SYMPTOMS, RISK CLASSIFICATION, AND SPLEEN SIZE IN JAK2 INHIBITOR-NAÏVE MYELOFIBROSIS: IMPLICATIONS FOR JAK2 INHIBITOR TREATMENT
(Abstract release date: 05/19/16)
EHA Library. Scheber R. 06/09/16; 132894; E1345
Dr. Robyn Scheber
Contributions
Contributions
Abstract
Abstract: E1345
Type: Eposter Presentation
Background
Symptom burden in myelofibrosis (MF) is severe and a risk factor for mortality (Blood 2010;115(9):1703-8). In trials comparing JAK2 treatment to best available therapy, patients receiving JAK2 therapy had significant alleviation in disease related symptom burden and decreased spleen size (N Engl J Med 2012;366:787-798).
Aims
To date no studies have evaluated which cutoffs are most associated with Dynamic International Prognostic Scoring System (DIPSS) risk score and thus may identify patients for further symptom-directed treatment.
Methods
Patient demographics, symptom burden, DIPSS risk classification, and spleen size were collected from MF patients at an office visit. Symptoms were assessed via the MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103). The TSS was calculated as the summated 10-item score, reported in a range of 0-100 for patients completing at least 6/10 symptom items. Associations of symptoms (worst single symptom score and TSS utilizing various cutoffs) with DIPSS risk and spleen size (categorized as >10cm and separately as >15cm) were investigated using ANOVA F-tests and ordinal logistic regression. Lowest Akaike Information Criteria (AIC) was used to select an optimal model among all a priori models.
Results
Demographics and symptom burden: 851 MF patients with known DIPSS risk score or spleen size were selected, of which 695 were JAK2 inhibitor-naïve (420 with DIPSS risk, 425 with known spleen size). Among participants, 58% had a TSS >20. The worst single symptom (or multiple worst if tied) was most often fatigue (50%) followed by night sweats (19%) and satiety (19%). The worst single symptom score was >5 for 57% patients, and 50% had both a TSS >20 and worst single symptom score >5. Associations of symptoms with DIPSS risk and spleen size: Similar to prior published data, increased TSS was significantly associated with higher DIPSS risk score (p<0.001) with mean TSS of 15.8, 24.5, 30.1, and 37.7 for low, int-1, int-2, and high risk groups, respectively. Increased TSS was also significantly associated with spleen size (>10cm: mean TSS 25.2 vs 30.0, p=0.02; >15cm: 25.5 vs 32.9, p=0.004). Increased worst single symptom severity was associated with higher DIPSS risk score (mean worst single symptom score 5.0 vs 6.3 vs 7.0 vs 7.5, p<0.001) as well as the largest spleen size (>10cm: 6.3 vs 6.8, p=0.11; >15cm: 6.3 vs 7.3, p=0.02). Ordinal logistic regression modeling of DIPSS risk: When comparing models, worst single symptom score >5 had the lowest AIC (Table 1), suggesting this as an optimal model predicting increased risk. In this model, worst single symptom score >5 was associated with 14.1%, 49.3%, 32.3%, and 4.3% probabilities of being low, int-1, int-2, and high risk, compared to 20.8%, 52.8%, 23.7%, and 2.7% for single score ≤5. The next best model was based on a TSS score >20 alone (AIC 936.657). Among combined TSS and single item models, a combined TSS >20 and single item >5 had the relative lowest AIC (938.51).
Conclusion
Alleviation of MPN symptoms, now measurable through standardized instruments such as the TSS, are an integral part of assessing therapeutic impact in both clinical practice and trials. In our modeling, a cutoff criteria of the worst single symptom being >5/10 is optimal for predicting increased DIPSS risk score suggesting that this criterion may differentiate between which patients will most benefit from symptom-based treatment. We propose that JAK2 inhibitor treatment be strongly considered in any JAK2-inhibitor naïve MF patient with an individual symptom score >5.
Session topic: E-poster
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Quality of life
Type: Eposter Presentation
Background
Symptom burden in myelofibrosis (MF) is severe and a risk factor for mortality (Blood 2010;115(9):1703-8). In trials comparing JAK2 treatment to best available therapy, patients receiving JAK2 therapy had significant alleviation in disease related symptom burden and decreased spleen size (N Engl J Med 2012;366:787-798).
Aims
To date no studies have evaluated which cutoffs are most associated with Dynamic International Prognostic Scoring System (DIPSS) risk score and thus may identify patients for further symptom-directed treatment.
Methods
Patient demographics, symptom burden, DIPSS risk classification, and spleen size were collected from MF patients at an office visit. Symptoms were assessed via the MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103). The TSS was calculated as the summated 10-item score, reported in a range of 0-100 for patients completing at least 6/10 symptom items. Associations of symptoms (worst single symptom score and TSS utilizing various cutoffs) with DIPSS risk and spleen size (categorized as >10cm and separately as >15cm) were investigated using ANOVA F-tests and ordinal logistic regression. Lowest Akaike Information Criteria (AIC) was used to select an optimal model among all a priori models.
