ALBERT

Description: Introduction Due to recent changes in acute leukemia treatment, there is an urgent need for greater understanding of the factors affecting quality of life at different points in the journey of patients. The Acute Leukemia Advocates Network (ALAN) is running a multi-country survey to gather information on the experiences, quality of life and symptoms of adults (16+) with different types of acute leukemia. The study objectives were to: (1) investigate whether the HM-PRO scores differ according to disease state; (2) determine whether those with worse scores on Q13-Q18 (patient-reported experience) will also report higher HM-PRO scores (a worse quality of life); (3) examine if there are significant differences for the HM-PRO scores between acute leukemia types and gender. Methods This survey comprises 99 items and was designed based on a literature review of quality of life and acute leukemia followed by input from clinical and patient advocacy experts. HM-PRO, an instrument to measure patient-reported outcomes in patients with hematological malignancies, was incorporated into the survey for assessing quality of life and symptoms. This is a composite measure consisting of: Part A (impact/quality of life); and Part B (signs and symptoms). A higher score in each part represents more impaired outcomes. Question 9 provides a measure for disease state (undergoing treatment, in remission following treatment or relapsed following treatment). We hypothesised that patients with a worse experience in each of the following areas would report a worse overall quality of life: physical symptoms and side effects (Q13), emotional impact (Q14), physical and mental health (Q15), information from healthcare professionals (Q16), ability to perform meaningful activities (Q17) and well-being of carers, friends and family (Q18). These are itemised on an interval scale ranging from 0-10, where 0 represents a bad experience and 10, a good experience. Questions 19-99 investigated further each of the hypotheses, to identify patient issues and background demographic questions. The survey was translated into 9 languages and promoted via patient advocacy groups from 1/3/19 to 31/5/19 (ongoing). Spearman correlation analysis was used to determine the direction and strength of relationships between the measures. Two sample Wilcoxon rank-sum tests and Kruskal-Wallis rank test were applied to test for differences between groups. Results There were 371 respondents: acute myeloid leukemia (213), acute lymphoblastic leukemia (86) and acute promyelocytic leukemia (72). There was no evidence of any difference in the HM-PRO score for either Part A - quality of life (p=0.9) or Part B - signs and symptoms (p=0.4) between acute leukemia types. Of these 149 were men and 219 female and 3 provided no gender. The median Part A score for males and females was 24.1 and 30.39, respectively (p=0.07). The median for Part B was 17.6 and 23.5 for males and females, respectively (p=0.01) with females reporting greater burden of signs and symptoms. The analysis suggests that there is a difference in the HM-PRO scores between disease state, with those in remission following treatment having lower HM-PRO scores (better quality of life) than those currently undergoing treatment (Figure 1&2). The results confirmed our hypotheses that those with worse scores for Q13-Q18 have a worse quality of life (higher HM-PRO score). The responses to all of these questions were either weakly or moderately related to scores of both parts of the HM-PRO (Table 1). The correlations (negative) were all statistically significant, suggesting that low HM-PRO scores are associated with good experiences and vice versa. Some individual questions were also highly correlated (rs = ≥0.7) with one another (e.g. Q14 and Q13, or Q17 and Q18), showing internal stability of the items. Conclusion The study confirms that acute leukemia patients in remission report a better quality of life than those currently undergoing treatment. However, there is no evidence of any difference in the HM-PRO scores between acute leukemia types which needs to be further explored in controlled studies. In terms of gender differences, the results indicate that female patients experience greater impact on quality of life and symptoms. Furthermore, patients with worse reported experience (Q13-18) have a lower overall quality of life, suggesting that improving support in these areas may enhance overall quality of life. Disclosures