Abstract 1025 Background: Nilotinib is a more potent and more selective inhibitor of BCR-ABL in-v... more Abstract 1025 Background: Nilotinib is a more potent and more selective inhibitor of BCR-ABL in-vitro than imatinib. A randomized Phase III study was conducted comparing these two therapies in adult patients with newly diagnosed Philadelphia Chromosome positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase (CP). Aim: To evaluate whether baseline health-related quality of life (HRQL) or symptom scores were predictive of clinical outcome in this phase III trial. Methods: A total of 846 patients were randomized to receive nilotinib 300 mg BID (n=282), nilotinib 400 mg BID (n=281) or imatinib 400mg QD (n=283). For these analyses to evaluate the impact of baseline HRQL on clinical outcomes, the treatment arms were combined. HRQL was assessed using the Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu). The FACT-Leu consists of four general subscales measuring physical, social/family, emotional, and functional well-being and a 17-item leukemia-specific subscale (LeuS). The FACT-G score is the sum of the four general well-being subscales. The questionnaire was administered at baseline, and at 3, 12, and 24 months. Baseline FACT-G and LeuS scores were divided into three equal-sized groups (i.e., tertiles). Patients with high, mid, and low baseline scores were compared on several clinical outcomes: best molecular response by Month 24, best cytogenetic response by Month 24, treatment discontinuation, hospitalization, dose modification of any kind (interruption, increase, or reduction), grade 3 or 4 adverse events, and missed cytogenetic tests. Chi-square tests were used to compare these dichotomous and categorical outcomes between baseline HRQL groups. The relationship between baseline HRQL scores and Sokal Risk groups was evaluated using analysis of variance. Higher scores on the FACT-G and LeuS indicate better HRQL and less symptom burden. Results: Mean baseline FACT-G scores were 97.8, 85.0, and 66.3, and mean baseline LeuS scores were 61.6, 53.8, and 42.2, for the high/mid/low tertile groups, respectively. There was no significant association between best molecular response by Month 24 or cytogenetic response by Month 24 and baseline FACT-G scores (p=0.149 and p=0.094, respectively). There was an association between best molecular response by Month 24 and baseline LeuS scores (p=0.043) but no significant association with best cytogenetic response by Month 24 (p=0.316). There were no significant associations with either dose modifications (p=0.252 for FACT-G, p=0.643 for LeuS), grade 3 or 4 adverse events (p=0.531 for FACT-G, p=0.831 for LeuS), or missed cytogenetic tests (p=0.722 for FACT-G, p=0.374 for LeuS). There was a significant association between treatment discontinuation and baseline FACT-G scores (p=0.007). Only 18% of patients with the highest baseline FACT-G scores discontinued treatment compared to 26% in the middle group and 31% in the group with the lowest baseline FACT-G scores. This relationship was not statistically significant for baseline LeuS scores (p=0.070). Fourteen percent of patients with high baseline FACT-G scores were hospitalized at some point during the study, compared to 15% of patients with mid FACT-G scores, and 22% with low baseline FACT-G (p=0.099). However, 11% of patients with high LeuS scores were hospitalized compared to 20% of patients with mid-range LeuS scores, and 21% of patients with low LeuS scores (p=0.018). The mean baseline FACT-G scores were 81.4, 83.5, and 83.4 (p=0.288), and the mean baseline LeuS scores were 51.1, 53.4, and 52.5 (p=0.042), for patients with high, intermediate, and low Sokal scores, respectively. Conclusions: In patients with newly diagnosed CML-CP, worse general HRQL at baseline was predictive for treatment discontinuation, but not predictive for best molecular response. Leukemia related symptoms at baseline were associated with a greater likelihood of subsequent hospitalization and moderately associated with molecular response. Baseline HRQL was not clearly associated with Sokal scores. These findings suggest that among patients with newly diagnosed CML-CP, examination of baseline HRQL and symptoms may allow patients and clinicians to better anticipate outcomes such as hospitalizations and continuation of therapy. Disclosures: Beaumont: Novartis: Research Funding. Nowinski:Novartis: Research Funding. Coombs:Novartis: Employment, Equity Ownership. Szczudlo:Novartis: Employment, Equity Ownership. Blakesley:Novartis: Employment, Equity Ownership. Gallagher:Novartis: Employment, Equity Ownership. Burns:Novartis: Research Funding. Cella:Novartis: Research Funding.
