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The Revised International Prognostic Scoring System is superior to other commonly used systems when it comes to predicting leukemic evolution and survival in patients with myelodysplastic syndromes and may therefore help guide treatment decisions, new data suggest.
Dr. Maria Teresa Voso and her colleagues validated the new system and tested its predictive ability against two other commonly used systems – the classic International Prognostic Scoring System (IPSS) and the World Health Organization’s Prognostic Scoring System (WPSS) – in a retrospective cohort study of 380 patients treated between 2001 and 2011.
Compared with these others systems, which rely mainly on disease-related factors, the Revised IPSS (IPSS-R) additionally incorporates detailed cytogenetic groupings, the severity of bone marrow infiltration, and the depth of cytopenias.
Study results appearing in the Journal of Clinical Oncology confirmed that the IPSS-R significantly predicted both leukemia-free survival and overall survival in this cohort with myelodysplastic syndromes (MDS), and that it outperformed both of the other systems.
Moreover, the IPSS-R was an independent predictor of leukemia-free survival and overall survival in a multivariate model that included both of these other systems as well as a host of demographic, clinical, and treatment factors, the investigators noted.
For example, compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.
"Our data show that the IPSS-R is an excellent predictor of MDS prognosis in the era of disease-modifying treatments," said Dr. Voso of Università Cattolica del Sacro Cuore, Rome, and her associates (J. Clin. Oncol. 2013;31:2671-7).
"In the future, the integration of comorbidity scores and time-dependent scores, which consider the evolutive nature of MDS, may further address the decision-making process for a correct treatment approach. The early recognition of patients at high risk of progression to aggressive disease may also optimize treatment timing, before worsening of comorbidities," they added.
The patients studied were 182 women and 198 men having a median age of 71 years from the Italian Gruppo Romano Mielodisplasie (GROM) registry, which captures data in unselected patients with MDS starting at the time of initial diagnosis.
The majority of the patients received supportive treatments such as vitamins (24%), erythropoiesis-stimulating agents (49%), and transfusions (58%). A minority received active treatment with lenalidomide (6%), azacitidine (18%), or cytotoxic drugs (2%).
In terms of IPSS-R scores, 38% of the patients fell into the very-low-risk group, 33% into the low-risk group, 18% into the intermediate-risk group, 7% into the high-risk group, and 4% into the very-high-risk group, Dr. Voso and her colleagues said.
With a median follow-up of 2.8 years, the IPSS-R predicted leukemia-free survival (P less than .001) and overall survival (P less than .001), and it was superior to both the classic IPSS and the WPSS in its predictive ability (P less than .001), they wrote.
In a multivariate model that considered all three scoring systems plus a variety of potential confounders (age, lactate dehydrogenase concentration, ferritin concentration, performance status, transfusion dependency, and type of therapy), the IPSS-R score was an independent predictor.
When peers in the intermediate-risk group were used as the comparator, patients had better leukemia-free survival if they fell in the very-low-risk group (hazard ratio [HR], 0.26; P less than .001) or low-risk group (HR, 0.58; P = .02), and patients had poorer leukemia-free survival if they fell in the high-risk group (HR, 1.72; P = .08) or very-high-risk group (HR, 3.26; P = .004).
Similarly, patients had better overall survival if they were in the very-low-risk group (HR, 0.29; P less than .001) or low-risk group (HR, 0.59; P = .04), and patients had poorer overall survival if they were in the high-risk group (HR, 1.67; P = .10) or very-high-risk group (HR, 5.13; P less than .001).
Dr. Voso disclosed receiving honoraria from Celgene.
The IPSS-R has already been validated; however, this article does advance the field in showing the ability of the IPSS-R to retain its predictive abilities in a small cohort of patients treated with disease-modifying agents – a group not previously included in the development or validation of the IPSS-R.
It remains to be seen whether the IPSS-R remains robust in larger cohorts of treated patients, or whether additional revisions to the IPSS-R may be required for treated patients as a group or for specific therapies. This task of determining whether further revisions are needed is already being initiated by the International Working Group.
In practice, the IPSS and IPSS-R are used both to predict survival and to help determine therapeutic approach. The study helps refine our definition of lower and higher risk and starts to substantiate it in treated patients. What remains are questions regarding the best approach for patients in the IPSS-R intermediate-risk category, who are neither lower nor higher risk, as well as the need to validate risk-based approaches prospectively, given that our best data for most MDS management principles remain circumstantial.
Dr. Mikkael A. Sekeres is with the Cleveland Clinic Taussig Cancer Institute. He made his remarks in an accompanying editorial (J. Clin. Oncol. 2013;31:2643-4). Dr. Sekeres disclosed consultancy/advisory roles with Celgene and Amgen.
