ALBERT

Description: The increased recognition of the high prevalence and important burden of cancer pain and the documentation of a large proportion of patients receiving inadequate analgesic treatment should have reinforced the need for evidence-based recommendations. The World health Organization (WHO) guidelines on cancer pain management—or palliative care—are traditionally based on a sequential, three-step, analgesic ladder according to pain intensity: nonopioids (paracetamol or nonsteroidal anti-inflammatory drugs) to mild pain in step I; weak opioids (eg, codeine or tramadol) to mild-moderate pain in step II; and strong opioids to moderate-severe pain in step. III. Despite the widespread use of this ladder, unrelieved pain continues to be a substantial concern in one third of patients with either solid or hematologic malignancies. The sequential WHO analgesic ladder, and in particular, the usefulness of step II opioids have been questioned but there are no universally used guidelines for the treatment of pain in patients with advanced cancer and not all guideline recommendations are evidence-based. The American Society of Clinical Oncology and the European Society of Medical Oncology have recommended the implementation of early palliative care (EPC), which is a novel model of care, consisting of delivering dedicated palliative service concurrent with active treatment as early as possible in the cancer disease trajectory. Improvement in cancer pain management is one of the several important positive effects following EPC interventions. Independent well-designed research studies on pharmacological interventions on cancer pain, especially in the EPC setting are warranted and may contribute to spur research initiatives to investigate the poorly addressed issues of pain management in non cancer patients.

Description: Background: Understanding health-related quality of life (HRQOL) profile, including functional aspects and symptom burden, of yet untreated patients with myelodysplastic syndromes (MDS) is important to help clinicians to better identify subgroup of patients in need of special attention from the very beginning of therapy. Aims: The primary objective of this study was to investigate baseline (i.e., pretreatment) HRQOL profile of untreated patients with lower-risk MDS, examining differences by age, gender, risk score category and comorbidity. A secondary objective was to provide age and sex baseline reference HRQOL values, according to the EORTC QLQ-C30 questionnaire, to be used as benchmark comparisons in future MDS studies. Methods: This analysis is based on 443 newly diagnosed adult MDS patients with International Prognostic Scoring System (IPSS) risk score of low (46 %) or intermediate-1 (54%), enrolled in an international prospective cohort observational study. Median age was 75 years (range 32-94), with 261 men (59%) and 182 (41%) women. HRQOL was assessed by the EORTC QLQ-C30 questionnaire at study entry, before any treatment (except for transfusions). This well validated questionnaire consists of five functioning scales: physical, role, emotional, cognitive and social; three symptom scales: fatigue, nausea/ vomiting and pain; six single item scales: dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact; and the global health status/HRQOL scale. The items were scaled and scored using the recommended EORTC procedures. At the time of baseline HRQOL assessment, 111 (25%) patients had received at least one red blood cell transfusion. We used Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for all comparisons. We used the false discovery rate approach to account for multiple testing, with a nominal α-level=0.05. In addition to statistical significance, clinically relevant HRQOL differences were also evaluated based on previously published criteria (Cocks K, et al, J Clin Oncol 29:89-96, 2011). Results: There were not statistically significant differences in any of the HRQOL scales measured by the EORTC QLQ-C30, by the specific IPSS risk category (i.e., low risk vs intermediate-1 risk score). Overall, women reported worse HRQOL scores than men, with clinically relevant differences for physical (Δ=-7.1, P=0.002), role (Δ=-9.9, P=0.002) and emotional functioning, (Δ=-10, P

