Milayna Subar

Predictors of performing response monitoring in patients with chronic-phase chronic myeloid leukemia (CP-CML) in a prospective observational study (SIMPLICITY).

116 Background: Previous SIMPLICITY data (ASCO 2014) have shown, in CP-CML patients (pts) with at least 12 months (mths) follow-up, monitoring for cytogenetic response (CyR) and molecular response (MR) differs from NCCN/ ELN recommendations and shows regional and practice-type variation. Few data describe predictors of monitoring. METHODS SIMPLICITY is an ongoing observational study of CP-CML pts receiving first-line (1L) imatinib (IM), dasatinib (DAS) or nilotinib (NIL) in the United States (US) and Europe (Eu); its primary objective is to understand tyrosine kinase inhibitor (TKI) management patterns in clinical practice (NCT01244750). Frequency of testing for CyR, by FISH or karyotype, and MR, by PCR, were analyzed in 3, 6 and 12 mth increments from TKI start. Stepwise multivariable logistic regression was performed to assess predictors of monitoring (including: age, sex at birth, region, practice type, 1L TKI, ECOG performance status, still on 1L TKI). RESULTS 1,083 pts (US: 66%; Eu: 34%) were enrolled prospectively through 1Apr2014, receiving IM (n=415), DAS (n=343) or NIL (n=325). 1,050, 985 and 862 pts were followed for at least 3, 6 and 12 mths, respectively. Of these, 15%, 34% and 49% were tested for CyR, and 27%, 65% and 83% were tested for MR, between 0-3 mths, 0-6 mths and 0-12 mths. By 3 mths, 33% had either CyR and/or MR testing and 88% of pts underwent testing by 12 mths. None of the candidate predictors distinguished between pts who were monitored vs. those that were not by 3 mths after start of 1L TKI. Pts <65 years (yrs) at start of 1L TKI (odds ratio [OR]=1.41) and those in Eu vs. US (OR=1.45) were more likely to be monitored by 6 mths. By 12 mths, pts <65 yrs (OR=2.27), those no longer on 1L TKI (OR=1.96), and those seen in academic centers (OR=1.59) were more likely to be monitored (all p<.05). A comparison of monitoring patterns with ELN/NCCN recommendations will also be presented. CONCLUSIONS Two-thirds of pts were not monitored for CyR or MR within 3 mths of TKI start.Although there were no predictors of monitoring for CyR or MR by 3 mths, age <65 yrs at initiation of 1L TKI was a consistent predictor of monitoring by 6 and 12 mths. CLINICAL TRIAL INFORMATION NCT01244750.

Quality of Survival: A New Concept Framework to Assess the Quality of Prolonged Life in Cancer

ABSTRACT Background: Improved cancer care means that more patients are surviving longer, but there is a need to examine how well patients survive. We conducted an exploratory analysis of a new conceptual framework termed ‘quality of survival’ (QoS) that delineates the quality of patients’ experience. Methods: This project included an electronic database search to investigate the survivorship landscape and to create a visual QoS map and semi-structured interviews with patients (n = 35), clinicians (n = 40), and payers (n = 7) to support the QoS map. QoS was discussed in the context of two tumor types, metastatic non-small cell lung cancer and metastatic melanoma. Results: Despite increased long-term survival, no specific definition of QoS exists. Patients reported many impacts that affect QoS, clinicians viewed QoS as relevant to treatment decisions, and payers felt it could help communicate different aspects relevant to the patient. Four interconnected QoS dimensions were developed (quality of life, survival, side effects, and economic impact), which vary in importance along the care continuum. Conclusion: QoS is a patient-centric concept that could help decision-making and patient communication. The QoS map could provide a framework to monitor patient experience and help patients frame what treatment attribute is most important to them at any point in the cancer continuum.

Cell-type-specific transcriptional regulation of PIGM underpins the divergent hematologic phenotype in inherited GPl deficiency.

A rare point mutation in the core promoter -270GC-rich box of PIGM, a housekeeping gene, disrupts binding of the generic transcription factor (TF) Sp1 and causes inherited glycosylphosphatidylinositol (GPI) deficiency (IGD). We show that whereas PIGM messenger RNA levels and surface GPI expression in IGD B cells are low, GPI expression is near normal in IGD erythroid cells. This divergent phenotype results from differential promoter chromatin accessibility and binding of Sp1. Specifically, whereas PIGM transcription in B cells is dependent on Sp1 binding to the -270GC-rich box and is associated with lower promoter accessibility, in erythroid cells, Sp1 activates PIGM transcription by binding upstream of (but not to) the -270GC-rich box. These findings explain intact PIGM transcription in IGD erythroid cells and the lack of clinically significant intravascular hemolysis in patients with IGD. Furthermore, they provide novel insights into tissue-specific transcriptional control of a housekeeping gene by a generic TF.

The Quality of Survival (QoS): A concept framework to assist communication and decision making about cancer care.

78 Background: The past decade has seen the development of transitional, novel cancer therapies that lengthen survival, yet data regarding the quality of that survival are limited or unavailable. Improving patient (pt)/healthcare professional (HCP) communication about issues such as QoS might enhance engagement and inform decision-making about future care. For example, the PROACT study (ECC 2015, abs.1715) has shown how little attention is given to family caregiver impact. Our objective is to develop an inclusive framework that will go beyond existing pt-reported outcomes and quality of life (QoL) constructs, and which HCPs may use to communicate with pts. METHODS An electronic database search to investigate the QoS landscape in cancer was conducted and results were articulated into a visual concept map. Subsequently, 20 US pts with metastatic NSCLC were interviewed about their cancer experiences (a similar melanoma pt survey is ongoing) and this input was integrated into the concept map. Areas explored include: symptoms, disease/treatment communication and education, pt expectations about treatment goals and involvement in decision-making, and impacts of all these on pts, families, and friends. RESULTS In their interviews, pts reported a host of impacts: physical, psychological/emotional, social/relationship, work, and financial. A QoS concept framework was developed to capture the holistic pt experience throughout the continuum of cancer care (during and post treatment) and consisted of 4 interconnected domains: QoL, survival, side effects and economic impact. The severity and persistence of some of the impacts ultimately affect survival, while others affect the ability to preserve or return to normality. CONCLUSIONS While pt experiences are usually discussed and monitored by HCPs, issues identified as most important to pts and families and their variability over time, are rarely assessed formally during survival. These findings support the development of a pt-centric concept map that defines QoS, provides a comprehensive framework for improving communication between pts and their care teams about long-term QoS in cancer, and potentially enables better treatment decisions.