SURVIVAL OUTCOMES in ACCELERATED and BLAST PHASE MPN: A REAL-WORLD ANALYSIS from the UK MPN CLINICAL STUDY GROUP.
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All Authors
Rampotas, A.
Kirkwood, A.
Brwon, C.
Alabdulkarim, A.
Ryan, J.
Wadelin, F.
Alimam, S.
Tun, P.
Lambert, J.
O'Sullivan, J.
LTHT Author
Khan, Alesia
LTHT Department
Oncology
Leeds Cancer Centre
Haematological Malignancy Diagnostic Service
Leeds Cancer Centre
Haematological Malignancy Diagnostic Service
Contributor Profession (Non Medical)
Publication Date
2025
Item Type
Conference Abstract
Language
Subject
Subject Headings
Abstract
Background Accelerated (AP) and blast phase (BP) MPN remain challenging entities with an inherently poor prognosis. Major obstacles remain the lack of unified therapeutic approaches, largely due to limited robust evidence regarding comparative efficacy of available therapies and a lack of prospective clinical trials. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only curative option but frequently limited by patient age, frailty, and comorbidities. We conducted a comprehensive, multicentre retrospective study evaluating survival in patients with AP/BP MPN across 15 hospitals in the UK, under the auspices of the UK MPN Clinical Study Group. Aims Highlight contemporary therapeutic approaches and real-world outcomes for a cohort of UK AP and BP MPN patients. Methods A retrospective analysis was conducted of 152 AP or BP MPN patients diagnosed across UK centres between 2014-2024. AP and BP cohorts were categorized based on treatment received or no active treatment in addition to whether they underwent allo-HCT. OS and PFS were analysed using Kaplan-Meier methodology and groups compared using Cox regression and the log-rank test. Results We identified 57 AP and 96 BP patients with a median of 71 years (range (r), 17-88). Driver mutation status was predominantly JAK2 mutated (63.6%) followed by CALR (20%). Median time from MPN diagnosis to development of AP or BP was 102 months (range, 0-273.6). Most of the cohort (92.9%) had received prior MPN-directed therapy (median 1 line, (r, 0-5)) before development of AP/BP. Overall response rate across therapies was 46.2%. Median OS for the entire cohort was 13.4 months (IQR: 3.0-31.0), with BP patients having significantly shorter OS than AP patients (median 6.44 vs. 21.9 months; p=0.039). Intensive chemotherapy (IC; n=30) associated with the longest OS (median 33.7 months), significantly better than azacytidine (AZA) monotherapy (n=19; 9.7 months, p=0.04) and venetoclax-based therapies (n=18; 14.9 months, p=0.003). Ruxolitinib (RUX) highlighted a favourable OS (25.3 months), though this was driven by combined therapy with HMA (N=17) in AP patients. Patients receiving no treatment had dismal outcomes (n=22; median OS: 2.2 months, p<0.001 compared to all cohorts). PFS followed similar patterns, with a median of 9.7 months (IQR: 3.0-27.2) for the entire cohort. IC demonstrated superior PFS (27.2 months) compared to AZA monotherapy (8.4 months, p=0.024) and venetoclax-based (9.1 months, p=0.003). RUX when combined with AZA tended to improved PFS compared to RUX alone, though only in AP disease (29.2 vs 18 months; p=0.046) (Figure 1). Allo-SCT was performed in 31 patients, with a higher utilisation in BP (24.2%) compared to AP (14.0%). As expected, patients elected for IC were more likely to receive allo-SCT (73.3% vs. 5.3% for azacytidine, p<0.001). Median OS post-SCT was 23.5 months, with no significant difference between AP and BP patients, although sample size limits definitive conclusions. Summary/Conclusion Markedly heterogenous therapeutic approaches were employed across UK centres. In this cohort, venetoclax-containing regimens did not show longer PFS. Although not suitable for many patients due to age/ fitness, IC was associated with the best OS and PFS outcomes, particularly in BP patients in whom allo-SCT remains the critical curative intervention. Clinical Trials are needed to optimize therapeutic stratification and sequencing for these patients.
Journal
HemaSphere