Description: Background: Disease-specific measures of quality of life (QOL) can allow for improved assessment of disease-specific symptomatology and psychosocial factors. We recently reported on the development of the QUALMS, a 33-item QOL assessment tool for patients with myelodysplastic syndromes (MDS). We now report preliminary internal consistency and validity results from an international prospective study. Methods: From December of 2013 to July of 2014,an international cohort of MDS patients completed the QUALMS as well as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy Anemia Scale (FACT-An). Eligible patients were 18 or older, and had to have biopsy-proven MDS; those who had undergone stem cell transplantation were excluded. Baseline medical record review was performed at the time of enrollment to document key clinical and laboratory data, including bone marrow pathology and treatments; a second QUALMS administration and medical record review is planned for each patient to assess responsiveness. Participants were recruited from MDS centers across the United States, Canada and Italy. Individual QUALMS items were scored on a 5-point scale ranging from “Never” to “Always”. Overall mean score was calculated by transforming the raw mean to a 100 point scale, with higher scores indicating better MDS-related QOL. Baseline QUALMS scores were compared to clinical factors such as hemoglobin (Hg) and transfusion dependence as well as with scores on the other QOL scales. Preliminary exploratory factor analysis was also undertaken to identify candidate subscales. Results: As of this analysis, 201 patients had enrolled. The mean age was 71.7 years; there were 55% men, and the IPSS distribution was 44% LO, 43% INT-1, 10% INT-2, 1% HI and 2% unclassifiable. The majority of patients (53%) were receiving an erythropoiesis-stimulating agent, hypomethylating agent or lenalidomide, and 29% of the overall cohort was transfusion-dependent. The geographical distribution was as follows: 20% from the Dana-Farber Cancer Institute (Boston, MA); 9% from Columbia University (New York, NY); 15% from the Moffitt Cancer Center (Tampa, FL); 25% from the Odette Cancer Center (Toronto, Canada); and 31% from two GIMEMA hospitals (Rome and Sardegna, Italy). Scores on the QUALMS ranged from 19 to 78; the mean and median scores were 49.6 and 50.0 respectively. The measure had excellent internal consistency (α=.91), and was moderately correlated with the EORTC QLQ-C30: correlations (r’s) with the global health status scale, functional scales (i.e., physical, role, emotional, cognitive and social) as well as fatigue, nausea and pain scales ranged from 0.33 to 0.63 (all p’s

Description: Abstract 4953 Background: Shared decision-making between patients and physicians is broadly advocated in medicine, however little research is available to understand whether this approach would be desirable to all patients regardless of disease type and severity or individual patient characteristics. While clinical decision-making in high-risk myelodysplastic syndromes (MDS) is critical for a number of reasons including: associated comorbidity, symptom burden, and limited life expectancy, no evidence-base data currently exist on patients' preferences. Aim: The objective of this study is twofold: 1) to investigate to what extent high-risk MDS patients prefer to be involved in treatment decision making during consultation just after diagnosis; 2) to identify possible clinical, socio-demographic and patient-reported health status factors associated with patients' preferences for involvement in treatment decisions. Patients and Methods: Data were gathered through an ongoing international prospective observational study involving 15 countries that recruits newly diagnosed patients with intermediate-2 or high-risk IPSS score. All patients were classified according to the WHO histology classification. During the first encounter with their treating physicians, discussing treatment options just after diagnosis, patients were administered a previously internationally validated “control preference scale”. This scale broadly categorizes patients into one of three roles depending on the extent of their preferred involvement in treatment decision-making: “active” (where the patient themselves prefer to decide on which would be the most appropriate treatment option for themselves); “collaborative/shared” (where the patient and the doctor jointly decided on the most appropriate treatment option); “passive” (where the patient prefer to leave decision on the most appropriate treatment option to the doctor). Associations with the following variables were investigated: performance status, comorbidity (“Hematopoietic Cell Transplantation”-“Comorbidity index”), living arrangements, age, gender, education, cultural