RUXOLITINIB IN MYELOFIBROSIS: A TWO-CENTRE EXPERIENCE
(Abstract release date: 05/19/16)
EHA Library. Russell J. 06/09/16; 134934; PB2034
Dr. James Russell
Contributions
Contributions
Abstract
Abstract: PB2034
Type: Publication Only
Background
Ruxolitinib, an oral Janus Kinase (JAK)1 and JAK2 inhibitor, was approved in the European Union in August 2012 for treating disease-related splenomegaly and constitutional symptoms in adults with primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF), following the results of two phase III trials (COMFORT-I and COMFORT-II). The James Paget University Hospital and Ipswich Hospital have treated 31 MF patients (24 and seven, respectively) with ruxolitinib since March 2013.
Aims
To assess the efficacy and safety of ruxolitinib in MF in the clinical setting.
Methods
Retrospective analysis of 31 MF patients treated with ruxolitinib from March 2013 to February 2016 at the James Paget University Hospital and Ipswich Hospital. Patients with greater than three months’ follow-up were included.
Results
The patient group was 58% male, with a median age of 69 years (range 58–92). Ruxolitinib was first-line therapy in eight patients (26%) and second-line in 23 (74%). The indication for treatment was painful splenomegaly in 17 (55%) patients, constitutional symptoms in 13 (42%) and portal hypertension in one (3%). Fifteen patients (48%) had PMF, ten (32%) had PPV-MF, five (16%) had PET-MF and one (3%) had post-myeloproliferative disorder (unclassified)-MF. Seventeen (55%) patients had an International Prognostic Scoring System (IPSS) score of three (high risk), 13 (42%) had an IPSS score of two (intermediate risk-2), and one (3%) had an IPSS score of one (intermediate risk-1). Twenty-two patients (71%) were JAK2 V617F positive and one (3%) had a CALR mutation. The median duration of treatment was 17 months (range 5-35). Twenty-six patients (84%) had a therapeutic response. Of the 17 with painful splenomegaly, eight (47%) had >50% reduction in spleen length, six (35%) had <50%, and three (18%) had no change. Nonhaematologic adverse events (AEs) were uncommon and low grade. Weight gain was the most common, occurring in 25 (81%) patients. Minor infections, including oral candidiasis, were also common and easily treated. One patient, however, developed Aspergillus pneumonia after 17 months and died. The most common haematologic AEs were anaemia and thrombocytopaenia. All patients developed anaemia; nine (29%) required transfusions and 12 (39%) required erythropoietin. Nine patients (29%) developed thrombocytopaenia (grade 3/4 in three patients) which was managed by dose reduction, or drug interruption, without permanent discontinuation. Four patients (16%) progressed to acute myeloid leukaemia (AML) after a median of four months (range 3-15) and died. Another patient died after losing therapeutic response at 16 months. Our leukaemia-free survival, progression-free survival, and overall survival rate is 81% vs 80% in COMFORT-II at three years. Currently, 25 patients (81%) remain on treatment.
Conclusion
In our experience, overall response rate and tolerability to ruxolitinib was similar to the COMFORT-II trial. The most common nonhaematologic AEs were weight gain and minor infections. Furthermore, in many cases weight gain was a desired outcome attributable to improved constitutional symptoms, spleen size, and nutritional status. Conversely, haematologic AE rates may be higher than in the trial setting. Anaemia was observed in all patients and thrombocytopaenia commonly required dose adjustments. There was also a higher than expected incidence of transformation to AML. Most AEs, however, were low grade and readily managed. The majority of patients remain on active treatment.
Session topic: E-poster
Keyword(s): Clinical data, Janus Kinase inhibitor, Myelofibrosis, Ruxolitinib
Type: Publication Only
Background
Ruxolitinib, an oral Janus Kinase (JAK)1 and JAK2 inhibitor, was approved in the European Union in August 2012 for treating disease-related splenomegaly and constitutional symptoms in adults with primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF), following the results of two phase III trials (COMFORT-I and COMFORT-II). The James Paget University Hospital and Ipswich Hospital have treated 31 MF patients (24 and seven, respectively) with ruxolitinib since March 2013.
Aims
To assess the efficacy and safety of ruxolitinib in MF in the clinical setting.
Methods
Retrospective analysis of 31 MF patients treated with ruxolitinib from March 2013 to February 2016 at the James Paget University Hospital and Ipswich Hospital. Patients with greater than three months’ follow-up were included.