Pemberton-Whiteley: CML Advocates Network: Membership on an entity's Board of Directors or advisory committees; Patient Evidence: Equity Ownership; AbbVie: Other: Grant funding; Amgen: Consultancy, Other: Grant funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Other: Grant funding, Speakers Bureau; Celgene: Consultancy, Other: Grant funding; Acute Leukemia Advocates Network (ALAN): Consultancy; Pfizer: Consultancy, Other: Grant Funding, Speakers Bureau; Takeda: Other: Grant funding; Shire: Other: Grant Funding; Kyowa Kirin: Other: Grant funding; Novartis: Consultancy, Other: Grant funding, Speakers Bureau; Incyte: Consultancy, Other: Grant funding; Jazz: Other: Grant funding, Speakers Bureau; Janssen: Consultancy, Other: Grant funding; Daiichi Sankyo: Other: Grant funding; Gilead: Other: Grant funding, Speakers Bureau; Leukaemia Care: Employment. Oliva:Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Apellis: Consultancy. Geissler:Incyte: Research Funding; Roche: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; UCB: Consultancy, Speakers Bureau; Servier: Consultancy; Takeda: Research Funding; Pfizer: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau. Wintrich:Takeda: Consultancy; Janssen: Other: Grant Funding; Celgene: Other: Grant Funding; Novartis: Consultancy, Other: Grant Funding. Salek:Pfizer: Honoraria, Speakers Bureau; Merck: Consultancy; Agios Pharmaceuticals, Inc.: Consultancy, Honoraria. Ionova:Takeda, BMS: Other: Principal Investigator of IISR, Research Funding. Tate:Quality Health: Employment. Bradley:Quality Health: Employment.

Description: Background Adherence to the prescribed dose of tyrosine kinase inhibitors (TKIs) is critical to maximize treatment effectiveness in chronic myeloid leukemia (CML). While patient-centered outcome studies are lacking in this area, literature has shown that a significant proportion of patients report both intentional and unintentional non-adherence. Objective The main objective of this multivariate analysis was to identify risk factors that might predict intentional non-adherence to TKIs in CML. Methods The CML Advocates Network, connecting 79 CML patient groups from 63 countries, conducted an international project investigating patterns of medication-taking behaviors of CML patients, supported by CML investigator groups in Germany, Italy and France. We sought to demonstrate the relationship between 16 factors and adherence in this multinational cohort. A web-based survey was launched in 12 languages, enrolling CML patients from Sept 2012 to Jan 2013. The identical questionnaire was provided to a cohort of patients recruited in clinics in France, Germany and Italy, returned by patients in a pre-stamped envelope to an independent data center. Questions included potential factors associated with non-adherence as well as on patients' perception of disease and treatment burden. Based on previous literature and on clinical relevance, a pool of 16 candidate factors, potentially predicting intentional non-adherence, was selected for analysis. These included: frequency of CML medication, co-payment for CML treatment, and current TKI therapy. Patients who reported having skipped intentionally one or more doses over the last year were considered as “intentional non-adherers”. Univariate logistic regression analysis was performed to examine the impact of pre-selected candidate factors on the probability of intentional non-adherence. Two multivariate models were fitted based on line of therapy received by patients (i.e. first line and second or greater lines of therapy). Results This patient-led study is the largest study conducted to date on the influencers of non-adherence in CML. Overall, 2546 adult CML patients (47.6% female) under TKI treatment from 79 countries responded to the survey. 2151 patients responded online, 395 questionnaires were returned on paper. No significant difference on intentional non-adherence was observed between paper or online responses. Median age of patients was 51 years (range 18-96) and median time from diagnosis was 4 years (0-27). Overall, 51.6% of all respondents reported having missed at least one dose unintentionally over the last year, and 19.5% did so intentionally. This analysis regards the intentional non-adherent population (n=490). Of those, 60% were on imatinib, 20% on nilotinib, 14% on dasatinib, 6% on other TKIs. Several factors predicted intentional non-adherence in univariate analysis, including education level (P=0.016) and co-payment for TKIs (P=0.005). For patients on first line TKI (n=1551), the following factors independently predicted a higher likelihood of being intentional non-adherers: younger age (P=0.015), longer time since diagnosis (P