group, IPSS risk category, evolution from lower IPSS risk scores and patient-reported symptoms (using symptom scales of the EORTC QLQ-C30). Descriptive statistics were used and Mann-Whitney U-test, Kruskall-Wallis test and Fisher's exact test were used as appropriate to test statistical significance of performed comparisons. Results: Study population included overall 121 patients (38% female and 62% male). Mean age of patients was 69 years (min:31.3 max: 87.9) and 80% were diagnosed with IPSS int-2 risk score and 20% with IPSS high risk score. Twenty-six percent evolved from lower IPSS risk scores, while 74% were newly diagnosed with higher-risk. Forty-nine percent favored a passive while only 13% preferred an active role in treatment decision-making; the remaining 38% favored a collaborative/shared decision-making approach. Investigation of factors possibly related to preferred roles, found that passive role was significantly associated with lower education levels (P=.04). Among lower educated patients, 62.5% preferred a passive role compared with only 5% preferring an active role. When investigating relationships with patient-reported symptoms, a general trend for patients preferring a passive role, showing worse outcomes, was also evident. Higher symptom mean scores were found for passive vs. active role groups, being respectively: 46 (sd.26.6) vs. 37 (sd.29.9) for fatigue; 20 (sd.31.8) vs. 2 (sd.8.6) for constipation; 34 (sd.33) vs. 24 (sd.29.5) for dyspnea. Exploratory analysis showed that overall mean symptom score was statistically significant worse in patients preferring a passive role vs. those preferring an active role (P=.01). While other trends of associations were noted, these were not statistically significant. Conclusion: This is the first evidence suggesting that a consistent percentage of high-risk MDS patients prefer a passive role when discussing treatment options with their treating physicians at the time of diagnosis. There is also an indication that these patients are those with lower education levels and presenting with a higher symptom burden. Results need to be confirmed in a larger sample size. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3423 Background: Ensuring the highest possible standards of health-related quality of life (HRQOL) in patients with CML is now one of the top priorities of clinical research. There are several examples of how HRQOL data have contributed in better understanding overall treatment effectiveness in patients diagnosed with cancer malignancies. However, no evidence exists regarding the amount and the quality HRQOL research conducted in CML patients. Aim: The main objective of this paper is to systematically review all evidence-base data available, published over the last twenty years, stemming from studies focusing on HRQOL and other patient-reported outcomes (PROs) in CML patients. Materials and Methods: A systematic review broadly following the Cochrane methodology was performed. A literature search was undertaken in a number of databases by two independent reviewers. The following databases were used: PubMed (1980- October 2009), Cumulative index of Nursing and Allied Health Literature (CINHAL), SCOPUS (1980-2009), PsycINFO and PsycARTICLES (1980-2009). Additional literature was identified via the reference lists of these articles and a search of references was also performed by hand. Key experts in the field of hematological research were contacted. Candidate articles were then also independently scrutinized for possible inclusion. Any original article including a HRQOL evaluation or any other type of PROs (according to the current definition by the Food and Drug Administration) was considered. Any study regardless of the treatment, design and type of analysis (quantitative or qualitative) was considered eligible. No restrictions in the number of patients enrolled was applied. All studies meeting the criteria were then independently evaluated by two reviewers on their methodological quality according to a previously developed protocol. This included a number of methodological and statistical quality criteria such as questionnaire used, timing of assessment, missing data documentation, and discussion of HRQOL outcomes in terms of clinical significance. Results: Over 350 articles were scrutinized for possible inclusion in the review and 15 met inclusion criteria. No studies were published before 1995 and 10 studies (67%) were published after year 2000. Six studies (40%) dealt