The IPSS-R has already been validated; however, this article does advance the field in showing the ability of the IPSS-R to retain its predictive abilities in a small cohort of patients treated with disease-modifying agents – a group not previously included in the development or validation of the IPSS-R.
It remains to be seen whether the IPSS-R remains robust in larger cohorts of treated patients, or whether additional revisions to the IPSS-R may be required for treated patients as a group or for specific therapies. This task of determining whether further revisions are needed is already being initiated by the International Working Group.
In practice, the IPSS and IPSS-R are used both to predict survival and to help determine therapeutic approach. The study helps refine our definition of lower and higher risk and starts to substantiate it in treated patients. What remains are questions regarding the best approach for patients in the IPSS-R intermediate-risk category, who are neither lower nor higher risk, as well as the need to validate risk-based approaches prospectively, given that our best data for most MDS management principles remain circumstantial.
Dr. Mikkael A. Sekeres is with the Cleveland Clinic Taussig Cancer Institute. He made his remarks in an accompanying editorial (J. Clin. Oncol. 2013;31:2643-4). Dr. Sekeres disclosed consultancy/advisory roles with Celgene and Amgen.
The IPSS-R has already been validated; however, this article does advance the field in showing the ability of the IPSS-R to retain its predictive abilities in a small cohort of patients treated with disease-modifying agents – a group not previously included in the development or validation of the IPSS-R.
It remains to be seen whether the IPSS-R remains robust in larger cohorts of treated patients, or whether additional revisions to the IPSS-R may be required for treated patients as a group or for specific therapies. This task of determining whether further revisions are needed is already being initiated by the International Working Group.
In practice, the IPSS and IPSS-R are used both to predict survival and to help determine therapeutic approach. The study helps refine our definition of lower and higher risk and starts to substantiate it in treated patients. What remains are questions regarding the best approach for patients in the IPSS-R intermediate-risk category, who are neither lower nor higher risk, as well as the need to validate risk-based approaches prospectively, given that our best data for most MDS management principles remain circumstantial.
Dr. Mikkael A. Sekeres is with the Cleveland Clinic Taussig Cancer Institute. He made his remarks in an accompanying editorial (J. Clin. Oncol. 2013;31:2643-4). Dr. Sekeres disclosed consultancy/advisory roles with Celgene and Amgen.
The Revised International Prognostic Scoring System is superior to other commonly used systems when it comes to predicting leukemic evolution and survival in patients with myelodysplastic syndromes and may therefore help guide treatment decisions, new data suggest.
Dr. Maria Teresa Voso and her colleagues validated the new system and tested its predictive ability against two other commonly used systems – the classic International Prognostic Scoring System (IPSS) and the World Health Organization’s Prognostic Scoring System (WPSS) – in a retrospective cohort study of 380 patients treated between 2001 and 2011.
Compared with these others systems, which rely mainly on disease-related factors, the Revised IPSS (IPSS-R) additionally incorporates detailed cytogenetic groupings, the severity of bone marrow infiltration, and the depth of cytopenias.
Study results appearing in the Journal of Clinical Oncology confirmed that the IPSS-R significantly predicted both leukemia-free survival and overall survival in this cohort with myelodysplastic syndromes (MDS), and that it outperformed both of the other systems.
Moreover, the IPSS-R was an independent predictor of leukemia-free survival and overall survival in a multivariate model that included both of these other systems as well as a host of demographic, clinical, and treatment factors, the investigators noted.
For example, compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.
"Our data show that the IPSS-R is an excellent predictor of MDS prognosis in the era of disease-modifying treatments," said Dr. Voso of Università Cattolica del Sacro Cuore, Rome, and her associates (J. Clin. Oncol. 2013;31:2671-7).
"In the future, the integration of comorbidity scores and time-dependent scores, which consider the evolutive nature of MDS, may further address the decision-making process for a correct treatment approach. The early recognition of patients at high risk of progression to aggressive disease may also optimize treatment timing, before worsening of comorbidities," they added.
The patients studied were 182 women and 198 men having a median age of 71 years from the Italian Gruppo Romano Mielodisplasie (GROM) registry, which captures data in unselected patients with MDS starting at the time of initial diagnosis.
The majority of the patients received supportive treatments such as vitamins (24%), erythropoiesis-stimulating agents (49%), and transfusions (58%). A minority received active treatment with lenalidomide (6%), azacitidine (18%), or cytotoxic drugs (2%).
In terms of IPSS-R scores, 38% of the patients fell into the very-low-risk group, 33% into the low-risk group, 18% into the intermediate-risk group, 7% into the high-risk group, and 4% into the very-high-risk group, Dr. Voso and her colleagues said.
With a median follow-up of 2.8 years, the IPSS-R predicted leukemia-free survival (P less than .001) and overall survival (P less than .001), and it was superior to both the classic IPSS and the WPSS in its predictive ability (P less than .001), they wrote.
