SAFETY AND EFFICACY OF RUXOLITINIB IN CLINICAL PRACTICE FOR PRIMARY AND SECONDARY MYELOFIBROSIS
(Abstract release date: 05/19/16)
EHA Library. Breccia M. 06/09/16; 134921; PB2021
Dr. Massimo Breccia
Contributions
Contributions
Abstract
Abstract: PB2021
Type: Publication Only
Background
Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Reduction of spleen volume, improvement of constitutional symptoms and improved quality of life have been reported as major findings in sponsored randomized clinical trials.
Aims
Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials.
Methods
Patients were collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.
Results
There were 45 males and 53 females, median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as evolution from a previous MPN: 31 after Polycythemia Vera, 20 after Essential Thrombocythemia and 2 were not specified. Median splenomegaly at baseline was 6 cm. At baseline, IPSS stratification revealed 4 patients with low risk, 27 with intermediate-1 risk, 42 as intermediate-2 and 23 as high risk. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline and out of 80 patients tested, 58 (72%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. All patients at the time of treatment were intermediate-2/high risk according to IPSS. Hematological parameters pre-treatment were: median haemoglobin level 10.4 gr/dl, median WBC count 11 x 109/l, median platelet count 239 x 109/l. Median splenomegaly pre-treatment was 10 cm. As regards initial daily dose, according to platelet count, 5 patients started with 5 mg BID, 7 patients with 10 mg BID, 26 patients with 15 mg BID and 60 patients with 20 mg BID, with a median initial daily dose of 20 mg BID. Fifty-eight patients (59%) required a dose modification during the first 3 months, which consisted in a dose reduction due to haematological toxicity in the majority of cases. After 24 weeks of treatment, 48% of patients experienced a clinical benefit with some degree of reduction in spleen volume: in particular, according to revised IWG-MRT criteria, 5 patients (5%) achieved a complete response (CR), 8 patients (8%) a partial response, 6 (6%) a clinical improvement (CI), 28 (28.5%) a spleen response, whereas 25 patients did not achieve any response and 24 were not evaluable. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug (8 for toxicity, 4 for progression, 4 lack of efficacy, 1 patient underwent BMT, 1 second neoplasia, 3 deaths).
Conclusion
The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms.
Session topic: E-poster
Keyword(s): Myelofibrosis, Ruxolitinib
Type: Publication Only
Background
Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Reduction of spleen volume, improvement of constitutional symptoms and improved quality of life have been reported as major findings in sponsored randomized clinical trials.
Aims
Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials.
Methods
Patients were collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.
Results
There were 45 males and 53 females, median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as evolution from a previous MPN: 31 after Polycythemia Vera, 20 after Essential Thrombocythemia and 2 were not specified. Median splenomegaly at baseline was 6 cm. At baseline, IPSS stratification revealed 4 patients with low risk, 27 with intermediate-1 risk, 42 as intermediate-2 and 23 as high risk. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline and out of 80 patients tested, 58 (72%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. All patients at the time of treatment were intermediate-2/high risk according to IPSS. Hematological parameters pre-treatment were: median haemoglobin level 10.4 gr/dl, median WBC count 11 x 109/l, median platelet count 239 x 109/l. Median splenomegaly pre-treatment was 10 cm. As regards initial daily dose, according to platelet count, 5 patients started with 5 mg BID, 7 patients with 10 mg BID, 26 patients with 15 mg BID and 60 patients with 20 mg BID, with a median initial daily dose of 20 mg BID. Fifty-eight patients (59%) required a dose modification during the first 3 months, which consisted in a dose reduction due to haematological toxicity in the majority of cases. After 24 weeks of treatment, 48% of patients experienced a clinical benefit with some degree of reduction in spleen volume: in particular, according to revised IWG-MRT criteria, 5 patients (5%) achieved a complete response (CR), 8 patients (8%) a partial response, 6 (6%) a clinical improvement (CI), 28 (28.5%) a spleen response, whereas 25 patients did not achieve any response and 24 were not evaluable. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug (8 for toxicity, 4 for progression, 4 lack of efficacy, 1 patient underwent BMT, 1 second neoplasia, 3 deaths).