with interferon (IFN) based-treatments, 7 (47%) with bone marrow transplantation (BMT) and 2 (13%) with targeted therapies. Only 5 (33%) studies included an overall sample of more than 100 CML patients thus providing more confidence on HRQOL analysis. The EORTC QLQ-C30 was the most frequently used HRQOL measure being employed in 4 (27%) studies. Evidence stemming from studies comparing IFN with conventional hydroxyurea or busulfan treatments highlighted major HRQOL impairment associated with IFN even in the long run. These were particularly evident in a number of functional areas: cognitive, social, and sexual functioning as well as for symptoms: fatigue, pain and dyspnea, nausea/vomiting, flu-like and febrile, skin problems. Neuropsychological limitations and mood disorders were also found to be associated with IFN based-therapy. As concern BMT, current evidence suggests that even in the long run (i.e. 10 years after transplantation) physical limitations are still evident when compared to age matched general population norms. Although two studies dealing with targeted therapies were found to have included a HRQOL component in the study design, only one fully documented HRQOL outcomes. This was a randomized controlled trial (IRIS Study) (HRQOL being used a secondary endpoint) showing a clear advantage in terms of HRQOL of Imatinib over IFN based therapy. The difference between treatment arms (IM vs. IFN) was not only statistically significant but also clinically meaningful and with a large effect size (ES=1.05). Conclusions: HRQOL evidence base data is scarce in CML patients. The main conclusion that can be drawn is that IM offer major advantages in terms of HRQOL compared with IFN based therapies. However, long-term HRQOL data of IM therapy are needed to determine the impact of therapy over the long run from the patients' perspective. We expect patient-reported HRQOL becoming more and more a crucial outcome to fully evaluate overall treatment effectiveness of future therapeutic approaches in this area. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Patients myelodysplastic syndromes (MDS) diagnosed with higher-risk disease have poor prognosis thus making improvements in health-related quality of life (HRQOL) a major goal of therapy. Understanding HRQOL profile of untreated patients is important to help clinicians to better target subpopulations in need of special attention from the very beginning of therapy. Aims: The primary objective of this study is to investigate whether HRQOL differences exist by age and gender in untreated patients with higher-risk MDS. A secondary objective is to provide age and gender pretreatment HRQOL profiles to be used as reference baseline data for comparing HRQOL of MDS patients under treatments. Methods: This analysis is based on 280 adult patients diagnosed with IPSS risk score of intermediate-2 (74%) and high-risk (26%), enrolled in an international prospective observational study. Median age of patients was 71 years (range 32-89), 176 were men (63%) and 104 (37%) women. HRQOL was assessed at study entry and before treatment for higher-risk disease (except for transfusions), with the EORTC QLQ-C30, the most widely used HRQOL outcome measure in MDS research. Thus, our data are likely to further ease interpretation of outcomes in many studies using this questionnaire. One hundred seventy-five patients had received at least one red blood cell transfusion at the time of baseline HRQOL assessment. HRQoL data of MDS patients were age-gender matched with those general population norms. Wilcoxon-Mann-Whitney and Wilcoxon signed ranks tests were used for unmatched and matched comparisons, respectively (α=0.05). Effect sizes were also computed. Results: No statistically significant differences existed in any of the HRQOL domain by IPSS category (intermediate-2 versus high-risk). However, HRQOL profiles differed by age and gender and results are reported in Table 1. Women generally reported lower HRQOL scores than men, with statistically significant impairments in the global quality of life (P=0.008), role (P=0.014), emotional (P=0.024) and social functioning (P=0.028). When compared to their peers in the general population, HRQOL was found to be impaired in all age group categories (Figure 1, A and B). However, the magnitude of impairments across HRQOL domains was markedly larger in younger patients (aged 30-59 years) compared to older age groups (≥60 years). The top three largest impairments in this younger group were found for: fatigue (ES=2.47, P