Results
Demographics and symptom burden: 851 MF patients with known DIPSS risk score or spleen size were selected, of which 695 were JAK2 inhibitor-naïve (420 with DIPSS risk, 425 with known spleen size). Among participants, 58% had a TSS >20. The worst single symptom (or multiple worst if tied) was most often fatigue (50%) followed by night sweats (19%) and satiety (19%). The worst single symptom score was >5 for 57% patients, and 50% had both a TSS >20 and worst single symptom score >5. Associations of symptoms with DIPSS risk and spleen size: Similar to prior published data, increased TSS was significantly associated with higher DIPSS risk score (p<0.001) with mean TSS of 15.8, 24.5, 30.1, and 37.7 for low, int-1, int-2, and high risk groups, respectively. Increased TSS was also significantly associated with spleen size (>10cm: mean TSS 25.2 vs 30.0, p=0.02; >15cm: 25.5 vs 32.9, p=0.004). Increased worst single symptom severity was associated with higher DIPSS risk score (mean worst single symptom score 5.0 vs 6.3 vs 7.0 vs 7.5, p<0.001) as well as the largest spleen size (>10cm: 6.3 vs 6.8, p=0.11; >15cm: 6.3 vs 7.3, p=0.02). Ordinal logistic regression modeling of DIPSS risk: When comparing models, worst single symptom score >5 had the lowest AIC (Table 1), suggesting this as an optimal model predicting increased risk. In this model, worst single symptom score >5 was associated with 14.1%, 49.3%, 32.3%, and 4.3% probabilities of being low, int-1, int-2, and high risk, compared to 20.8%, 52.8%, 23.7%, and 2.7% for single score ≤5. The next best model was based on a TSS score >20 alone (AIC 936.657). Among combined TSS and single item models, a combined TSS >20 and single item >5 had the relative lowest AIC (938.51).
Conclusion
Alleviation of MPN symptoms, now measurable through standardized instruments such as the TSS, are an integral part of assessing therapeutic impact in both clinical practice and trials. In our modeling, a cutoff criteria of the worst single symptom being >5/10 is optimal for predicting increased DIPSS risk score suggesting that this criterion may differentiate between which patients will most benefit from symptom-based treatment. We propose that JAK2 inhibitor treatment be strongly considered in any JAK2-inhibitor naïve MF patient with an individual symptom score >5.
Session topic: E-poster
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Quality of life
Abstract: E1345
Type: Eposter Presentation
Background
Symptom burden in myelofibrosis (MF) is severe and a risk factor for mortality (Blood 2010;115(9):1703-8). In trials comparing JAK2 treatment to best available therapy, patients receiving JAK2 therapy had significant alleviation in disease related symptom burden and decreased spleen size (N Engl J Med 2012;366:787-798).
Aims
To date no studies have evaluated which cutoffs are most associated with Dynamic International Prognostic Scoring System (DIPSS) risk score and thus may identify patients for further symptom-directed treatment.
Methods
Patient demographics, symptom burden, DIPSS risk classification, and spleen size were collected from MF patients at an office visit. Symptoms were assessed via the MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103). The TSS was calculated as the summated 10-item score, reported in a range of 0-100 for patients completing at least 6/10 symptom items. Associations of symptoms (worst single symptom score and TSS utilizing various cutoffs) with DIPSS risk and spleen size (categorized as >10cm and separately as >15cm) were investigated using ANOVA F-tests and ordinal logistic regression. Lowest Akaike Information Criteria (AIC) was used to select an optimal model among all a priori models.
Results
Demographics and symptom burden: 851 MF patients with known DIPSS risk score or spleen size were selected, of which 695 were JAK2 inhibitor-naïve (420 with DIPSS risk, 425 with known spleen size). Among participants, 58% had a TSS >20. The worst single symptom (or multiple worst if tied) was most often fatigue (50%) followed by night sweats (19%) and satiety (19%). The worst single symptom score was >5 for 57% patients, and 50% had both a TSS >20 and worst single symptom score >5. Associations of symptoms with DIPSS risk and spleen size: Similar to prior published data, increased TSS was significantly associated with higher DIPSS risk score (p<0.001) with mean TSS of 15.8, 24.5, 30.1, and 37.7 for low, int-1, int-2, and high risk groups, respectively. Increased TSS was also significantly associated with spleen size (>10cm: mean TSS 25.2 vs 30.0, p=0.02; >15cm: 25.5 vs 32.9, p=0.004). Increased worst single symptom severity was associated with higher DIPSS risk score (mean worst single symptom score 5.0 vs 6.3 vs 7.0 vs 7.5, p<0.001) as well as the largest spleen size (>10cm: 6.3 vs 6.8, p=0.11; >15cm: 6.3 vs 7.3, p=0.02). Ordinal logistic regression modeling of DIPSS risk: When comparing models, worst single symptom score >5 had the lowest AIC (Table 1), suggesting this as an optimal model predicting increased risk. In this model, worst single symptom score >5 was associated with 14.1%, 49.3%, 32.3%, and 4.3% probabilities of being low, int-1, int-2, and high risk, compared to 20.8%, 52.8%, 23.7%, and 2.7% for single score ≤5. The next best model was based on a TSS score >20 alone (AIC 936.657). Among combined TSS and single item models, a combined TSS >20 and single item >5 had the relative lowest AIC (938.51).
