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Asciminib is the first BCR::ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP). Asciminib has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase without the T315I mutation who have received ≥2 prior tyrosine kinase inhibitors (TKIs) in phase I and III clinical trials and in patients with the T315I mutation who have received ≥1 prior TKI in phase I. ASC4FIRST (NCT04971226) is a phase III, multicenter, open-label, randomized study of asciminib versus investigator-selected TKI in patients with newly diagnosed chronic myeloid leukemia in chronic phase. The primary end point is major molecular response at week 48. Secondary end points include responses at and by scheduled time points, safety, pharmacokinetics and patient-reported outcomes. Clinical Trial Registration: NCT04971226 ( ClinicalTrials.gov ).

Treatment-free remission (TFR) after discontinuation of tyrosine kinase inhibitor therapy is now an emerging treatment goal for patients with chronic myeloid leukemia, who have achieved a deep and stable response to treatment. Although guidance is now available, patients' questions regarding this progressive concept have yet to be addressed. The overall aim of this European Steering Group is a patient-centered approach that educates patients on their treatment options, including TFR, facilitates better patient-physician relationships, and meets patients' emotional and psychological needs. The present report outlines 5 key topic areas on discontinuing tyrosine kinase therapy and the implications of TFR for patient-physician consideration: what TFR is; when TFR is appropriate; which patients might and might not be eligible for TFR; and patients' considerations for discontinuing therapy, such as tyrosine kinase withdrawal syndrome, potential psychological implications, molecular recurrence, and repeat treatment. This Steering Group advocates that patients with chronic myeloid leukemia should have access to high-quality, frequent molecular monitoring and be treated in a specialist center with appropriate medical and psychological support. As patient concerns with attempting TFR become forefront in patient-physician discussions, a greater number of eligible patients might be willing to discontinue therapy.