In a multivariate model that considered all three scoring systems plus a variety of potential confounders (age, lactate dehydrogenase concentration, ferritin concentration, performance status, transfusion dependency, and type of therapy), the IPSS-R score was an independent predictor.
When peers in the intermediate-risk group were used as the comparator, patients had better leukemia-free survival if they fell in the very-low-risk group (hazard ratio [HR], 0.26; P less than .001) or low-risk group (HR, 0.58; P = .02), and patients had poorer leukemia-free survival if they fell in the high-risk group (HR, 1.72; P = .08) or very-high-risk group (HR, 3.26; P = .004).
Similarly, patients had better overall survival if they were in the very-low-risk group (HR, 0.29; P less than .001) or low-risk group (HR, 0.59; P = .04), and patients had poorer overall survival if they were in the high-risk group (HR, 1.67; P = .10) or very-high-risk group (HR, 5.13; P less than .001).
Dr. Voso disclosed receiving honoraria from Celgene.
The Revised International Prognostic Scoring System is superior to other commonly used systems when it comes to predicting leukemic evolution and survival in patients with myelodysplastic syndromes and may therefore help guide treatment decisions, new data suggest.
Dr. Maria Teresa Voso and her colleagues validated the new system and tested its predictive ability against two other commonly used systems – the classic International Prognostic Scoring System (IPSS) and the World Health Organization’s Prognostic Scoring System (WPSS) – in a retrospective cohort study of 380 patients treated between 2001 and 2011.
Compared with these others systems, which rely mainly on disease-related factors, the Revised IPSS (IPSS-R) additionally incorporates detailed cytogenetic groupings, the severity of bone marrow infiltration, and the depth of cytopenias.
Study results appearing in the Journal of Clinical Oncology confirmed that the IPSS-R significantly predicted both leukemia-free survival and overall survival in this cohort with myelodysplastic syndromes (MDS), and that it outperformed both of the other systems.
Moreover, the IPSS-R was an independent predictor of leukemia-free survival and overall survival in a multivariate model that included both of these other systems as well as a host of demographic, clinical, and treatment factors, the investigators noted.
For example, compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.
"Our data show that the IPSS-R is an excellent predictor of MDS prognosis in the era of disease-modifying treatments," said Dr. Voso of Università Cattolica del Sacro Cuore, Rome, and her associates (J. Clin. Oncol. 2013;31:2671-7).
"In the future, the integration of comorbidity scores and time-dependent scores, which consider the evolutive nature of MDS, may further address the decision-making process for a correct treatment approach. The early recognition of patients at high risk of progression to aggressive disease may also optimize treatment timing, before worsening of comorbidities," they added.
The patients studied were 182 women and 198 men having a median age of 71 years from the Italian Gruppo Romano Mielodisplasie (GROM) registry, which captures data in unselected patients with MDS starting at the time of initial diagnosis.
The majority of the patients received supportive treatments such as vitamins (24%), erythropoiesis-stimulating agents (49%), and transfusions (58%). A minority received active treatment with lenalidomide (6%), azacitidine (18%), or cytotoxic drugs (2%).
In terms of IPSS-R scores, 38% of the patients fell into the very-low-risk group, 33% into the low-risk group, 18% into the intermediate-risk group, 7% into the high-risk group, and 4% into the very-high-risk group, Dr. Voso and her colleagues said.
With a median follow-up of 2.8 years, the IPSS-R predicted leukemia-free survival (P less than .001) and overall survival (P less than .001), and it was superior to both the classic IPSS and the WPSS in its predictive ability (P less than .001), they wrote.
In a multivariate model that considered all three scoring systems plus a variety of potential confounders (age, lactate dehydrogenase concentration, ferritin concentration, performance status, transfusion dependency, and type of therapy), the IPSS-R score was an independent predictor.
When peers in the intermediate-risk group were used as the comparator, patients had better leukemia-free survival if they fell in the very-low-risk group (hazard ratio [HR], 0.26; P less than .001) or low-risk group (HR, 0.58; P = .02), and patients had poorer leukemia-free survival if they fell in the high-risk group (HR, 1.72; P = .08) or very-high-risk group (HR, 3.26; P = .004).
Similarly, patients had better overall survival if they were in the very-low-risk group (HR, 0.29; P less than .001) or low-risk group (HR, 0.59; P = .04), and patients had poorer overall survival if they were in the high-risk group (HR, 1.67; P = .10) or very-high-risk group (HR, 5.13; P less than .001).
Dr. Voso disclosed receiving honoraria from Celgene.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Major finding: Compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.
Data source: A retrospective cohort study among 380 patients with myelodysplastic syndromes.
Disclosures: Dr. Voso disclosed receiving honoraria from Celgene.