Conclusion
The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms.
Session topic: E-poster
Keyword(s): Myelofibrosis, Ruxolitinib
Abstract: PB2021
Type: Publication Only
Background
Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Reduction of spleen volume, improvement of constitutional symptoms and improved quality of life have been reported as major findings in sponsored randomized clinical trials.
Aims
Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials.
Methods
Patients were collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.
Results
There were 45 males and 53 females, median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as evolution from a previous MPN: 31 after Polycythemia Vera, 20 after Essential Thrombocythemia and 2 were not specified. Median splenomegaly at baseline was 6 cm. At baseline, IPSS stratification revealed 4 patients with low risk, 27 with intermediate-1 risk, 42 as intermediate-2 and 23 as high risk. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline and out of 80 patients tested, 58 (72%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. All patients at the time of treatment were intermediate-2/high risk according to IPSS. Hematological parameters pre-treatment were: median haemoglobin level 10.4 gr/dl, median WBC count 11 x 109/l, median platelet count 239 x 109/l. Median splenomegaly pre-treatment was 10 cm. As regards initial daily dose, according to platelet count, 5 patients started with 5 mg BID, 7 patients with 10 mg BID, 26 patients with 15 mg BID and 60 patients with 20 mg BID, with a median initial daily dose of 20 mg BID. Fifty-eight patients (59%) required a dose modification during the first 3 months, which consisted in a dose reduction due to haematological toxicity in the majority of cases. After 24 weeks of treatment, 48% of patients experienced a clinical benefit with some degree of reduction in spleen volume: in particular, according to revised IWG-MRT criteria, 5 patients (5%) achieved a complete response (CR), 8 patients (8%) a partial response, 6 (6%) a clinical improvement (CI), 28 (28.5%) a spleen response, whereas 25 patients did not achieve any response and 24 were not evaluable. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug (8 for toxicity, 4 for progression, 4 lack of efficacy, 1 patient underwent BMT, 1 second neoplasia, 3 deaths).
Conclusion
The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms.
Session topic: E-poster
Keyword(s): Myelofibrosis, Ruxolitinib
Type: Publication Only
Background
Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Reduction of spleen volume, improvement of constitutional symptoms and improved quality of life have been reported as major findings in sponsored randomized clinical trials.
Aims
Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials.
Methods
Patients were collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.
Results
There were 45 males and 53 females, median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as evolution from a previous MPN: 31 after Polycythemia Vera, 20 after Essential Thrombocythemia and 2 were not specified. Median splenomegaly at baseline was 6 cm. At baseline, IPSS stratification revealed 4 patients with low risk, 27 with intermediate-1 risk, 42 as intermediate-2 and 23 as high risk. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline and out of 80 patients tested, 58 (72%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. All patients at the time of treatment were intermediate-2/high risk according to IPSS. Hematological parameters pre-treatment were: median haemoglobin level 10.4 gr/dl, median WBC count 11 x 109/l, median platelet count 239 x 109/l. Median splenomegaly pre-treatment was 10 cm. As regards initial daily dose, according to platelet count, 5 patients started with 5 mg BID, 7 patients with 10 mg BID, 26 patients with 15 mg BID and 60 patients with 20 mg BID, with a median initial daily dose of 20 mg BID. Fifty-eight patients (59%) required a dose modification during the first 3 months, which consisted in a dose reduction due to haematological toxicity in the majority of cases. After 24 weeks of treatment, 48% of patients experienced a clinical benefit with some degree of reduction in spleen volume: in particular, according to revised IWG-MRT criteria, 5 patients (5%) achieved a complete response (CR), 8 patients (8%) a partial response, 6 (6%) a clinical improvement (CI), 28 (28.5%) a spleen response, whereas 25 patients did not achieve any response and 24 were not evaluable. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug (8 for toxicity, 4 for progression, 4 lack of efficacy, 1 patient underwent BMT, 1 second neoplasia, 3 deaths).
Conclusion
The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms.
Session topic: E-poster
Keyword(s): Myelofibrosis, Ruxolitinib
{{ help_message }}
{{filter}}