RUXOLITINIB IMPROVED SURVIVAL in MYELOFIBROSIS PATIENTS with 1 or MORE HIGH MOLECULAR RISK MUTATIONS.
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All Authors
Teh, C.
Jain, M.
Cargo, C.
Atiyah, N.
Bagguley, T.
Smith, A.
LTHT Author
Teh, Chun
Jain, Manish
Jain, Manish
LTHT Department
Leeds Cancer Centre
Haematology
Oncology
Haematology
Oncology
Non Medic
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS , AGED , DRUG THERAPY , WOMEN , CLINICAL PROTOCOLS , FOLLOW-UP-STUDIES , HAEMATOLOGIC DISEASES , LEUKOCYTES , MEN , SURVIVAL RATE , METAPLASIA , ANTINEOPLASTIC AGENTS
Subject Headings
Abstract
Background: Ruxolitinib is licensed for the treatment of splenomegaly and constitutional symptoms related to myelofibrosis. It has been available to our study populations since 2012. The survival benefit of ruxolitinib in patients with IPSS Intermediate-2 and high-risk scores has been subjected to considerable debate. Moreover, it is uncertain if ruxolitinib would mitigate the adverse outcomes of patients with high molecular risk mutations including ASXL1, EZH2, IDH1/2, SRSF2 and U2AF1. Aim(s): To establish if ruxolitinib conferred survival benefit in the real-world setting. Additionally, we assessed if ruxolitinib improved the survival of patients with one or more high molecular risk mutations. Method(s): We identified cases of primary myelofibrosis, post-PV and post-ET myelofibrosis diagnosed between 2012 and 2019, within the UK's Haematological Malignancy Research Network (HMRN) covering approximately 4 million populations, and followed up to 2023. Data on demographics, treatment and high throughput sequencing were collected. Mortality data was obtained from the Office for National Statistics. We compared the characteristics and outcomes of patients who received ruxolitinib as 1st line treatment with patients who did not receive ruxolitinib as 1st line treatment. Result(s): 129 Patients were diagnosed with myelofibrosis over an 8-year period. 74 Patients (57.4%) have been treated with ruxolitinib as 1st line therapy whereas 55 patients (42.6%) did not get ruxolitinib as 1st line therapy. There were more male patients (68.9% vs 47.3%, p=0.013) and higher proportion of patients with at least 1 high molecular risk mutation (63% vs 15%, p=0.001) in the ruxolitinib 1st line treatment group compared to non-ruxolitinib 1st line group. Other baseline characteristics including median age (72.6 vs 71.0, p=0.41), median Hb (10.8 g/dL vs 10.2 g/dL, p=0.44), median white cell count (9.4 x109/L vs 10.3 x109/L, p=0.78) and transfusion dependency (27% vs 25.5%, p=0.84) were similar between the two groups. In patients who received ruxolitinib 1st line, the median duration of treatment was 2.0 years (95% CI 1.2-3.7). The median follow-up was 9.3 years (95% CI 5.9-9.6) in patients who received ruxolitinib 1st line, 7.8 years (95% CI 5.4-8.7) in nonruxolitinib group. Median survival was 5.3 years (95% CI 4.0-6.3) in ruxolitinib 1st line patients, 4.5 years in nonruxolitinib 1st line patients (log-rank p-value 0.11) Molecular data was available in 73 patients. 39 Patients (53.4%) have no high molecular risk mutation, 25 patients (34.2%) have 1 mutation and 9 (12.3%) patients with more than 1 mutations. The corresponding median OS were 5.3 years (95% CI 3.4-NR), 3.4 (95% CI 1.1-NR), 2.8 (95% CI 1.5-NR). 17 (50%) Patients with at least 1 high molecular risk mutation received ruxolitinib as first line therapy whereas 16 (48.5%) did not receive ruxolitinib as 1st line therapy. In patients with at least 1 high molecular risk mutation, median survival of patients who had ruxolitinib as first line therapy was 5.2 years (95% CI 1.5-NR), significantly longer than non-ruxolitinib as 1st line therapy with 1.8 years (95% CI 0.3-3.4), log-rank pvalue 0.034. Summary/Conclusion: In this real-world setting, the median survival of myelofibrosis patients who received ruxolitinib as 1st line therapy was no better than patients who did not receive ruxolitinib as 1st line therapy. The median survival of patients with at least 1 high molecular risk mutation, however, was significantly longer in patients who have ruxolitinib as 1st line therapy. (Figure present).
Journal
HemaSphere