Real-world analysis of ruxolitinib in myelofibrosis: interim results focusing on patients who were naïve to JAK inhibitor therapy treated within the JAKoMo non-interventional, phase IV trial

Abstract

Ruxolitinib (RUX) is a Janus kinase 1/2 inhibitor (JAKi) approved in the EU for treating disease‑related splenomegaly or symptoms in adults patients with myelofibrosis (MF). This is an interim analysis of JAKoMo, a prospective, non‑interventional, phase IV study in MF. Between 2012-2019 (cutoff March 2021), 928 patients (JAKi-naïve and -pretreated) enrolled from 122 German centers. This analysis focuses on JAKi-naïve patients. RUX was administered according to the Summary of Product Characteristics. Compared to the COMFORT-I, -II, and JUMP trials, patients in JAKoMo were older (median 73 years), had poorer Eastern Cooperative Oncology Group (ECOG) performance statuses (16.5% had ECOG ≥ 2), and were more transfusion dependent (48.5%). JAKoMo represents the more challenging patients with MF encountered outside of interventional studies. However, patients with low-risk International Prognostic Scoring System (IPSS) scores or without palpable splenomegaly were also included. Following RUX treatment, 82.5% of patients experienced rapid (≤ 1 month), significant decreases in palpable spleen size, which remained durable for 24 months (60% patients). Symptom assessment scores improved significantly in Month 1 (median -5.2) up to Month 12 (-6.2). Common adverse events (AEs) were anemia (31.2%) and thrombocytopenia (28.6%). At cutoff, 54.3% of patients had terminated the study due to, death, AEs, or deterioration of health. No new safety signals were observed. Interim analysis of the JAKoMo study confirms RUX safety and efficacy in a representative cohort of real-world, elderly, JAKi-naïve patients with MF. Risk scores were used in less than half of the patients to initiate RUX treatment.Trial registration: NCT05044026; September 14, 2021.

Keywords: JAK1/2 inhibitors; JAKoMo clinical trial; Myelofibrosis; Patient-reported outcome measures (PROMs); Real-world evidence; Ruxolitinib.

Fig. 1

MPN-SAF questionnaire results at baseline. Mean with SEM (n = 464). Symptom severity was rated on a scale from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). MPN-SAF TSS has a possible range of 0–100, with 100 representing the highest level of symptom severity. Abbreviations: BFI Brief Fatigue Inventory, SEM standard error of the mean, MPN-SAF Myeloproliferative Neoplasm Symptom Assessment Form, TSS total symptom score

Fig. 2

Spleen length below costal margin by palpation during the course of the trial. Median with lower and upper quadrants (n = 464)

Fig. 3

Differences in spleen length measurement from baseline to last post-baseline visit by ultrasound. Abbreviations: RUX ruxolitinib. Mean duration from baseline to the last assessment of spleen size by ultrasound was 18 months. Median time to last spleen measurement by ultrasound was 16.6 months

Fig. 4

Pearson correlation between spleen size measured by palpation vs in ultrasound (n = 233). Identical values have been deleted. Spleen size by palpation is analyzed as values below costal margin

Fig. 5

MPN-SAF TSS changes over time in comparison to baseline. MPN-SAF TSS difference is shown in comparison to baseline for total patient cohort and divided by subentity n = 464). Abbreviations: MPN-SAF Myeloproliferative Neoplasm Symptom Assessment Form, TSS total symptom score, PMF primary myelofibrosis, PPV-MF post-polycythemia vera myelofibrosis, PET-MF post-essential thrombocythemia myelofibrosis

Fig. 6

Overall survival analysis in JAKoMo patients (Kaplan–Meier estimator). (A) Survival analysis for all patients; (B) Survival analysis for patients according to their IPSS risk score at baseline. p = 0.268 by Log-rank (Mantel–Cox) test (C) Survival analysis for patients according to their myelofibrosis subtype