Itch compromises quality of life, but most itch assessments focus only on itch intensity. We aime... more Itch compromises quality of life, but most itch assessments focus only on itch intensity. We aimed to develop and validate a comprehensive PROMIS (Patient Reported Outcomes Measurement Information System®) pediatric measure for itch symptoms and itch impact, defined as the effect specifically of itch on physical, mental, and social health, all of which can affect life quality. After literature review, concept elicitation and cognitive interviews with parents and children with itch, and repeated content-expert review, an item pool was generated and refined. The pool was calibrated with data from 499 pruritic children using exploratory and confirmatory factor analyses, item response theory, and item fit analysis. The resultant 45-item bank, PROMIS Itch Questionnaire - Child (PIQ-C), showed good convergent and discriminant validity in 181 children 8-17 years of age, discriminating children with different levels of severity, and was responsive to change. Strong correlations (rho>.60) were observed with pain and sleep measures, and moderate correlations with other pediatric PROMIS measures. PIQ-C comprehensively measures itch intensity and burden, providing an itch-specific alternative for assessing life quality. The independent calibration of each item/question allows for flexibility in generating short-forms or computerized adaptive testing for efficient use in research and office practice.
Patients with chronic myeloid leukemia (CML) in chronic phase are living longer on BCR-ABL1 tyros... more Patients with chronic myeloid leukemia (CML) in chronic phase are living longer on BCR-ABL1 tyrosine kinase inhibitor (TKI) therapy, placing emphasis on issues related to symptom burden and quality of life (QoL). Furthermore, the potential for adverse events with longer-term therapy may result in dose adjustments, treatment discontinuation, or nonadherence, all of which may negatively affect treatment efficacy and QoL. However, instruments to specifically measure the impact of symptom burden and treatment on health-related QoL in patients with CML have not been widely available until recently. The FACT-Leu is a validated tool that measures leukemia-specific and more general QoL concerns. Other tools specific to CML, including the MDASI-CML and the EORTC QLQ-CML24, are undergoing validation. Here, we describe TKI therapy-related symptom burden and its effect on adherence and treatment response, outline instruments to measure symptom burden and QoL in CML, and summarize the available clinical data on QoL of patients on TKI therapy. QoL is an aspect of CML disease management that will continue to gain prominence in the coming years. We believe that the instruments developed now will have a role in informing treatment decisions in routine practice and allowing clinicians to proactively address issues related to symptom burden and QoL.
Abstract 1025 Background: Nilotinib is a more potent and more selective inhibitor of BCR-ABL in-v... more Abstract 1025 Background: Nilotinib is a more potent and more selective inhibitor of BCR-ABL in-vitro than imatinib. A randomized Phase III study was conducted comparing these two therapies in adult patients with newly diagnosed Philadelphia Chromosome positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase (CP). Aim: To evaluate whether baseline health-related quality of life (HRQL) or symptom scores were predictive of clinical outcome in this phase III trial. Methods: A total of 846 patients were randomized to receive nilotinib 300 mg BID (n=282), nilotinib 400 mg BID (n=281) or imatinib 400mg QD (n=283). For these analyses to evaluate the impact of baseline HRQL on clinical outcomes, the treatment arms were combined. HRQL was assessed using the Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu). The FACT-Leu consists of four general subscales measuring physical, social/family, emotional, and functional well-being and a 17-item leukemia-specific subscale (LeuS). The FACT-G score is the sum of the four general well-being subscales. The questionnaire was administered at baseline, and at 3, 12, and 24 months. Baseline FACT-G and LeuS scores were divided into three equal-sized groups (i.e., tertiles). Patients with high, mid, and low baseline scores were compared on several clinical outcomes: best molecular response by Month 24, best cytogenetic response by Month 24, treatment discontinuation, hospitalization, dose modification of any kind (interruption, increase, or reduction), grade 3 or 4 adverse events, and missed cytogenetic tests. Chi-square tests were used to compare these dichotomous and categorical outcomes between baseline HRQL groups. The relationship between baseline HRQL scores and Sokal Risk groups was evaluated using analysis of variance. Higher scores on the FACT-G and LeuS indicate better HRQL and less symptom burden. Results: Mean baseline FACT-G scores were 97.8, 85.0, and 66.3, and mean baseline LeuS scores were 61.6, 53.8, and 42.2, for the high/mid/low tertile groups, respectively. There was no significant association between best molecular response by Month 24 or cytogenetic response by Month 24 and baseline FACT-G scores (p=0.149 and p=0.094, respectively). There was an association between best molecular response by Month 