Contributions
Abstract: PB2286
Type: Publication Only
Background
Ruxolitinib (RUX), the oral Janus kinase (JAK)1/2 inhibitor, is approved for treating disease-related splenomegaly or symptoms in adults with primary myelofibrosis (PMF), post-essential thrombocythaemia (PET)-MF, or post-polycythaemia vera (PPV)-MF. In March 2016, RUX was commissioned in Northern Ireland (NI) for higher-risk MF patients (IPSS 2+) and had only been available through clinical trials or special funding requests before then.
Aims
To assess the clinical outcomes of MF patients treated in NI and to compare the efficacy and safety of RUX with best alternative therapy (BAT) in the 'real-world' setting.
Methods
We performed a multicentre retrospective analysis of MF patients referred to a large tertiary cancer centre, from 1996 to 2017. Clinical data were obtained from electronic care records, laboratory and pharmacy databases. Survival analysis was estimated using the Kaplan-Meier method and standard log-rank test.
Results
We identified 47 patients, 46 of which were included in the whole cohort analysis (1 was excluded due to insufficient data). The median age at diagnosis was 65 years (35–83) and 63% were male. There were 24 (52%) PMF, 9 (20%) PET-MF, 11 (24%) PPV- MF, 2 (4%) post-myeloproliferative neoplasm-unclassified (PMPN)-MF patients, comprising 35% high-risk, 28% intermediate-2 (int- 2), 35% intermediate-1 (int-1) and 2% low risk patients. A driver mutation was detected in 89% (78% JAK 2+; 11% CALR+). The whole cohort median survival was 8.5 years (0.5–21.5). Of the 46 patients, 28 (61%) received RUX. Five were excluded from further analysis (2 had received another JAK inhibitor; 3 had stem cell transplantation). Of the remaining 41, 24 (59%) received RUX; 10 (24%) as first-line therapy. Baseline demographics were similar between patients treated with RUX or BAT. The RUX group comprised 29% high-, 38% int-2 and 33% int-1 risk patients, and had a significant 5-year overall survival (OS) advantage from time of diagnosis vs BAT; 77% (95% CI 53–90) vs. 57% (95% CI 27–79); p=0.044. Median survival in the BAT group was 6.3 years for int-1, 1.4 years for int-2, and 2.1 years for high-risk patients. Median survival in the RUX group was 1.8 years for high-risk and was not reached for int-1 and int-2 risk patients. There was no survival difference between int-1 and int-2 risk RUX patients; however, int-1 risk RUX patients had a notable survival advantage vs int-1 risk BAT patients; 5y OS 100% vs 86% (95% CI 33–98); p=0.045. In the RUX group, 1y OS was 82% (58–93) with median follow-up of 14 months (1– 50). The estimated discontinuation rate was 31% (95% CI 16–55) at 1 year. At the time of analysis, 10 patients had stopped RUX; 5 died, 4 progressed/no response, and 1 due to adverse effects (AE). Two (8%) transformed to acute myeloid leukaemia. The most common grade 3/4 AEs were thrombocytopaenia (25%) and anaemia (54%), with 33% requiring dose reduction or interruption. The most common non-haematological AEs were infection (42%). Data collection of spleen response and symptom control is underway but incomplete.
Conclusion
In summary, our whole cohort data demonstrate similar outcomes for MF patients treated in NI compared with contemporary clinical trials. Notably, there was a significant survival advantage for patients treated with RUX vs BAT in all risk groups, including intermediate-1 risk patients who at present do not meet funding criteria to receive RUX. This data must be interpreted with caution due to the limited follow-up but it suggests a potentially unmet clinical need in lower-risk MF patients that requires further study.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Clinical data, Janus Kinase inhibitor, Myelofibrosis, Ruxolitinib
Abstract: PB2286
Type: Publication Only
Background
Ruxolitinib (RUX), the oral Janus kinase (JAK)1/2 inhibitor, is approved for treating disease-related splenomegaly or symptoms in adults with primary myelofibrosis (PMF), post-essential thrombocythaemia (PET)-MF, or post-polycythaemia vera (PPV)-MF. In March 2016, RUX was commissioned in Northern Ireland (NI) for higher-risk MF patients (IPSS 2+) and had only been available through clinical trials or special funding requests before then.
Aims
To assess the clinical outcomes of MF patients treated in NI and to compare the efficacy and safety of RUX with best alternative therapy (BAT) in the 'real-world' setting.
Methods
We performed a multicentre retrospective analysis of MF patients referred to a large tertiary cancer centre, from 1996 to 2017. Clinical data were obtained from electronic care records, laboratory and pharmacy databases. Survival analysis was estimated using the Kaplan-Meier method and standard log-rank test.
Results
We identified 47 patients, 46 of which were included in the whole cohort analysis (1 was excluded due to insufficient data). The median age at diagnosis was 65 years (35–83) and 63% were male. There were 24 (52%) PMF, 9 (20%) PET-MF, 11 (24%) PPV- MF, 2 (4%) post-myeloproliferative neoplasm-unclassified (PMPN)-MF patients, comprising 35% high-risk, 28% intermediate-2 (int- 2), 35% intermediate-1 (int-1) and 2% low risk patients. A driver mutation was detected in 89% (78% JAK 2+; 11% CALR+). The whole cohort median survival was 8.5 years (0.5–21.5). Of the 46 patients, 28 (61%) received RUX. Five were excluded from further analysis (2 had received another JAK inhibitor; 3 had stem cell transplantation). Of the remaining 41, 24 (59%) received RUX; 10 (24%) as first-line therapy. Baseline demographics were similar between patients treated with RUX or BAT. The RUX group comprised 29% high-, 38% int-2 and 33% int-1 risk patients, and had a significant 5-year overall survival (OS) advantage from time of diagnosis vs BAT; 77% (95% CI 53–90) vs. 57% (95% CI 27–79); p=0.044. Median survival in the BAT group was 6.3 years for int-1, 1.4 years for int-2, and 2.1 years for high-risk patients. Median survival in the RUX group was 1.8 years for high-risk and was not reached for int-1 and int-2 risk patients. There was no survival difference between int-1 and int-2 risk RUX patients; however, int-1 risk RUX patients had a notable survival advantage vs int-1 risk BAT patients; 5y OS 100% vs 86% (95% CI 33–98); p=0.045. In the RUX group, 1y OS was 82% (58–93) with median follow-up of 14 months (1– 50). The estimated discontinuation rate was 31% (95% CI 16–55) at 1 year. At the time of analysis, 10 patients had stopped RUX; 5 died, 4 progressed/no response, and 1 due to adverse effects (AE). Two (8%) transformed to acute myeloid leukaemia. The most common grade 3/4 AEs were thrombocytopaenia (25%) and anaemia (54%), with 33% requiring dose reduction or interruption. The most common non-haematological AEs were infection (42%). Data collection of spleen response and symptom control is underway but incomplete.
Conclusion
In summary, our whole cohort data demonstrate similar outcomes for MF patients treated in NI compared with contemporary clinical trials. Notably, there was a significant survival advantage for patients treated with RUX vs BAT in all risk groups, including intermediate-1 risk patients who at present do not meet funding criteria to receive RUX. This data must be interpreted with caution due to the limited follow-up but it suggests a potentially unmet clinical need in lower-risk MF patients that requires further study.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Clinical data, Janus Kinase inhibitor, Myelofibrosis, Ruxolitinib