Description: Background: In patients with chronic myeloid leukemia in chronic phase (CML-CP), the efficacy of ATP-competitive tyrosine kinase inhibitors (TKIs) has resulted in treatment-free remission (TFR) as a primary treatment goal for those with a sustained deep molecular response (DMR). However, most patients treated with imatinib fail to achieve a sustained DMR, meaning that they cannot benefit from TFR. Asciminib is a potent and specific inhibitor of BCR-ABL1. Unlike BCR-ABL1 TKIs that target the ATP binding site, asciminib binds to the myristate pocket of ABL1. Preclinical data showed that the combination of asciminib with ATP-competitive TKIs may provide more potent BCR-ABL1 inhibition and prevent emergence of resistance mutations (Wylie et al. Nature. 2017;543:733-737). In an ongoing phase 1 study (NCT02081378), asciminib demonstrated clinical activity and was well tolerated as a single agent (Hughes et al. Blood. 2016;128 [abstract 625]). In the same study, asciminib in combination with imatinib showed promising preliminary efficacy and a good safety profile in patients resistant/intolerant of ≥2 prior TKIs (Cortes et al. HemaSphere. 2019;3(S1) [abstract S388]). These findings informed the dose of asciminib to be further evaluated in combination with imatinib. An ongoing phase 3 study (NCT03106779) is evaluating asciminib vs bosutinib in patients previously treated with ≥2 ATP-binding site TKIs (Mauro et al. J Clin Oncol. 2019;37 [abstract TPS7070]). Here, we describe the ASCiminib add-on 4-arm study evaluating MOlecular REsponse (ASC4MORE) in patients. This is a phase 2 study evaluating the efficacy of adding asciminib to ongoing imatinib therapy in patients with CML-CP who have not achieved DMR with long-term frontline imatinib (CABL001E2201; NCT03578367). Methods: Study participants are aged ≥18 years, have CML-CP, and have been treated with frontline imatinib for ≥12 months. Study entry requires patients to be receiving imatinib 400 mg once daily (QD) at randomization, have BCR-ABL1 transcript levels in the range of ≤1% to 〉0.01% on the International Scale (IS), no prior achievement of MR4 (BCR-ABL1IS ≤0.01%) confirmed by two consecutive tests, and no prior treatment failure. Overall, ~80 patients will be randomized 1:1:1:1 to one of four arms (Figure): either asciminib 40 mg QD or 60 mg QD added to imatinib 400 mg QD; continued treatment with imatinib 400 mg QD; or switch to nilotinib 300 mg twice daily. Study treatment will continue until treatment resistance or intolerance, or up to 96 weeks after the last randomized patient has begun treatment. The primary objective of this study is to assess whether asciminib add-on to imatinib is more effective than imatinib continuation; the primary endpoint is the rate of MR4.5 (BCR-ABL1IS ≤0.0032%) at 48 weeks. Secondary objectives include: to estimate the efficacy of switch to nilotinib; to estimate the difference in efficacy between asciminib add-on to imatinib and switch to nilotinib; and to characterize the safety of asciminib add-on to imatinib. Exploratory objectives include TFR eligibility at the end of the study and patient-reported outcomes. Patients in the imatinib continuation arm who have not achieved MR4.5 at 48 weeks may cross over to receive add-on asciminib. This study is ongoing, with 23 patients randomized as of 22 July 2019. Disclosures Saglio: BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy; Incyte: Consultancy; Pfizer: Consultancy; Jansen: Consultancy; Celgene: Consultancy. Hughes:Novartis, Bristol-Myers Squibb, Celgene: Research Funding; Novartis, Bristol-Myers Squibb: Consultancy, Other: Travel. Geissler:Novartis: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy; Amgen: Consultancy; Incyte: Research Funding; Takeda: Research Funding; Biomarin: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; UCB: Consultancy, Speakers Bureau; Servier: Consultancy. Kapoor:Novartis: Employment. Longin:Novartis: Employment. Mukherjee:Novartis: Employment. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; BiolineRx: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Biopath Holdings: Consultancy, Honoraria; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