24 and baseline LeuS scores (p=0.043) but no significant association with best cytogenetic response by Month 24 (p=0.316). There were no significant associations with either dose modifications (p=0.252 for FACT-G, p=0.643 for LeuS), grade 3 or 4 adverse events (p=0.531 for FACT-G, p=0.831 for LeuS), or missed cytogenetic tests (p=0.722 for FACT-G, p=0.374 for LeuS). There was a significant association between treatment discontinuation and baseline FACT-G scores (p=0.007). Only 18% of patients with the highest baseline FACT-G scores discontinued treatment compared to 26% in the middle group and 31% in the group with the lowest baseline FACT-G scores. This relationship was not statistically significant for baseline LeuS scores (p=0.070). Fourteen percent of patients with high baseline FACT-G scores were hospitalized at some point during the study, compared to 15% of patients with mid FACT-G scores, and 22% with low baseline FACT-G (p=0.099). However, 11% of patients with high LeuS scores were hospitalized compared to 20% of patients with mid-range LeuS scores, and 21% of patients with low LeuS scores (p=0.018). The mean baseline FACT-G scores were 81.4, 83.5, and 83.4 (p=0.288), and the mean baseline LeuS scores were 51.1, 53.4, and 52.5 (p=0.042), for patients with high, intermediate, and low Sokal scores, respectively. Conclusions: In patients with newly diagnosed CML-CP, worse general HRQL at baseline was predictive for treatment discontinuation, but not predictive for best molecular response. Leukemia related symptoms at baseline were associated with a greater likelihood of subsequent hospitalization and moderately associated with molecular response. Baseline HRQL was not clearly associated with Sokal scores. These findings suggest that among patients with newly diagnosed CML-CP, examination of baseline HRQL and symptoms may allow patients and clinicians to better anticipate outcomes such as hospitalizations and continuation of therapy. Disclosures: Beaumont: Novartis: Research Funding. Nowinski:Novartis: Research Funding. Coombs:Novartis: Employment, Equity Ownership. Szczudlo:Novartis: Employment, Equity Ownership. Blakesley:Novartis: Employment, Equity Ownership. Gallagher:Novartis: Employment, Equity Ownership. Burns:Novartis: Research Funding. Cella:Novartis: Research Funding.
Itch compromises quality of life, but most itch assessments focus only on itch intensity. We aime... more Itch compromises quality of life, but most itch assessments focus only on itch intensity. We aimed to develop and validate a comprehensive PROMIS (Patient Reported Outcomes Measurement Information System®) pediatric measure for itch symptoms and itch impact, defined as the effect specifically of itch on physical, mental, and social health, all of which can affect life quality. After literature review, concept elicitation and cognitive interviews with parents and children with itch, and repeated content-expert review, an item pool was generated and refined. The pool was calibrated with data from 499 pruritic children using exploratory and confirmatory factor analyses, item response theory, and item fit analysis. The resultant 45-item bank, PROMIS Itch Questionnaire - Child (PIQ-C), showed good convergent and discriminant validity in 181 children 8-17 years of age, discriminating children with different levels of severity, and was responsive to change. Strong correlations (rho>.60) were observed with pain and sleep measures, and moderate correlations with other pediatric PROMIS measures. PIQ-C comprehensively measures itch intensity and burden, providing an itch-specific alternative for assessing life quality. The independent calibration of each item/question allows for flexibility in generating short-forms or computerized adaptive testing for efficient use in research and office practice.
Patients with chronic myeloid leukemia (CML) in chronic phase are living longer on BCR-ABL1 tyros... more Patients with chronic myeloid leukemia (CML) in chronic phase are living longer on BCR-ABL1 tyrosine kinase inhibitor (TKI) therapy, placing emphasis on issues related to symptom burden and quality of life (QoL). Furthermore, the potential for adverse events with longer-term therapy may result in dose adjustments, treatment discontinuation, or nonadherence, all of which may negatively affect treatment efficacy and QoL. However, instruments to specifically measure the impact of symptom burden and treatment on health-related QoL in patients with CML have not been widely available until recently. The FACT-Leu is a validated tool that measures leukemia-specific and more general QoL concerns. Other tools specific to CML, including the MDASI-CML and the EORTC QLQ-CML24, are undergoing validation. Here, we describe TKI therapy-related symptom burden and its effect on adherence and treatment response, outline instruments to measure symptom burden and QoL in CML, and summarize the available clinical data on QoL of patients on TKI therapy. QoL is an aspect of CML disease management that will continue to gain prominence in the coming years. We believe that the instruments developed now will have a role in informing treatment decisions in routine practice and allowing clinicians to proactively address issues related to symptom burden and QoL.
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Papers by Cindy Nowinski