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: One of the main challenges in the treatment of chronic myeloid leukemia (CML) is the selection of second line therapy. While Nilotinib (NILO) and dasatinib (DASA) are available for use as second line treatment for several years, few evidence-based data is available on how physicians make decisions on the use of one drug over another. Aim: We performed a pilot study to describe which factors physicians consider most relevant when deciding therapy with either NILO or DASA in patients who previously failed or were intolerant to Imatinib (IMA) therapy. Patients and methods: Analyses are based on a sample 67 CML patients, recruited as part of a larger international study, who switched from IMA therapy to either NILO (N=36; 53.7%) or DASA (N=31; 46.3%). Patients had to be in second line treatment for at least three months to be eligible for this analysis. Also, in all participating centers, NILO and DASA should have been equally available for use. There were 15 physicians involved in the management of these patients and they were asked to complete an ad-hoc questionnaire investigating reasons based on which they made the decision to either use one drug over another. All questions were phrased as follows: "To what extent have the following issues been determinant to make a decision on which agent (NILO or DASA) to use for this patient?" All answers were rated on a four point likert-scale (ie, not at all, a little, quite a bit and very much). Items investigated were: 1) accessibility of the drug in the hospital; 2) cost of drug; 3) patients' comorbidities; 4) patients' age; 5) patients' personality profile; 6) discussion with patients about Pro and Cons; 7) different treatment schedule of drugs; 8) type of mutation during IMA therapy. Physician characteristics were also collected and analyzed. Other treatment-related variables were investigated such as main reason for changing of TKI (IMA intolerance or resistance), high grade adverse events (AEs) experienced during IMA treatment, or previous duration of IMA therapy. Results: Physicians' experience in treating CML patients was on average 14 years (range 4-32). Patient median age at the time of treatment switch was 47 and 55 years in the NILO and DASA group, respectively. Median time of duration of IMA therapy, before receiving second line therapy, was 1.4 years and 3.3 years for those who switched respectively to NILO or DASA. No differences existed between groups with regard to reasons for switching from IMA therapy (intolerance or resistance) or AEs reported with previous IMA therapy. The top issue considered as most relevant when making the decision was previous discussion with patients on advantages and disadvantages of drugs, being reported as "quite a bit" and "very much" important in 73% of evaluations. Cost of the drug was not considered relevant at all, in the selection of which drug to use, in 97% of the 69 evaluations considered. Also, type of mutation during IMA therapy was considered as of negligible relevance for the decision, but it should not be overlooked that mutations were detected in few patients. Patient's comorbidity or personality profile was quoted as a 'quite a bit' or 'very much' relevant reason for the selection of 2nd line TKI, respectively in 43% or 48% of all questionnaires. Low relevance was assigned to patient age and different treatment schedule: 'not at all' or 'a little' relevance was reported respectively in 64% and 70% of all questionnaires. The analysis of physician-reported grading distribution according to the type of second line treatment did not show any significant difference (no reason lead to a preferential selection of one drug), see table 1. Conclusions: No differences were detectablein selected factors, driving the decision to switch either to NILO or DASA when physicians consider switching from first line IMA therapy. Also, type of TKI selection does not seems to be guided by only one factor. Further research is needed to elucidate on potential reasons underlying clinical decision making in 2nd TKI selection. Disclosures Efficace: Seattle Genetics: Consultancy; TEVA: Consultancy, Research Funding; Lundbeck: Research Funding; Bristol Myers Squibb: Consultancy. Rosti:Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau. Breccia:Celgene: Honoraria; Pfizer: Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Ariad: Honoraria. Baccarani:Novartis: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau.