Conclusion
Alleviation of MPN symptoms, now measurable through standardized instruments such as the TSS, are an integral part of assessing therapeutic impact in both clinical practice and trials. In our modeling, a cutoff criteria of the worst single symptom being >5/10 is optimal for predicting increased DIPSS risk score suggesting that this criterion may differentiate between which patients will most benefit from symptom-based treatment. We propose that JAK2 inhibitor treatment be strongly considered in any JAK2-inhibitor naïve MF patient with an individual symptom score >5.
Session topic: E-poster
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Quality of life
Type: Eposter Presentation
Background
Symptom burden in myelofibrosis (MF) is severe and a risk factor for mortality (Blood 2010;115(9):1703-8). In trials comparing JAK2 treatment to best available therapy, patients receiving JAK2 therapy had significant alleviation in disease related symptom burden and decreased spleen size (N Engl J Med 2012;366:787-798).
Aims
To date no studies have evaluated which cutoffs are most associated with Dynamic International Prognostic Scoring System (DIPSS) risk score and thus may identify patients for further symptom-directed treatment.
Methods
Patient demographics, symptom burden, DIPSS risk classification, and spleen size were collected from MF patients at an office visit. Symptoms were assessed via the MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103). The TSS was calculated as the summated 10-item score, reported in a range of 0-100 for patients completing at least 6/10 symptom items. Associations of symptoms (worst single symptom score and TSS utilizing various cutoffs) with DIPSS risk and spleen size (categorized as >10cm and separately as >15cm) were investigated using ANOVA F-tests and ordinal logistic regression. Lowest Akaike Information Criteria (AIC) was used to select an optimal model among all a priori models.
Results
Demographics and symptom burden: 851 MF patients with known DIPSS risk score or spleen size were selected, of which 695 were JAK2 inhibitor-naïve (420 with DIPSS risk, 425 with known spleen size). Among participants, 58% had a TSS >20. The worst single symptom (or multiple worst if tied) was most often fatigue (50%) followed by night sweats (19%) and satiety (19%). The worst single symptom score was >5 for 57% patients, and 50% had both a TSS >20 and worst single symptom score >5. Associations of symptoms with DIPSS risk and spleen size: Similar to prior published data, increased TSS was significantly associated with higher DIPSS risk score (p<0.001) with mean TSS of 15.8, 24.5, 30.1, and 37.7 for low, int-1, int-2, and high risk groups, respectively. Increased TSS was also significantly associated with spleen size (>10cm: mean TSS 25.2 vs 30.0, p=0.02; >15cm: 25.5 vs 32.9, p=0.004). Increased worst single symptom severity was associated with higher DIPSS risk score (mean worst single symptom score 5.0 vs 6.3 vs 7.0 vs 7.5, p<0.001) as well as the largest spleen size (>10cm: 6.3 vs 6.8, p=0.11; >15cm: 6.3 vs 7.3, p=0.02). Ordinal logistic regression modeling of DIPSS risk: When comparing models, worst single symptom score >5 had the lowest AIC (Table 1), suggesting this as an optimal model predicting increased risk. In this model, worst single symptom score >5 was associated with 14.1%, 49.3%, 32.3%, and 4.3% probabilities of being low, int-1, int-2, and high risk, compared to 20.8%, 52.8%, 23.7%, and 2.7% for single score ≤5. The next best model was based on a TSS score >20 alone (AIC 936.657). Among combined TSS and single item models, a combined TSS >20 and single item >5 had the relative lowest AIC (938.51).
Conclusion
Alleviation of MPN symptoms, now measurable through standardized instruments such as the TSS, are an integral part of assessing therapeutic impact in both clinical practice and trials. In our modeling, a cutoff criteria of the worst single symptom being >5/10 is optimal for predicting increased DIPSS risk score suggesting that this criterion may differentiate between which patients will most benefit from symptom-based treatment. We propose that JAK2 inhibitor treatment be strongly considered in any JAK2-inhibitor naïve MF patient with an individual symptom score >5.
Session topic: E-poster
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Quality of life
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