BACKGROUND: Patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) may be treated with 1 of the 4 tyrosine kinase inhibitors (TKIs) approved for first-line (1L) use: the first-generation TKI imatinib and the second-generation (2G) TKIs bosutinib, dasatinib, and nilotinib. Deep molecular responses (DMRs) are important criteria for attempting treatment-free remission, an important goal for pts in 1L. However, in 1L, only about 30% of pts treated with imatinib and 30%-55% of pts treated with a 2G TKI achieve MR 4.5 (BCR-ABL1levels on the International Scale≤0.0032%). More than 50% of pts with CML-CP treated with imatinib develop resistance or intolerance to therapy. Among pts treated with a 2G TKI in 1L, 30%-40% need to change therapy by 5 years. Therefore, new treatment options are needed to help pts achieve their treatment goals in 1L. The main treatment goal for all pts is achievement of disease control, which potentially requires lifelong treatment. Therefore, highly potent, safe treatment options are needed for newly diagnosed pts with CML-CP. Asciminib is an investigational drug that inhibits the BCR-ABL1 oncoprotein through a novel mechanism of action: specifically targeting the ABL myristoyl pocket (STAMP). Due to asciminib's specifically targeting the ABL kinase family (ABL1, ABL2, BCR-ABL1), asciminib monotherapy offers the potential to improve safety and tolerability vs TKIs that target the adenosine triphosphate binding site of BCR-ABL1 and thus have varying degrees of selectivity toward ABL kinases. Asciminib has shown promising efficacy and safety in heavily pretreated adult pts with CML in phase I and III trials. In a phase III trial for pts with CML-CP treated with ≥2 prior TKIs, major molecular response (MMR) was achieved by 25.5% of pts on asciminib (40 mg twice daily [BID]) vs 13.2% on bosutinib at week 24. In the phase I trial of asciminib monotherapy at doses of 10-200 mg BID and 80-200 mg once daily (QD), 48% of pts with CML-CP treated with ≥2 prior TKIs without T315I mutations achieved or maintained MMR by 12 months. Here we present the upcoming phase III trial evaluating asciminib 80 mg QD monotherapy vs an investigator-selected approved TKI in newly diagnosed adult pts with CML-CP. OBJECTIVE: The primary objectives of this study are to assess the efficacy of asciminib vs an investigator-selected TKI (either imatinib, bosutinib, dasatinib, or nilotinib) in 1L and to compare the efficacy of asciminib within the stratum receiving investigator-selected imatinib in 1L through the primary end point of MMR rates at week 48. DMRs and; other long-term outcomes are also of interest. DESIGN: This is a multicenter, open-label, randomized, phase III study of asciminib at 80 mg QD compared with an approved, investigator-selected TKI (either imatinib, bosutinib, dasatinib, or nilotinib) for adult pts with newly diagnosed CML-CP in 1L (expected N=402; NCT04971226). Pts may not have received prior TKI therapy for CML, with the exception of ≤2 weeks of imatinib therapy and must have Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1. Pts who have previously received hydroxyurea or anagrelide may be included. Pts will be randomized 1:1 to the asciminib and investigator-selected TKI arms using 2 strata: European Treatment and Outcome Study (EUTOS) long-term survival (ELTS) risk score and the control arm TKI selected by the investigator prior to randomization (Figure 1). Pts randomized to the investigator-selected TKI arm will receive their selected TKIs at approved doses: imatinib, 400 mg QD; bosutinib, 400 mg QD; dasatinib, 100 mg QD; or nilotinib, 300 mg BID. Pts will remain on study for 5 years after the last pt first treatment has occurred, unless they have discontinued early due to treatment failure, disease progression, intolerance, or investigator or pt decision. Pts who discontinue early will continue to be followed up for survival and disease progression until the end of the study. MAIN OUTCOMES: The primary end point is MMR at week 48. Key secondary end points include MMR at week 96; exploratory end points include biomarker assessments. CONCLUSIONS: This study will assess the efficacy of asciminib 80 mg QD in adult pts with newly diagnosed CML-CP vs currently approved TKIs in 1L. This study is sponsored by Novartis. Figure 1 Figure 1. Disclosures Cortes: Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Hochhaus: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding. Takahashi: Kyowahakko-Kirin: Research Funding; Ono: Research Funding; Asahikasei: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eizai: Research Funding; Toyamakagaku: Research Funding; Chugai: Research Funding; Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Larson: CVS/Caremark: Consultancy; Gilead: Research Funding; Astellas: Consultancy, Research Funding; Rafael Pharmaceuticals: Research Funding; Epizyme: Consultancy; Takeda: Research Funding; Novartis: Research Funding; Cellectis: Research Funding. Issa: Syndax Pharmaceuticals: Research Funding; Kura Oncology: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Bombaci: CML Advocates Network: Consultancy, Current Employment, Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; MPN Advocates Network: Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; AIL - Associazione Italiana contro le Leucemie, i Linfomi e il Mieloma ONLUS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; CLL Advocate Network: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Organizational Grant Funding; Novartis: Consultancy, Other: Organizational Grant Funding; Jazz: Consultancy, Other: Organizational Grant Funding; Ceogene: Consultancy, Other: Organizational Grant Funding; Incyte: Consultancy, Other: Organizational Grant Funding; Takeda: Consultancy, Other: Organizational Grant Funding. Ramscar: Novartis: Current Employment. Kapoor: Novartis: Current Employment, Current equity holder in publicly-traded company. Ifrah: Novartis: Current Employment. Hughes: Novartis: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria.

In CML, treatment-free remission (TFR) refers to having a stable deep molecular response without the need for ongoing tyrosine kinase inhibitor treatment. Whilst recommendations exist about the technical management of stopping and re-starting therapy, much is still unknown about the experiences of those considering and undertaking TFR. This study sought to obtain the patient perspective, identify areas of unmet needs and create recommendations for improvements. Fifty-six percent of patients reported fear or anxiety during treatment discontinuation, whereas only 7% of patients were asked if they needed psychological support during this period. Where patients re-initiated treatment; 59% felt scared or anxious, and 56% felt depressed. Twenty-six percent of re-initiated patients received psychological and/or emotional support at this time. Sixty percent of patients experienced withdrawal symptoms whilst discontinuing treatment, however, 40% of patients who experienced withdrawal symptoms reported that they were not fully supported by their doctor in managing all the symptoms. Healthcare professionals should further consider how they monitor the psychological well-being of patients who are discontinuing or re-initiating treatment, and review what support is offered in response to identified concerns. Surveillance of withdrawal symptoms should be a priority during treatment discontinuation, along with how healthcare professionals assist in the management of these.