Description: Background In Chronic Myeloid Leukemia (CML), Treatment-free Remission (TFR) refers to having a stable deep molecular response without the need for ongoing Tyrosine Kinase Inhibitor (TKI) treatment. While first recommendations exist about how to manage stopping and re-starting therapy, based on data from the EURO-SKI study, much is still unknown about the experiences of those considering and undertaking TFR. Through this study, we sought to obtain quantitative evidence of patient experience that has previously only been anecdotal and to identify areas of unmet needs. One strong theme to emerge was patients' differing views on the need for psychological support. Method A global online survey was conducted, recruiting patients through CML patient associations, via online forums, social media and other methods. The questionnaire was designed by an expert panel of eight CML patients to capture the experiences of people along all phases of the TFR journey. The different phases were classified as: Phase I - Considerations around stopping treatment; Phase II - Probation period (experiences during the first 6 months of stopping treatment); Phase IIIA -Restarting treatment (experiences where treatment had to restart due to molecular reoccurrence), and Phase IIIB - Long-term remission (experiences of being in long-term, treatment-free remission). Once the question set was agreed, the questionnaire went through two rounds of testing by eight volunteers. This exercise contributed towards refining the questionnaire into a finished version. The questionnaire was translated into eleven languages: Arabic, Danish, English, Finnish, French, German, Hebrew, Italian, Japanese, Russian and Spanish. Fieldwork lasted 20 weeks. Results A total of 1016 responses were collected from CML patients across 68 countries. Patients only answered the sections of the questionnaire that were relevant for them. All 1016 had experience of Phase I, 494 (49%) had experience of Phase II, 159 (16%) had experience of Phase IIIA, and 203 (20%) had experience of IIIB. Of the 494 patients who stopped treatment, 32% said disease reoccurred and 41% reported being in long-term remission (this includes

Description: Background The Acute Leukemia Advocates Network (ALAN) conducted a multi-country survey to gather information on the experiences, quality of life (QoL) and symptoms of adults (16+) with acute leukemia [acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and acute promyelocytic leukemia (APL)]. Aims To examine which factors are most associated with differences in QoL and symptom burden (measured by HM-PRO scores), focusing here on age and patient-reported experience. Methods This survey comprised 99 items, designed from a literature review of QoL and acute leukemia followed by input from clinical and patient advocacy experts. The study material was translated (9 languages) and promoted via patient advocacy groups from March 1, 2019 to November 29, 2019. HM-PRO, an instrument designed to measure patient-reported outcomes in patients with hematological malignancies, was incorporated into the study for assessing QoL and symptoms. This consists of: Part A (impact/QoL); and Part B (signs and symptoms). A higher score in each part represents greater (negative) impact on QoL and symptom burden. Q6 of the survey asked respondents to report their year of birth. Q9 of the survey provides a measure for disease state: undergoing treatment, in remission following treatment or relapsed following treatment. It was hypothesised that patients with a worse experience in each of the following areas would report a worse overall QoL: management by healthcare professional of physical symptoms and side effects (Q13) and emotional impact (Q14); physical and mental health (Q15), information from healthcare professionals (Q16), ability to perform meaningful activities (Q17) and well-being of carers, friends and family (Q18). Spearman correlation analysis was used to determine the direction and strength of relationships between the measures. Wilcoxon rank-sum, Chi-squared and Kruskal-Wallis rank test were used to examine the differences between groups. Multivariable linear regression, with interaction terms was used to investigate the relationships between the questions and the tumour groups. Results There were 552 respondents. Patients self-reported their acute leukemia diagnosis - 332 AML, 139 ALL and 81 APL. There was no overall significant difference between Part A (p=0.55) and Part B (0.23) HM-PRO scores for different acute leukemia types. Of these, 158 were