Results
The patient group was 58% male, with a median age of 69 years (range 58–92). Ruxolitinib was first-line therapy in eight patients (26%) and second-line in 23 (74%). The indication for treatment was painful splenomegaly in 17 (55%) patients, constitutional symptoms in 13 (42%) and portal hypertension in one (3%). Fifteen patients (48%) had PMF, ten (32%) had PPV-MF, five (16%) had PET-MF and one (3%) had post-myeloproliferative disorder (unclassified)-MF. Seventeen (55%) patients had an International Prognostic Scoring System (IPSS) score of three (high risk), 13 (42%) had an IPSS score of two (intermediate risk-2), and one (3%) had an IPSS score of one (intermediate risk-1). Twenty-two patients (71%) were JAK2 V617F positive and one (3%) had a CALR mutation. The median duration of treatment was 17 months (range 5-35). Twenty-six patients (84%) had a therapeutic response. Of the 17 with painful splenomegaly, eight (47%) had >50% reduction in spleen length, six (35%) had <50%, and three (18%) had no change. Nonhaematologic adverse events (AEs) were uncommon and low grade. Weight gain was the most common, occurring in 25 (81%) patients. Minor infections, including oral candidiasis, were also common and easily treated. One patient, however, developed Aspergillus pneumonia after 17 months and died. The most common haematologic AEs were anaemia and thrombocytopaenia. All patients developed anaemia; nine (29%) required transfusions and 12 (39%) required erythropoietin. Nine patients (29%) developed thrombocytopaenia (grade 3/4 in three patients) which was managed by dose reduction, or drug interruption, without permanent discontinuation. Four patients (16%) progressed to acute myeloid leukaemia (AML) after a median of four months (range 3-15) and died. Another patient died after losing therapeutic response at 16 months. Our leukaemia-free survival, progression-free survival, and overall survival rate is 81% vs 80% in COMFORT-II at three years. Currently, 25 patients (81%) remain on treatment.
Conclusion
In our experience, overall response rate and tolerability to ruxolitinib was similar to the COMFORT-II trial. The most common nonhaematologic AEs were weight gain and minor infections. Furthermore, in many cases weight gain was a desired outcome attributable to improved constitutional symptoms, spleen size, and nutritional status. Conversely, haematologic AE rates may be higher than in the trial setting. Anaemia was observed in all patients and thrombocytopaenia commonly required dose adjustments. There was also a higher than expected incidence of transformation to AML. Most AEs, however, were low grade and readily managed. The majority of patients remain on active treatment.
Session topic: E-poster
Keyword(s): Clinical data, Janus Kinase inhibitor, Myelofibrosis, Ruxolitinib
Abstract: PB2034
Type: Publication Only
Background
Ruxolitinib, an oral Janus Kinase (JAK)1 and JAK2 inhibitor, was approved in the European Union in August 2012 for treating disease-related splenomegaly and constitutional symptoms in adults with primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF), following the results of two phase III trials (COMFORT-I and COMFORT-II). The James Paget University Hospital and Ipswich Hospital have treated 31 MF patients (24 and seven, respectively) with ruxolitinib since March 2013.
Aims
To assess the efficacy and safety of ruxolitinib in MF in the clinical setting.
Methods
Retrospective analysis of 31 MF patients treated with ruxolitinib from March 2013 to February 2016 at the James Paget University Hospital and Ipswich Hospital. Patients with greater than three months’ follow-up were included.
Results
The patient group was 58% male, with a median age of 69 years (range 58–92). Ruxolitinib was first-line therapy in eight patients (26%) and second-line in 23 (74%). The indication for treatment was painful splenomegaly in 17 (55%) patients, constitutional symptoms in 13 (42%) and portal hypertension in one (3%). Fifteen patients (48%) had PMF, ten (32%) had PPV-MF, five (16%) had PET-MF and one (3%) had post-myeloproliferative disorder (unclassified)-MF. Seventeen (55%) patients had an International Prognostic Scoring System (IPSS) score of three (high risk), 13 (42%) had an IPSS score of two (intermediate risk-2), and one (3%) had an IPSS score of one (intermediate risk-1). Twenty-two patients (71%) were JAK2 V617F positive and one (3%) had a CALR mutation. The median duration of treatment was 17 months (range 5-35). Twenty-six patients (84%) had a therapeutic response. Of the 17 with painful splenomegaly, eight (47%) had >50% reduction in spleen length, six (35%) had <50%, and three (18%) had no change. Nonhaematologic adverse events (AEs) were uncommon and low grade. Weight gain was the most common, occurring in 25 (81%) patients. Minor infections, including oral candidiasis, were also common and easily treated. One patient, however, developed Aspergillus pneumonia after 17 months and died. The most common haematologic AEs were anaemia and thrombocytopaenia. All patients developed anaemia; nine (29%) required transfusions and 12 (39%) required erythropoietin. Nine patients (29%) developed thrombocytopaenia (grade 3/4 in three patients) which was managed by dose reduction, or drug interruption, without permanent discontinuation. Four patients (16%) progressed to acute myeloid leukaemia (AML) after a median of four months (range 3-15) and died. Another patient died after losing therapeutic response at 16 months. Our leukaemia-free survival, progression-free survival, and overall survival rate is 81% vs 80% in COMFORT-II at three years. Currently, 25 patients (81%) remain on treatment.