Background and aims: The use of Tirosine Kinase Ihnibitors (TKIs) for the treatment of Chronic Myeloid Leukemia (CML) has definitely represented a turning point in the treatment of the onco-hematological diseases. Over the years, the interest of physicians, nurses, patients and caregivers has increasingly focused on the aspects of the humanization of care, the management of side effects and on the full and constant therapeutic adherence.The aim of the project was to define patient-oriented care processes, based on a proactive approach that can fully respond to the new health needs of CML patients.Methods: A nursing expert Working Group (WG) was established. WG reviewed literature about CML patients assistance and then it was conducted a survey on organizational models for the treatment of CML patients, adopted by Italian haematologic and transplant centers. Finally, the main issues regarding CML patients care were identified and discussed on a multiprofessional basis.Results: Euriclea Project for care of CML patients with the description of a new and expanded nurse role was defined. The Nurse Case Manager or Nursing Clinical Experts were identified as key people for the management of the side effects of treatment, the promotion of the therapeutic adherence and the evaluation of efficacy and effectiveness of the process through the identification of specific indicators for structure, process and outcome. Discussion: The focal areas of the care process were identified so as to define a different approach to the CML patient, through a holistic view of care and the multidisciplinary interventions.

Optimal adherence to CML therapy is of key importance to maximize treatment effectiveness. Two clinical studies (ADAGIO and Hammersmith) have proven a clear correlation between adherence and achieving optimal treatment response and have revealed that non-adherence is common in CML patients (Marin et al. in J Clin Oncol 28(24):2381–2388, 2010, Noens et al. in Haematologica 99(33):437–447, 2014). The aim of this study is to assess the extent of suboptimal adherence and to investigate motivations and behavioural patterns of adherence in a worldwide patient sample. Questionnaires were provided by the CML Advocates Network and were filled in by patients online and offline. Patient characteristics, treatment and motivations were collected. Adherence was assessed by the 8-item Morisky Medication Adherence scale. Logistic regression models were fitted to investigate the influence of different factors on adherence. Overall, 2 546 questionnaires from 63 countries and 79 CML patient organisations were evaluable. 32.7% of participants were highly adherent, 46.5% were in the medium and 20.7% in the low adherence group. Factors increasing the probability of being in the high adherence group are older age, male sex, management of side effects, only one tablet per day and feeling well informed about CML by the doctor. More than 2 years since diagnosis were significantly lowering the chance as was the use of reminding tools. Living arrangements, multiple medication and personal payment obligations increased the probability to be at least in the medium adherent group. This is the most comprehensive study conducted to date to gain knowledge about factors causing non-adherence in CML. Better information on the disease, medication and management of side effects, supported by haematologists, is key to improve adherence.

