Discussion
liver dysfunction, thrombocytopenia, PET-MF, anemia, SAEs, PPV-MF, PMF
DISEASE PROGRESSION, DISEASE, THROMBOCYTOPENIA, ANEMIA, ONCOLOGY
Here, we report on the largest German cohort of patients with MF treated according to the approved label with RUX almost exclusively by hematologists/oncologists in the outpatient office setting and, thus, reflective of the true, real-world scenario of RUX treatment as per the SmPC. This interim analysis focusses on 464 patients with PMF, PPV-MF, or PET-MF not previously treated with RUX or any other JAKi (Arm A).There were no further restrictions regarding comorbidities, dynamic (D)IPSS risk, or spleen size. Patients with low-risk disease were included independent of their blood counts. Despite the liberal inclusion criteria, median spleen length at baseline (14 cm BCM) was comparable to the JUMP (13.3 cm) and COMFORT-II (14 cm) trials [One rather surprising finding was the high percentage (58%) of missing data for IPSS (or DIPSS) scoring, suggesting that physicians involved in this trial did not employ (D)IPSS scoring when deciding to commence RUX treatment. This contrasts current guidelines by the German Society of Hematology and Medical Oncology [Interestingly, the JAKoMo study cohort showed signs of both earlier disease (few dry taps, lower IPSS scores) and, concomitantly, more advanced disease, with around half of the patients in the JAKoMo trial (48.5%) having been transfusion dependent at baseline, almost twice as much as in the JUMP trial (25.9%) [Median treatment duration in patients participating in the JAKoMo trial was 1.5 years, a little longer than in the JUMP trial. Primary reasons for RUX discontinuation were also similar in both trials, particularly thrombocytopenia and disease progression. Importantly, kidney and liver dysfunction were almost never stated as reasons for dose adjustments in our trial, suggesting that this was not deemed a significant clinical problem.Median spleen length was markedly and rapidly reduced from 13.9 cm BCM at baseline to 8.0 cm after 2 months of therapy (reduction of 42%); this was comparable to efficacy reported in the JUMP trial (40%) and slightly lower than that reported in the COMFORT-II (56%) trial. Comparison of spleen length by palpation and by ultrasound suggested that spleen length by palpation may be overestimated; however, despite the overall overestimation by palpation, intraindividual correlation between both measures in our patients was very accurate, leading us to conclude that overestimation by palpation does not vary between several visits. As spleen sizes via palpation correlated well with ultrasound length measurements, this suggests that palpation is a cost-effective and simple alternative in the routine setting, but it might overestimate actual spleen size.Since the beginning of RUX clinical development, clinical trials in MF have included spleen size and symptom reductions as clinical endpoints. Although these endpoints translate into benefits for patients by providing better quality of life, a landmark trial [In the real-world setting of our study, RUX was fairly well tolerated, revealing no new safety signals. As described, the most frequent AEs included anemia in 31% and thrombocytopenia in 27% of patients. Anemia-related SAEs occurred in 13% of patients in this population (in comparison to 4.5% of anemia SAEs in the JUMP trial [In addition to the points addressed above, limitations to this analysis include the observatory character of the trial with limited on-site monitoring of the data, and this may also explain the missing values, particularly regarding IPSS scoring and molecular genetics assessments.