Ayala, RosaFernández, Rafael AlonsoGarcía-Gutiérrez, ValentínAlvarez-Larrán, AlbertoOsorio, SantiagoSánchez-Pina, Jose MCarreño-Tarragona, GonzaloÁlvarez, NoemiGómez-Casares, María TeresaDuran, AntoniaGorrochategi, JulianHernández-Boluda, Juan CarlosMartinez-Lopez, Joaquin2024-09-162024-09-162023-04-16EJHaem . 2023;4(2):401-409.https://hdl.handle.net/20.500.12105/23116This phase Ib, non-randomized, open-label study evaluates the safety and tolerability of ruxolitinib in combination with nilotinib and prednisone in patients with naïve or ruxolitinib-resistant myelofibrosis (MF). A total of 15 patients with primary or secondary MF received the study treatment; 13 patients had received prior ruxolitinib treatment (86.7%). Eight patients completed seven cycles (53.3%) and six patients completed twelve cycles of treatment (40%). All the patients experienced at least one adverse event (AE) during the study (the most common AEs were hyperglycemia, asthenia, and thrombocytopenia), and 14 patients registered at least one treatment-related AE (the most common treatment-related AEs were hyperglycemia (22.2%; three grade 3 cases). Five treatment-related serious AEs (SAEs) were reported in two patients (13.3%). No deaths were registered throughout the study. No dose-limiting toxicity was observed. Four out of fifteen (27%) patients experienced a 100% spleen size reduction at Cycle 7, and two additional patients achieved a >50% spleen size reduction, representing an overall response rate of 40% at Cycle 7. In conclusion, the tolerability of this combination was acceptable, and hyperglycemia was the most frequent treatment-related AE. Ruxolitinib in combination with nilotinib and prednisone showed relevant clinical activity in patients with MF. This trial was registered with EudraCT Number 2016-005214-21.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacional372062584240110.1002/jha2.6852688-6146EJHaemopen access