IMPACT OF JAK2 AND CALR MUTATIONS ON THE DISEASE FEATURES AND OUTCOME AMONG PATIENTS WITH PRIMARY MYELOFIBROSIS OR ESSENTIAL THROMBOCYTHEMIA TREATED WITH STANDARD OF CARE (INCLUDING RUXOLITINIB)
(Abstract release date: 05/19/16)
EHA Library. Hupfer V. 06/09/16; 132905; E1356
Disclosure(s): No relevant conflicts of interest to disclose.
Ms. Valerie Hupfer
Contributions
Contributions
Abstract
Abstract: E1356
Type: Eposter Presentation
Background
Primary myelofibrosis (PMF) and essential thrombocythemia (ET) share the same mutations in JAK2 and CALR but differ in their clinical features and outcomes.
Aims
Here, we assessed the impact of JAK2 and CALR mutations on the clinical features at diagnosis and on the outcome of patients with PMF or ET treated with standard of care including the JAK2 inhibitor ruxolitinib.
Methods
We studied the clinical and genetic features of 212 patients (median age at diagnosis, 60 years [y]; range, 22-93 y) with PMF (n=93), ET (n=84) or PMF/ET (n=35). Diagnosis was made applying the WHO 2008 criteria, with no clear assignment to PMF or ET possible for patients with PMF/ET. CALR mutations were primarily assessed in patients without JAK2 V617F. Median follow-up time was 5.9 y. Associations were assessed using the Mann-Whitney U-Test for continuous and Fisher's exact test for categorical variables. Overall survival (OS) and leukemia-free-survival (LFS) were estimated using the Kaplan-Meier-method and compared using the log-rank-test.
Results
In the entire cohort of 212 patients, 58.6% carried a JAK2 V617F and, of the JAK2 V617F negative patients tested for CALR mutations, 38.3% had a CALR type 1/type 1-like and 25.5% a type 2/type 2-like mutation. Patients with CALR mutations were of younger age at diagnosis (p=0.003) and of predominantly male gender in comparison to JAK2 V617F positive patients (58.8% vs. 48.8%). Patients with CALR mutations tended to present more often with splenomegaly at diagnosis than patients with JAK2 V617F (p=0.19). Considering ET patients only, patients with JAK2 V617F presented with higher white blood counts compared to those with CALR mutation (p=0.0006). Among the PMF patients, those with CALR mutations had higher platelet counts at diagnosis than those with JAK2 V617F (p=0.043). Of the 212 patients, 77.4% received treatment specific for PMF or ET (excluding aspirin); 58% had hydroxyurea, 12.8% received an allogeneic blood stem cell transplantation. Regarding the outcomes, patients with JAK2 V617F had slightly higher rates of thromboembolic events compared to those with CALR mutations (35.8% vs. 23.5%, p=0.21). There were significant differences in OS and LFS in the PMF cohort with patients with CALR mutations having better OS (p=0.047; 10y rates 88.9% vs. 65.1%) and LFS (p=0.049) than patients with JAK2 V617F; the difference in the OS remained significant among patients aged >60y (p=0.02). Among the ET patients, we did not observe differences in OS or LFS according to the JAK2 V617F or CALR mutation status. Importantly, PMF patients with CALR mutations had a similar risk profile in terms of OS as ET patients (p=0.71), implicating that CALR mutations attenuate the generally accepted adverse prognosis associated with the diagnosis of PMF as opposed to that of ET. Among the 24 PMF patients treated with ruxolitinib, there were no significant differences in the reduction of spleen size, changes in blood counts or OS between patients with JAK2 V617F or CALR mutations, suggesting that response to ruxolitinib is independent of the JAK2 and CALR mutation status.
Conclusion
JAK2 V617F and CALR mutations are associated with distinct clinical features in ET and PMF. Patients with PMF and CALR mutation have an OS better than that of PMF patients with JAK2 V617F and similar to that of patients with ET. The treatment response to ruxolitinib is similar among PMF patients with JAK2 V617F or CALR mutations, which refers to the role of JAK-STAT signaling in both mutation types.
Session topic: E-poster
Keyword(s): Mutation, Myelofibrosis, Ruxolitinib, Thrombocythemia
Type: Eposter Presentation
Background
Primary myelofibrosis (PMF) and essential thrombocythemia (ET) share the same mutations in JAK2 and CALR but differ in their clinical features and outcomes.
Aims
Here, we assessed the impact of JAK2 and CALR mutations on the clinical features at diagnosis and on the outcome of patients with PMF or ET treated with standard of care including the JAK2 inhibitor ruxolitinib.
Methods
We studied the clinical and genetic features of 212 patients (median age at diagnosis, 60 years [y]; range, 22-93 y) with PMF (n=93), ET (n=84) or PMF/ET (n=35). Diagnosis was made applying the WHO 2008 criteria, with no clear assignment to PMF or ET possible for patients with PMF/ET. CALR mutations were primarily assessed in patients without JAK2 V617F. Median follow-up time was 5.9 y. Associations were assessed using the Mann-Whitney U-Test for continuous and Fisher's exact test for categorical variables. Overall survival (OS) and leukemia-free-survival (LFS) were estimated using the Kaplan-Meier-method and compared using the log-rank-test.
Results
In the entire cohort of 212 patients, 58.6% carried a JAK2 V617F and, of the JAK2 V617F negative patients tested for CALR mutations, 38.3% had a CALR type 1/type 1-like and 25.5% a type 2/type 2-like mutation. Patients with CALR mutations were of younger age at diagnosis (p=0.003) and of predominantly male gender in comparison to JAK2 V617F positive patients (58.8% vs. 48.8%). Patients with CALR mutations tended to present more often with splenomegaly at diagnosis than patients with JAK2 V617F (p=0.19). Considering ET patients only, patients with JAK2 V617F presented with higher white blood counts compared to those with CALR mutation (p=0.0006). Among the PMF patients, those with CALR mutations had higher platelet counts at diagnosis than those with JAK2 V617F (p=0.043). Of the 212 patients, 77.4% received treatment specific for PMF or ET (excluding aspirin); 58% had hydroxyurea, 12.8% received an allogeneic blood stem cell transplantation. Regarding the outcomes, patients with JAK2 V617F had slightly higher rates of thromboembolic events compared to those with CALR mutations (35.8% vs. 23.5%, p=0.21). There were significant differences in OS and LFS in the PMF cohort with patients with CALR mutations having better OS (p=0.047; 10y rates 88.9% vs. 65.1%) and LFS (p=0.049) than patients with JAK2 V617F; the difference in the OS remained significant among patients aged >60y (p=0.02). Among the ET patients, we did not observe differences in OS or LFS according to the JAK2 V617F or CALR mutation status. Importantly, PMF patients with CALR mutations had a similar risk profile in terms of OS as ET patients (p=0.71), implicating that CALR mutations attenuate the generally accepted adverse prognosis associated with the diagnosis of PMF as opposed to that of ET. Among the 24 PMF patients treated with ruxolitinib, there were no significant differences in the reduction of spleen size, changes in blood counts or OS between patients with JAK2 V617F or CALR mutations, suggesting that response to ruxolitinib is independent of the JAK2 and CALR mutation status.
Conclusion
JAK2 V617F and CALR mutations are associated with distinct clinical features in ET and PMF. Patients with PMF and CALR mutation have an OS better than that of PMF patients with JAK2 V617F and similar to that of patients with ET. The treatment response to ruxolitinib is similar among PMF patients with JAK2 V617F or CALR mutations, which refers to the role of JAK-STAT signaling in both mutation types.
Session topic: E-poster
Keyword(s): Mutation, Myelofibrosis, Ruxolitinib, Thrombocythemia
Abstract: E1356
Type: Eposter Presentation
Background
Primary myelofibrosis (PMF) and essential thrombocythemia (ET) share the same mutations in JAK2 and CALR but differ in their clinical features and outcomes.
Aims
Here, we assessed the impact of JAK2 and CALR mutations on the clinical features at diagnosis and on the outcome of patients with PMF or ET treated with standard of care including the JAK2 inhibitor ruxolitinib.
Methods
We studied the clinical and genetic features of 212 patients (median age at diagnosis, 60 years [y]; range, 22-93 y) with PMF (n=93), ET (n=84) or PMF/ET (n=35). Diagnosis was made applying the WHO 2008 criteria, with no clear assignment to PMF or ET possible for patients with PMF/ET. CALR mutations were primarily assessed in patients without JAK2 V617F. Median follow-up time was 5.9 y. Associations were assessed using the Mann-Whitney U-Test for continuous and Fisher's exact test for categorical variables. Overall survival (OS) and leukemia-free-survival (LFS) were estimated using the Kaplan-Meier-method and compared using the log-rank-test.
Results
In the entire cohort of 212 patients, 58.6% carried a JAK2 V617F and, of the JAK2 V617F negative patients tested for CALR mutations, 38.3% had a CALR type 1/type 1-like and 25.5% a type 2/type 2-like mutation. Patients with CALR mutations were of younger age at diagnosis (p=0.003) and of predominantly male gender in comparison to JAK2 V617F positive patients (58.8% vs. 48.8%). Patients with CALR mutations tended to present more often with splenomegaly at diagnosis than patients with JAK2 V617F (p=0.19). Considering ET patients only, patients with JAK2 V617F presented with higher white blood counts compared to those with CALR mutation (p=0.0006). Among the PMF patients, those with CALR mutations had higher platelet counts at diagnosis than those with JAK2 V617F (p=0.043). Of the 212 patients, 77.4% received treatment specific for PMF or ET (excluding aspirin); 58% had hydroxyurea, 12.8% received an allogeneic blood stem cell transplantation. Regarding the outcomes, patients with JAK2 V617F had slightly higher rates of thromboembolic events compared to those with CALR mutations (35.8% vs. 23.5%, p=0.21). There were significant differences in OS and LFS in the PMF cohort with patients with CALR mutations having better OS (p=0.047; 10y rates 88.9% vs. 65.1%) and LFS (p=0.049) than patients with JAK2 V617F; the difference in the OS remained significant among patients aged >60y (p=0.02). Among the ET patients, we did not observe differences in OS or LFS according to the JAK2 V617F or CALR mutation status. Importantly, PMF patients with CALR mutations had a similar risk profile in terms of OS as ET patients (p=0.71), implicating that CALR mutations attenuate the generally accepted adverse prognosis associated with the diagnosis of PMF as opposed to that of ET. Among the 24 PMF patients treated with ruxolitinib, there were no significant differences in the reduction of spleen size, changes in blood counts or OS between patients with JAK2 V617F or CALR mutations, suggesting that response to ruxolitinib is independent of the JAK2 and CALR mutation status.