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 Conclusions There are opportunities for more communication and support around psychological issues to be given through the provision of information during the decision-making stage, and/or discussions between doctors and patients during the stopping stage. A considerable proportion of patients feel fear or anxiety at some level during stopping treatment, and not all patients who want psychological and/or emotional support receive it. The psychological well-being of patients should be a consideration of healthcare professionals and addressed at all stages of the TFR journey, to ensure patients receive support at the level they want through personalised care. Figure Disclosures Sharf: Incyte: Honoraria, Other: Advocacy Advisory Board, Research Funding; Abbvie: Other: Advocacy grants funding; Roche: Other: Advocacy grants funding; BMS: Other: Advocacy grants funding, Research Funding; Takeda: Other: Advocacy grants funding; Janssen: Other: Advocacy grants funding; Novartis: Honoraria, Other: Advocacy Advisory Board, Research Funding; Pfizer: Honoraria, Other: Advocacy Advisory Board, Research Funding. Hochhaus:Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; MSD: Research Funding; Incyte: Research Funding. Geissler:Pfizer: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy; Takeda: Research Funding; Amgen: Consultancy; Incyte: Research Funding; Roche: Consultancy; Servier: Consultancy; UCB: Consultancy, Speakers Bureau. Marin:Leukemia Patient Advocates Foundation: Employment. Pemberton-Whiteley:Acute Leukemia Advocates Network (ALAN): Consultancy; CML Advocates Network: Membership on an entity's Board of Directors or advisory committees; Patient Evidence: Equity Ownership; Daiichi Sankyo: Other: Grant funding; Gilead: Other: Grant funding, Speakers Bureau; Incyte: Consultancy, Other: Grant funding; Jazz: Other: Grant funding, Speakers Bureau; Janssen: Consultancy, Other: Grant funding; Kyowa Kirin: Other: Grant funding; Novartis: Consultancy, Other: Grant funding, Speakers Bureau; Pfizer: Consultancy, Other: Grant Funding, Speakers Bureau; Takeda: Other: Grant funding; Shire: Other: Grant Funding; 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; Leukaemia Care: Employment. Bombaci:CLL Advocate: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: grant funding ; CML Advocate: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Grant funding ; Incyte: Consultancy; Onlus: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: grant funding; Novartis Pharma AG: Consultancy, Other: Advisory board ; MPN Advocate: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: grant funding ; Abbive: Consultancy, Other: grading funding; Bristol- Myers: Consultancy, Other: Grant Funding; Jazz: Consultancy, Other: Grant funding ; janssen: Consultancy, Other: grant funding. Christensen:Novartis: Consultancy, Other: Advisory Board; Incyte: Consultancy, Other: Advisory Board. Gouimi:AMAL: Membership on an entity's Board of Directors or advisory committees; Novartis Pharma: Consultancy, Other: Advisory Board; Bristol-Myers: Consultancy; Novartis: Consultancy, Other: funding grant; Takeda: Consultancy; Pfizer: Consultancy. Deekes:Novartis Pharma: Honoraria. Bradley:Quality Health: Employment.

BackgroundHealth-related quality of life (HRQOL) is a key aspect for chronic myeloid leukemia (CML) patients. The aim of this study was to develop a disease-specific HRQOL questionnaire for patients with CML to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30.Patients and methodsThe process followed a predefined and systematic stepwise iterative process as defined by the EORTC guidelines for questionnaire development. The process was divided into 3 phases: (1) generation of relevant HRQOL issues, (2) operationalization of the HRQOL issues into a set of items, and (3) pretesting the questionnaire for relevance and acceptability. Descriptive statistics and psychometric analyses were also performed.ResultsOverall, 655 CML patients were enrolled in 10 countries including the USA and countries in Europe and Asia. Interviews with health-care professionals experienced in CML (n = 59) were also conducted. Results from the interviews, clinical experiences, and statistical analyses were used to develop the EORTC QLQ-CML24. The final module consists of 24 items assessing the following aspects: symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life. Internal consistency, assessed with Cronbach’s alpha coefficients, ranged from 0.73 to 0.83 for the proposed scales.ConclusionThe EORTC QLQ-CML24 is an internationally developed HRQOL questionnaire for CML patients, and its implementation in clinical research and practice can provide important information to facilitate clinical decision-making.Keywords: Quality of life, Chronic myeloid leukemia, Questionnaire

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 Discussion Despite there is clear evidence that survival is close to that of the general population when CML is treated effectively in chronic phase with current therapies, every fifth CML patient deliberately skips doses. Key factors predicting intentional non-adherence can potentially help physicians and patient organisations to identify patients early who should be monitored more closely and informed about the importance of adherence. Managing side effects proactively also reduces reasons for intentional non-adherence. Disclosures: Geissler: Novartis: Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Efficace:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy. Bombaci:Ariad: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. de Jong:Novartis: Membership on an entity’s Board of Directors or advisory committees. Gavin:Celgene: Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Daban:Ariad: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Pelouchová:Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Sharf:Pfizer: Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees.