Ruxolitinib Demonstrates Safety, Efficacy in Myelofibrosis, Expanded Access Trial Confirms

Worldwide clinical experience with the JAK1/2 inhibitor ruxolitinib in patients with myelofibrosis has yielded safety and efficacy data similar to results of a pivotal randomized trial.

Lynda Foltz, MD

Worldwide clinical experience with the JAK1/2 inhibitor ruxolitinib (Jakafi) in patients with myelofibrosis has yielded safety and efficacy data similar to results of a pivotal randomized trial, a review of data from an expanded access program showed.1

Data for the analysis came from JAK Inhibitor Ruxolitinib in Myelofibrosis Patients (JUMP), an expanded access phase IIIb trial. The principal objectives were safety and efficacy of ruxolitinib in patients with myelofibrosis and no access to ruxolitinib outside of a clinical trial. Other endpoints included the proportion of patients with >50% reduction in spleen length, patient-reported outcomes, progression-free survival (PFS), leukemia-free survival (LFS), and overall survival (OS).

Overall, the patients had an estimated 48-week OS of 94% (95% CI, .93-.95), LFS of 92% (95% CI, .91-.93), and PFS of 90%.

More than 60% of patients remained on treatment or completed per-protocol and transitioned to treatment with the commercially available drug. A majority of patients had greater than 50% reduction in palpable spleen length, and another 25% of patients had 20% to 50% reductions in spleen length.

Overall, most adverse events (AEs) were grade 1/2. Anemia was the most common AE, reaching grade 3/4 severity in one-third of patients, as reported during the 2016 ASH Annual Meeting.

“Ruxolitinib was well tolerated and had an adverse event profile consistent with what has been previously reported,” Lynda Foltz, MD, head of Hematology at the University of British Columbia, and co-investigators concluded in a poster presentation.

“The most common adverse events were anemia and thrombocytopenia, but they rarely led to discontinuation. The majority of patients who received erythropoiesis-stimulating agents with ruxolitinib had resolution or improvement of their anemia. Most patients experienced reductions in splenomegaly and symptoms with ruxolitinib treatment.”

The analysis comprised 2233 patients treated in 26 countries. The study population came primarily from Europe (82%), followed by South America (8.5%), Canada and Mexico (2.4%), and other regions (7.1%). Patients started treatment with a ruxolitinib dose of 5, 15, or 20 mg BID, depending on baseline platelet count.

Foltz and colleagues reported that 39.1% of patients discontinued treatment for reasons that included AEs (17.7%), investigator-determined disease progression (8.6%), death (4.1%), withdrawal of consent (3.4%), and physician decision (3.9%). Hematologic AEs most often leading to discontinuation were thrombocytopenia (3.9%), anemia (2.2%), leukocytosis (0.8%), and neutropenia (0.3%). Among nonhematologic AEs leading to discontinuation, infection was the most common reason (2.8%); all others had discontinuation rates <1%.

Overall, anemia occurred in 58.7% of patients and was grade 3/4 severity in 34.1%. Thrombocytopenia occurred in 43.8% of patients (16.3% grade 3/4) and neutropenia in 6.5% of patients (4.5% grade 3/4). The median baseline platelet level (254 x 109/L) declined during the first 4 weeks of treatment with ruxolitinib and remained stable thereafter.

Nonhematologic AEs were led by pyrexia (15.6%, 2.3% grade 3/4), asthenia (14.9%, 2.2%), diarrhea (12.0%, 1.1%), and fatigue (9.7%, 1.0%). The most common grade 3/4 nonhematologic AE was pneumonia (4.3%).

Serious adverse events included anemia (4.0%), thrombocytopenia (1.1%), pneumonia (5.1%), pyrexia (3.4%), and cardiac failure, dyspnea, abdominal pain, sepsis, respiratory failure, and urinary tract infection (all <2%).

The data showed that 56.6% of patients attained >50% reduction in spleen length after 24 weeks of treatment, increasing to 61.6% at 48 weeks. Additionally, the proportion of patients with 20% to 50% reductions in spleen length was 23.3% at 24 weeks and 18.9% at 48 weeks. During follow-up to 72 weeks, 70.2% of patients had >50% reduction in spleen length at some point.

Loss of response (defined as return to baseline spleen value after >50% reduction) occurred in 12.8% of patients. The Kaplan-Meier estimated probability of maintaining >50% reduction from baseline for 48 and 60 weeks was 87% and 80%. The mean best percentage reduction from baseline was 66.5% and the median was 70.0%

Clinically meaningful symptom improvement occurred as early as 4 weeks and was maintained over time. The investigators found that 43% of patients achieved symptomatic improvement (minimally important difference from baseline) at each assessment with the FACT-Lym TS questionnaire. Additionally, 45% to 50% met response criteria at each assessment with the FACIT-Fatigue scale.


Foltz L, Paulmbo GA, Martino B, et al. Safety and efficacu of ruxolitinib for the final enrollment of JUMP: an open-label, multicenter, single-arm expanded-access study in patients with myelofibrosis. Presented at: 58th ASH Annual Meeting and Exposition; December 2-6, 2016; San Diego, CA. Abstract 3107.