Safety and Efficacy of Ruxolitinib Retreatment after Treatment Interruption in Patients Enrolled in an Open-Label, Multicenter, Expanded-Access Study in Myelofibrosis

• Published in: Blood 2014-12, Vol.124 (21), p.5567-5567
• Main Authors: Gupta, Vikas, Tavares, Renato S, Griesshammer, Martin, Foltz, Lynda M, Raanani, Pia, Giraldo, Pilar, Al-Ali, Haifa Kathrin, Martino, Bruno, Tannir, Bayane, Ronco, Julian Perez, Ghosh, Jagannath, Vannucchi, Alessandro M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.5567.5567

BACKGROUND: Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated durable reductions in splenomegaly and myelofibrosis (MF)-related symptoms. Additionally, ruxolitinib proved superior to placebo and best available therapy in the phase 3 COMFORT studies and showed improved survival. In some patients (pts) receiving ruxolitinib, adverse events (AEs) may lead to treatment interruption; in such pts, AE management, dose optimization, and efficacy expectations may be balanced. This analysis provides further information about the efficacy and safety of ruxolitinib in pts who have restarted treatment after treatment interruption (cutoff date, 01 January 2014) in the JUMP (JAK Inhibitor Ruxolitinib in Myelofibrosis Patients) trial, a large, phase 3b, expanded-access program. METHODS: Pts with MF classified as high risk, intermediate-2 risk, or intermediate-1 risk, with a palpable spleen (≥ 5 cm from the costal margin), received starting doses of ruxolitinib based on their platelet counts at baseline (5 mg twice daily [bid; ≥ 50 to < 100 × 109/L], 15 mg bid [100 to 200 × 109/L], or 20 mg bid [> 200 × 109/L]). Endpoints included safety and tolerability, as well as changes in spleen length, symptoms, and laboratory values. This analysis included all pts who started study treatment ≥ 1 year before data cutoff and had ≥ 1 dose interruption of ≥ 7 days. RESULTS: This analysis included 207 pts (primary MF, 68.1%; female, 53.1%; median age, 69 years) presenting with baseline medians: spleen length, 13 cm (range, 1.0-35.0 cm); hemoglobin, 99 g/L (50.7% of pts with < 100 g/L); and platelets, 199.5 × 109/L. At data cutoff, most pts (60.9%) remained on treatment (38.2%) or completed treatment per protocol (22.7%); the main reasons for discontinuation included AEs (18.4%), death (6.8%), disease progression (5.3%), and other (8.7%). Overall, the median duration of exposure was 12.5 months: 1.9 months from baseline to interruption and 6.5 months after restart. The mean daily dose was 30.5 mg prior to treatment interruption and 19.4 mg after treatment restart. Dose interruptions lasted 7 to 14 days in 41.1% of pts (15 to 21 days, 26.6%; > 21 days, 32.4%) and were mostly due to AEs (92.3%). Most pts (67.1%) had only 1 dose interruption. At weeks 12, 24, and 48, overall 45%, 53%, and 54% of pts, respectively, achieved a ≥ 50% reduction from baseline in palpable spleen length. In addition, at the same time points, 29%, 23%, and 23% achieved reductions from 25% to 50%. 68.