aged 16-40, 240 were 41-60, 150 were 61-87 and 4 did not answer this question. The results suggest a significant difference across the age groups in both Part A (p=0.005) and Part B (p=0.03) of the HM-PRO scores and signs and symptoms in with younger patients reporting a worse QoL. The results also confirmed our hypothesis that those with worse scores for Q13-Q18 have a worse QoL (higher HM-PRO score). The correlations (negative) were all statistically significant (p 〈 0.05), suggesting that good experiences are associated with low HM-PRO scores and vice versa (Table 1). The predictive value of Q17 and Q18 on overall QoL (HM-PRO scores) varied by tumour type, with a weaker relationship shown for the ALL group. This was confirmed as significant by the multivariable analysis. Q13-Q16 factors mostly appeared to have similar strengths of relationship with the QoL scores between the different acute leukemia types. Responses to Q14 differed significantly between disease types (p=0.01) with median 6 for APL vs 7 for ALL and 8 for AML. Similar differences were observed for Q13. Conclusions The results confirm there are significant differences (as measured by HM-PRO) in both Part A (impact/QoL) and Part B (signs and symptoms) across age groups, with younger acute leukemia patients reporting a worse QoL. Patients with worse reported experience (Q13-18) have worse HM-PRO scores, suggesting that improving support in these areas may enhance overall QoL. Disclosures Pemberton-Whiteley: Celgene: Consultancy, Other; Leukaemia Care: Current Employment; Acute Leukemia Advocates Network: Consultancy, Membership on an entity's Board of Directors or advisory committees; CML Advocates Network: Membership on an entity's Board of Directors or advisory committees; Blood Cancer Alliance: Membership on an entity's Board of Directors or advisory committees; WECAN (Workgroup of European Cancer Patient Advocacy Networks): Consultancy, Membership on an entity's Board of Directors or advisory committees; European Cancer Organisation - Patient Advisory Committee: Membership on an entity's Board of Directors or advisory committees; Patient Evidence: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Other: Organisational Grant Funding; Agios: Other: Organisational Grant Funding; Amgen: Consultancy, Other: Organisational Grant Funding; Astellas: Other; Bristol-Myers Squibb: Consultancy, Other, Speakers Bureau; Daiichi Sankyo: Other; Gilead: Other; Incyte: Consultancy, Other; Jazz: Other, Speakers Bureau; Janssen: Consultancy, Other; Kyowa Kirin: Other; Novartis: Consultancy, Other, Speakers Bureau; Pfizer: Consultancy, Other, Speakers Bureau; Servier: Consultancy, Other; Takeda: Other. Nier:Acute Leukemia Advocates Network: Consultancy; Servier: Consultancy. Geissler:BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding, Speakers Bureau; Incyte: Research Funding; Takeda: Research Funding; Gilead: Consultancy, Speakers Bureau; Biomarin: Consultancy; Janssen: Consultancy, Speakers Bureau; Roche: Consultancy; Servier: Consultancy; UCB: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Wintrich:Takeda: Consultancy, Other: Project funding in MDS; Incyte: Consultancy, Other: Project funding in MDS; Novartis: Consultancy, Other: Project funding in MDS; Janssen: Consultancy, Other: Project funding in MDS; Celgene: Consultancy, Other: Project funding in MDS; Silence Therapeutics: Consultancy, Other: Project funding in MDS. Verhoeven:Novartis: Consultancy; Janssen: Consultancy. Christensen:Autisme 4700 DK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: Organisational Grant Funding; Bristol Myers Squib: Consultancy; Gilead: Other: Organisational Grant Funding; Incyte: Consultancy, Other: Organisational Grant Funding; Janssen: Consultancy, Other: Organisational Grant Funding; Novartis Nordic: Consultancy, Other: Organisational Grant Funding; Pfizer: Other: Organisational Grant Funding; Roche: Consultancy, Other: Organisational Grant Funding; Takeda: Consultancy, Other; LYLE: Consultancy, Membership on an entity's Board of Directors or advisory committees. Salek:Merck: Consultancy; Agios: Consultancy, Honoraria; Pfizer: Honoraria, Speakers Bureau. Oliva:Amgen: Consultancy; Abbvie: Consultancy; Apellis: Consultancy; Alexion: Consultancy; Novartis: Consultancy; BMS: Consultancy, Honoraria, Patents & Royalties, Speakers Bureau. Ionova:Takeda: Research Funding; BMS: Research Funding. Bradley:Quality Health Ltd: Current Employment. Tate:Quality Health Ltd: Current Employment.