Conclusion
JAK2 V617F and CALR mutations are associated with distinct clinical features in ET and PMF. Patients with PMF and CALR mutation have an OS better than that of PMF patients with JAK2 V617F and similar to that of patients with ET. The treatment response to ruxolitinib is similar among PMF patients with JAK2 V617F or CALR mutations, which refers to the role of JAK-STAT signaling in both mutation types.
Session topic: E-poster
Keyword(s): Mutation, Myelofibrosis, Ruxolitinib, Thrombocythemia
Type: Eposter Presentation
Background
Primary myelofibrosis (PMF) and essential thrombocythemia (ET) share the same mutations in JAK2 and CALR but differ in their clinical features and outcomes.
Aims
Here, we assessed the impact of JAK2 and CALR mutations on the clinical features at diagnosis and on the outcome of patients with PMF or ET treated with standard of care including the JAK2 inhibitor ruxolitinib.
Methods
We studied the clinical and genetic features of 212 patients (median age at diagnosis, 60 years [y]; range, 22-93 y) with PMF (n=93), ET (n=84) or PMF/ET (n=35). Diagnosis was made applying the WHO 2008 criteria, with no clear assignment to PMF or ET possible for patients with PMF/ET. CALR mutations were primarily assessed in patients without JAK2 V617F. Median follow-up time was 5.9 y. Associations were assessed using the Mann-Whitney U-Test for continuous and Fisher's exact test for categorical variables. Overall survival (OS) and leukemia-free-survival (LFS) were estimated using the Kaplan-Meier-method and compared using the log-rank-test.
Results
In the entire cohort of 212 patients, 58.6% carried a JAK2 V617F and, of the JAK2 V617F negative patients tested for CALR mutations, 38.3% had a CALR type 1/type 1-like and 25.5% a type 2/type 2-like mutation. Patients with CALR mutations were of younger age at diagnosis (p=0.003) and of predominantly male gender in comparison to JAK2 V617F positive patients (58.8% vs. 48.8%). Patients with CALR mutations tended to present more often with splenomegaly at diagnosis than patients with JAK2 V617F (p=0.19). Considering ET patients only, patients with JAK2 V617F presented with higher white blood counts compared to those with CALR mutation (p=0.0006). Among the PMF patients, those with CALR mutations had higher platelet counts at diagnosis than those with JAK2 V617F (p=0.043). Of the 212 patients, 77.4% received treatment specific for PMF or ET (excluding aspirin); 58% had hydroxyurea, 12.8% received an allogeneic blood stem cell transplantation. Regarding the outcomes, patients with JAK2 V617F had slightly higher rates of thromboembolic events compared to those with CALR mutations (35.8% vs. 23.5%, p=0.21). There were significant differences in OS and LFS in the PMF cohort with patients with CALR mutations having better OS (p=0.047; 10y rates 88.9% vs. 65.1%) and LFS (p=0.049) than patients with JAK2 V617F; the difference in the OS remained significant among patients aged >60y (p=0.02). Among the ET patients, we did not observe differences in OS or LFS according to the JAK2 V617F or CALR mutation status. Importantly, PMF patients with CALR mutations had a similar risk profile in terms of OS as ET patients (p=0.71), implicating that CALR mutations attenuate the generally accepted adverse prognosis associated with the diagnosis of PMF as opposed to that of ET. Among the 24 PMF patients treated with ruxolitinib, there were no significant differences in the reduction of spleen size, changes in blood counts or OS between patients with JAK2 V617F or CALR mutations, suggesting that response to ruxolitinib is independent of the JAK2 and CALR mutation status.
Conclusion
JAK2 V617F and CALR mutations are associated with distinct clinical features in ET and PMF. Patients with PMF and CALR mutation have an OS better than that of PMF patients with JAK2 V617F and similar to that of patients with ET. The treatment response to ruxolitinib is similar among PMF patients with JAK2 V617F or CALR mutations, which refers to the role of JAK-STAT signaling in both mutation types.
Session topic: E-poster
Keyword(s): Mutation, Myelofibrosis, Ruxolitinib, Thrombocythemia
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