Prospective Follow-up of Patients with Myelofibrosis (MF) and Treated with Ruxolitinib in France: The Rumycup Study

Introduction MF is a clonal blood disease affecting 1.5 per 100,000 people worldwide. MF is characterized by megakaryocytic proliferation and atypia, usually accompanied by reticulin and/or collagen fibrosis, splenomegaly, anemia, and constitutional symptoms. Current treatments for MF are palliative, aiming to alleviate symptoms and restore quality of life.

Ruxolitinib (Jakavi®) is an oral JAK1/JAK2 inhibitor, first in its class, and currently approved in >90 countries for the treatment of splenomegaly or disease-related symptoms in patients with MF. This study aimed to evaluate the use and outcome of ruxolitinib therapy during the first year after initiation in clinical practice.

Methods RUMYCUP was a French, multicenter, non-interventional, prospective study. Adult patients with MF primary or secondary to polycythemia vera (PV) or essential thrombocythemia (ET) and for whom a decision was taken to initiate treatment with ruxolitinib, were included in the study. Primary data were collected at inclusion and at 3, 6, 9 and 12 months.

The primary objective of this study was to assess ruxolitinib exposure during 11.5 months after treatment initiation. The secondary objectives were to describe patients' characteristics and treatment with ruxolitinib.

Results Between Oct-2018 and Sep-2021, 152 patients were enrolled in the study in 49 French centers. Of them, 146 were included in the analysis population and 150 were included in the safety population.

Overall, 50.7% of patients (95% CI: 42.3; 59.0) received ruxolitinib for at least 11.5 months, with a higher proportion in patients with splenomegaly at initiation than in those with no or unknown splenomegaly (53.8% vs 37.9%).

At inclusion, 58.9% of patients were male, and the mean age was 70.9 years. Half of the patients were diagnosed with primary MF, 33.6% had a post-ET and 15.8% had a post-PV MF. The driver mutations were JAK2V617F in 69.2% of patients, CALR in 11.6%, and MPL in 4.8%. Among patients with available prognostic scores, 30.9% had a high-risk disease, 36.8% and 26.5% had an intermediate 2 or 1 risk disease, respectively, and 5.9% had a low risk disease, based on the International Prognosis Scoring System.

At inclusion, 27.4% of patients had hepatomegaly, 32.9% had night sweats, 21.2% had weight loss, and 5.5% had fever. Within the 3 months prior to ruxolitinib initiation, 72.3% of patients did not receive any transfusion of Red Blood Cell (RBC) concentrates, 17.0% had >2 and 10.6% had 1 or 2 RBC transfusions. The median length of the spleen measured by palpation was 8.0 cm below costal margin and the median decrease was of 2.5 cm at Month 12.

At inclusion, 58.2% of patients had had at least one previous treatment line and 19.9% two or more lines. As first line, 55.8% of patients received hydroxyurea. During follow-up, <43% of patients received RBC units and <10% of patients received platelet transfusions.

Ruxolitinib was initiated at a median dose of 25 mg/day, and the main reasons for starting treatment were splenomegaly (78.1% of patients) and symptoms (58.9%). During follow-up, the dose was increased in 26.7% of patients (mostly for optimization of efficacy), decreased in 14.4% (mostly due to the occurrence of an adverse event [AE], including lack of efficacy) and both increased and decreased in 21.2% of patients. The treatment was temporarily stopped for 20% of patients, for a median 0.5 months. For 27.6% of them, the treatment interruption lasted >21 days.

A total of 513 AEs were described in 89.3% of patients. AEs suspected to be related to ruxolitinib were reported in 57.3% of patients, and 58.0% reported 251 serious AEs (SAEs). Overall, 42 SAEs reported in 24 (16.0%) patients led to death. One SAE suspected to be related to ruxolitinib treatment (hemorrhage), led to the death of one patient. The 23 other deaths were not suspected to be related to ruxolitinib treatment and the most frequent SAEs leading to death, were disease progression (5/150 patients) or myelofibrosis and malignant neoplasm progression (3/150), COVID-19 (3/150) and other infections (5/150).

Conclusion This 1-year follow-up conducted in France gives a first overview on the exposure to treatment and disease characteristics in patients with MF treated with ruxolitinib in clinical practice. The evaluation in real life conditions showed that half of the patients included in this study maintained ruxolitinib treatment for at least 11.5 months after initiation.

Kiladjian:AbbVie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boyer perrard:Novartis: Honoraria. Laribi:AbbVie, AstraZeneca, Beigene, Iqone, Janssen, Novartis, Takeda: Honoraria. Ianotto:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ranta:Janssen: Membership on an entity's Board of Directors or advisory committees. Cony-Makhoul:Pfizer, Novartis Pharma, Incyte: Consultancy, Other: Support for travels; Research grants to CH Annecy Genevois for observational and clinical studies, Speakers Bureau. Slimani:Novartis: Current Employment. Etienne:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte Biosciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.