieving FACT-Lym response, defined as a ≥ 6.5–point increase from baseline in FACT-Lym score), and overall survival (OS; defined as time from first study dose to death).

Patients were stratified based on time between myelofibrosis diagnosis and ruxolitinib initiation (≤ 12 months vs > 12 months; ≤ 24 months vs > 24 months). Spleen and symptom responses were calculated in the full study population, including in patients with missing data.

Patient demographics and baseline characteristics were generally similar across subgroups. Notable differences included the mean time between initial myelofibrosis diagnosis and ruxolitinib initiation (≤ 12 months, 4.2 months, standard deviation [SD], 3.5; n = 818]; > 12 months, 79.3 months [SD, 66.9; n = 1415]; ≤ 24 months, 7.7 months [SD, 7.2; n = 1081]; > 24 months, 93.2 [SD, 66.8; n = 1152]). Across all subgroups, more than 90% of patients had a palpable spleen. The most common prior therapies among patients treated within 12 months vs those treated after 12 months were hydroxyurea (≤ 12 months, 41.9%; > 24 months, 67.8%), anagrelide (1.7%; 4.0%), and interferon (1.2%; 2.8%).

The mean ruxolitinib starting doses were similar between patients treated within 12 months and those treated after 12 months (≤ 12 months, 35.6 mg [SD, 7.7 mg]; > 12 months, 34.1 mg [SD, 8.6 mg]). Dose modifications were also similar between these 2 subgroups. The mean daily doses of ruxolitinib averaged over 4 weeks were highest over the first 4 weeks of treatment, at over 30 mg. From week 8 onward, these doses remained above 25 mg for all subgroups.

“Improvements in symptom response and OS remained consistent, regardless of the timing of ruxolitinib initiation,” the authors noted.

The FACT-Lym response rates at week 24 were similar across subgroups (≤ 12 months, 25.7%; > 12 months, 27.6%; ≤ 24 months, 28.1%; > 24 months, 25.8%). The mean percentage changes in FACT-Lym total score from baseline in these respective subgroups were 9.7% (SD, 20.1%), 10.9% (SD, 22.9%), 10.9% (SD, 22.9%), and 10.0% (SD, 20.9%).

Investigators did not observe significant OS differences between the subgroups, and the median OS was NR in any subgroup (≤ 12 months vs > 12 months, HR, 1.08 [95% CI, 0.83-1.4]; ≤ 24 months vs > 24 months, HR, 1.07 [95% CI, 0.83-1.4]).

“These results are consistent with analyses from other trials supporting clinical benefit of earlier ruxolitinib intervention in patients with myelofibrosis, most notably for superior spleen response,” the authors concluded.

References

1. Vachhani P, Guglielmelli P, Repp J, Hamer-Maansson JE, Braunstein E, Al-Ali HK. Early intervention with ruxolitinib improves spleen response in patients with myelofibrosis. Leuk Lymphoma. 2025;66(5):981-984. doi:10.1080/10428194.2024.2447884
2. FDA approves Incyte's Jakafi (ruxolitinib) for patients with myelofibrosis. News release. Incyte Corporation. November 16, 2011. Accessed April 25, 2025. https://investor.incyte.com/news-releases/news-release-details/fda-approves-incytes-jakafitm-ruxolitinib-patients-myelofibrosis#:~:text=WILMINGTON%2C%20Del.,90%20percent%20of%20MF%20patients.
3. Al-Ali HK, Griesshammer M, Foltz L, et al. Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Br J Haematol. 2020 Jun;189(5):888-903. doi:10.1111/bjh.16462
4. Palandri F, Al-Ali HK, Guglielmelli P, Zuurman MW, Sarkar R, Gupta V. Benefit of Early Ruxolitinib Initiation Regardless of Fibrosis Grade in Patients with Primary Myelofibrosis: A Post Hoc Analysis of the Single-Arm Phase 3b JUMP Study. Cancers (Basel). 2023;15(10):2859. doi:10.3390/cancers15102859