Conclusion
In our experience, overall response rate and tolerability to ruxolitinib was similar to the COMFORT-II trial. The most common nonhaematologic AEs were weight gain and minor infections. Furthermore, in many cases weight gain was a desired outcome attributable to improved constitutional symptoms, spleen size, and nutritional status. Conversely, haematologic AE rates may be higher than in the trial setting. Anaemia was observed in all patients and thrombocytopaenia commonly required dose adjustments. There was also a higher than expected incidence of transformation to AML. Most AEs, however, were low grade and readily managed. The majority of patients remain on active treatment.
Session topic: E-poster
Keyword(s): Clinical data, Janus Kinase inhibitor, Myelofibrosis, Ruxolitinib
Type: Publication Only
Background
Ruxolitinib, an oral Janus Kinase (JAK)1 and JAK2 inhibitor, was approved in the European Union in August 2012 for treating disease-related splenomegaly and constitutional symptoms in adults with primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF), following the results of two phase III trials (COMFORT-I and COMFORT-II). The James Paget University Hospital and Ipswich Hospital have treated 31 MF patients (24 and seven, respectively) with ruxolitinib since March 2013.
Aims
To assess the efficacy and safety of ruxolitinib in MF in the clinical setting.
Methods
Retrospective analysis of 31 MF patients treated with ruxolitinib from March 2013 to February 2016 at the James Paget University Hospital and Ipswich Hospital. Patients with greater than three months’ follow-up were included.
Results
The patient group was 58% male, with a median age of 69 years (range 58–92). Ruxolitinib was first-line therapy in eight patients (26%) and second-line in 23 (74%). The indication for treatment was painful splenomegaly in 17 (55%) patients, constitutional symptoms in 13 (42%) and portal hypertension in one (3%). Fifteen patients (48%) had PMF, ten (32%) had PPV-MF, five (16%) had PET-MF and one (3%) had post-myeloproliferative disorder (unclassified)-MF. Seventeen (55%) patients had an International Prognostic Scoring System (IPSS) score of three (high risk), 13 (42%) had an IPSS score of two (intermediate risk-2), and one (3%) had an IPSS score of one (intermediate risk-1). Twenty-two patients (71%) were JAK2 V617F positive and one (3%) had a CALR mutation. The median duration of treatment was 17 months (range 5-35). Twenty-six patients (84%) had a therapeutic response. Of the 17 with painful splenomegaly, eight (47%) had >50% reduction in spleen length, six (35%) had <50%, and three (18%) had no change. Nonhaematologic adverse events (AEs) were uncommon and low grade. Weight gain was the most common, occurring in 25 (81%) patients. Minor infections, including oral candidiasis, were also common and easily treated. One patient, however, developed Aspergillus pneumonia after 17 months and died. The most common haematologic AEs were anaemia and thrombocytopaenia. All patients developed anaemia; nine (29%) required transfusions and 12 (39%) required erythropoietin. Nine patients (29%) developed thrombocytopaenia (grade 3/4 in three patients) which was managed by dose reduction, or drug interruption, without permanent discontinuation. Four patients (16%) progressed to acute myeloid leukaemia (AML) after a median of four months (range 3-15) and died. Another patient died after losing therapeutic response at 16 months. Our leukaemia-free survival, progression-free survival, and overall survival rate is 81% vs 80% in COMFORT-II at three years. Currently, 25 patients (81%) remain on treatment.
Conclusion
In our experience, overall response rate and tolerability to ruxolitinib was similar to the COMFORT-II trial. The most common nonhaematologic AEs were weight gain and minor infections. Furthermore, in many cases weight gain was a desired outcome attributable to improved constitutional symptoms, spleen size, and nutritional status. Conversely, haematologic AE rates may be higher than in the trial setting. Anaemia was observed in all patients and thrombocytopaenia commonly required dose adjustments. There was also a higher than expected incidence of transformation to AML. Most AEs, however, were low grade and readily managed. The majority of patients remain on active treatment.
Session topic: E-poster
Keyword(s): Clinical data, Janus Kinase inhibitor, Myelofibrosis, Ruxolitinib
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