Description: Background: Patient-reported outcomes (PROs) play a crucial role in providing patient-centered health care. Inclusion of patients' symptoms, disease perception and quality of life (QoL) provides valuable input for the individual treatment guidance and response evaluation of patients with myelodysplastic syndromes (MDS). Aims: (1) To provide an overview of QoL measurement instruments (QoL-MI) as a multidimensional source of PROs for patients with MDS. (2) To identify core PROs for MDS from the perspective of patients and physicians and to compare the two groups. Methods: (1) To identify studies applying QoL-MI in MDS, we performed a comprehensive systematic literature search (PubMed, Cochrane Library, Scopus, Web of Science). We excluded studies measuring solely one health domain or studies without an English version of the QoL-MI. Studies were screened by two independent reviewers and the observed QoL-MI were summarized in an evidence table. The domains and items within each of the observed QoL-MI were extracted and categorized into potential PROs by six experienced researchers and clinical experts. (2) The selection process included a two-round Delphi survey among MDS patients from France and physicians from 17 different countries as part of the MDS-RIGHT project. Each outcome was scored for importance, using a scale from 1 to 9. Following recommended criteria, highly important outcomes were defined as those scored 7-9 by at least 70% of participants and scored 1-3 by not more than 15%. Outcomes were excluded if scored 1-3 by at least 70% of the participants and 7-9 by not more than 15%. New outcomes were included in the next round if at least two participants suggested them. In the second round, all outcomes were presented together with the ratings of the first round. We used Spearman's rank correlation coefficient to determine the correlation between mean PRO scored by physicians (2nd round) and patients (1st round). Results: (1) Literature search resulted in 2863 studies; 81 studies were included. Overall, we identified twelve generic, six cancer-specific and two MDS-specific QoL-MI. The most commonly used instruments were EORTC QLQ-C30 (26 studies), FACIT-An (17), SF-36 (16), QoL-E (10), and FACIT-BMT (7). These five instruments composed 68% of the total 112 QoL-MI implementations, whereas the MDS-specific QoL-MIs composed only 10%. Based on the QoL-MI review we categorized 40 potential core PROs, which were used in the two-round Delphi survey. (2) In the physicians' Delphi survey, we obtained 38 responses in the first round and 32 responses in the second round. More than 80% of the survey participants had more than ten years of work experience with MDS patients. Three PROs fulfilled the strict inclusion criteria: transfusion dependence, general QoL and ability to work/activities of daily living. After the first round of the patients' survey, 40 answers were analyzed. Confidence in health care, disease knowledge, weakness, general QoL, relationship with friends/relatives, medication use, fatigue, general health, need to rest and shortness of breath were the ten highest ranked PROs. Based on these interim data, most outcomes did not yet fulfill the inclusion criteria and three additional outcomes were suggested: difficulty concentrating, dental problems and fear of falling. The reported low absolute scoring for speaking difficulties, headache, tremor, loss of independence, urinary incontinence and financial difficulties is remarkable. The Spearman coefficients (ρ) showed statistically significant moderate correlation between mean physician and patient scores (ρ=0.51; p-value= 0.0007). Absolute scores differed: patients assigned more often extreme categories (i.e., 1-3 or 7-9) and overall assigned lower importance than physicians. Conclusion: This systematic review demonstrates that the application of QoL scores in MDS patients and the use of MDS-specific QoL-MI are limited so far. Relative PRO-scoring was similar in physicians and patients, but was in general lower in absolute ranking in patients as compared with physicians. However, distinct PROs namely disease knowledge and confidence in health care were identified, which were scored higher by patients than by physicians. These results may form the basis for patient-centered outcome definition. The second patient survey is ongoing and will provide the basis for definition of core PROs in MDS. Disclosures Stojkov: MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time) project: Research Funding; Erasmus Mundus-Western Balkans (ERAWEB) programme: Other: Doctoral scholarship. Conrads-Frank:MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time) project: Research Funding. Rochau:MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time) project: Research Funding. Arvandi:MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time) project: Research Funding. Fenaux:Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Efficace:TEVA: Research Funding; Seattle Genetics: Consultancy; Bristol Meyers Squibb: Consultancy; AMGEN: Research Funding; Orsenix: Consultancy; Incyte: Consultancy; TEVA: Consultancy; Amgen: Consultancy; Lundbeck: Research Funding. Siebert:MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time) project: Research Funding. Stauder:Teva: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Therapy with Tyrosine Kinase Inhibitors (TKIs) changed the fate of Philadelphia-positive Chronic Myeloid Leukemia (CML). At present, the therapeutic strategy aims to improve the management of the disease and the quality of life of the patients. In July 2015, we started a prospective multicentric randomized trial with the aim to validate the policy of the intermittent de-escalation treatment and to explore the impact of this strategy on the Quality of Life. To this purpose, CML patients older than 60 years in stable (≥2 years) MR3.0 or MR4.0 molecular response were randomized to receive a FIXED intermittent TKIs regimen (one month ON and one month OFF), as previously published (Russo D, Blood 2013; Russo D, BCJ 2015), versus a PROGRESSIVE intermittent TKIs regimen (one month ON and one month OFF for the 1st year; one month ON and two months OFF for the 2nd year; one month ON and three months OFF from the 3rd year) (OPTkIMA study, ClinicalTrials.gov: NCT02326311). Molecular monitoring was performed according to the 2015 ELN guidelines, every 3 months by RT-PCR on peripheral blood (Baccarani M,Blood 2013). In case of MR3.0 (MMR) loss, checked in two monthly consecutive RT-PCR analysis, patients were planned to exit the study and to resume TKIs daily. This first interim report have been focused on the patients who, by intention to treat, have completed the first year of the study for an historical comparison with the previous INTERIM trial (Russo D, Blood 2013; Russo D, BCJ 2015). During the first year, both the patients randomized in the FIXED and in the PROGRESSIVE arms were given the TKIs treatment one month ON and one month OFF. Up to June 2018, 177 patients have been enrolled by 26 Italian Hematological Centers (first patient randomized in July 2015) and 121/177 patients (68%) completed the first year of OPTkIMA study. The median age was 71 years (range 60-89) and 64% of the patients were belonging to the Sokal intermediate/high risk goup. 96/121 (79%), 14/121 (12%) and 11/121 (9%) patients were receiving imatinib (IMA), nilotinib (NILO) and dasatinib (DAS), at the time of enrollment. Overall, 59/121 (49%) and 62/121 (51%) patients have been randomized in the FIXED and PROGRESSIVE arm, respectively. 41/62 patients (66%) randomly assigned to the PROGRESSIVE arm have entered the second year of therapy. 34/121 patients (28%) went out of the study during the first year. The reasons for protocol discontinuation were: informed consent withdrawn (2 cases), second cancer (4 cases), loss of MR3.0 (28 cases). (Table 1). Among the 28 patients who lost the MMR, 17 and 11 were in MR4.0 and MR3.0, respectively, when they were enrolled into the study. Thus the probability of loosing the MR3.0 while on OPTkIMA was 21,7% at one year (Figure 1). All the 28 patients resumed TKIs continuously and all obtained at least the MR3.0 response, within 6 months and are currently included in the study follow up. The intermittent treatment was well tolerated, with 4 serious adverse events (1 appendicitis, 1 atrial fibrillation, 1 cardiac failure, 1 hip fracture) and 3 adverse events (1 diarrohea, 1 pruritus and 1 fever), none of which have been considered treatement-related. None of the patients experienced the TKI withdrawn syndrome. According to this first interim report, we found that a policy of intermittent TKIs administration in elderly patients is safe and well tolerated. Analysis of patient-reported QoL outcomes is ongoing and will further add information on the overall treatment effectivness of the new PROGRESSIVE intermittent TKI administration. After the 1st year, 28/121 patients (23%) lost MR3.0 and all of them re-gained the major molecular response within 6 months from resumption of continuous treatment. The probability of MR3.0 loss while on OPTkIMA at 1 year was 21,7% and this is quite comparable with the 20% MR3.0 loss observed in the previous INTERIM trial (Russo D, Blood 2013; Russo D, BCJ 2015). Disclosures Efficace: Bristol Meyers Squibb: Consultancy; Seattle Genetics: Consultancy; Lundbeck: Research Funding; TEVA: Research Funding; AMGEN: Research Funding; Incyte: Consultancy; Amgen: Consultancy; TEVA: Consultancy; Orsenix: Consultancy. Abruzzese:Novartis: Consultancy; BMS: Consultancy; Pfizer: Consultancy; Ariad: Consultancy. Bonifacio:Incyte: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Novartis: Research Funding; Bristol Myers Squibb: Consultancy. Castagnetti:Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Giai:Novartis: Consultancy; Pfizer: Consultancy.