Ultra-high Risk Group Research Articles

P916: COEXISTENCE OF ≥2 HIGH-RISK MOLECULAR ABNORMALITIES SUPERVENES THE PROGNOSTIC VALUE OF THE REVISED INTERNATIONAL STAGING SYSTEM FOR MYELOMA: REAL-WORLD DATA ANALYSIS FROM THE GREEK MYELOMA STUDY GROUP

Background: Revised International Staging System (R-ISS) has improved the prognostic value of ISS in multiple myeloma (MM). Recently, the Mayo Additive Staging System incorporated +1q21 to determine a 5-factor 3-tier system, providing an add-on value on R-ISS. The prognostic impact of the coexistence of ≥2 high-risk molecular abnormalities, including +1q21, compared to R-ISS, has not been validated adequately. Aims: The aim of this study was to evaluate the prognostic impact on survival of the coexistence of ≥2 high-risk molecular abnormalities, defined as Ultra High Risk (UHR) MM, in comparison with R-ISS and other established prognostic markers, in the real-world setting. Methods: We analyzed the data of 1352 consecutive newly diagnosed MM patients (M/F: 655/697, median age: 66, range: 29-87, IgG: 817, IgA: 363, light chain: 144, IgD: 9, IgM: 3, non-secretory: 16), treated between 2002-2021 and which had been tested for molecular abnormalities i.e. del17p, t(14;16), t(4;14) and +1q21 using fluorescence in situ hybridization. Patients with ≥2 high-risk features were classified as UHR. We compared the two groups for age, performance status, ISS, R-ISS, lactate dehydrogenase (LDH), albumin, hemoglobin (Hb), β2-microglobulin, estimated glomerular filtration rate (eGFR), 1st and 2nd line therapies and response rates. A Cox regression model was used to determine independent prognostic factors for overall survival (OS). Progression-free survival (PFS) and OS were plotted with Kaplan-Meier; a p<0.05 was considered as statistically significant. Results: One hundred sixteen patients (9%) were classified in the UHR group vs. 1236 (91%) in the non-UHR group; 106 patients had 2, and 10 patients had 3 molecular abnormalities. The most common combination of high-risk features was +1q21 plus t(4;14) (40%). Median age, sex, performance status, LDH and serum albumin, did not differ, whereas the UHR group had lower eGFR, higher β2-microglobulin and lower Hb (p<0.05). Early stage (ISS1/R-ISS1) was more frequent in the non-UHR group (p<0.05); 1st line treatment, including autologous transplantation (ASCT), and second line treatment were well balanced between groups (p<0.05); 66% of patients overall, received triplet/quadruplet combinations and 29% underwent ASCT upfront. Overall response rate after induction therapy was 86% and did not differ between groups (p<0.05). Complete response was lower in the UHR group (11% vs. 19%; p=0.03). After a median follow up of 49 months (95% CI: 44-54), 59% of patients were alive. Median PFS was significantly shorter for the UHR group (15.8 vs. 31.9 months, p<0.001; HR: 0.45, 95% CI: 0.36-0.58). Median OS was 28 months (95% CI:18-38) for patients in the UHR group vs. 69 months (95% CI: 61-77) for others (p<0.001). In the univariate analysis, age, anemia, eGFR, upfront ASCT, R-ISS and UHR myeloma were independent predictors for OS (p<0.05). In the multivariate analysis UHR myeloma was the strongest independent predictor for OS (p<0.001; HR: 0.42), supervening the prognostic value of R-ISS (R-ISS1 vs. R-ISS2 HR=0.58, R-ISS2 vs. R-ISS3 HR: 0.75). Additionally, UHR status singled out a distinct group within R-ISS2 patients with significantly worse OS (38 months, 95% CI: 28-48 vs. 64mo, 95% CI: 55-72) (p<0.001). Summary/Conclusion: According to our analysis of a large cohort of newly diagnosed MM patients UHR myeloma, was the strongest independent predictor for OS, supervening the prognostic value of R-ISS. Moreover, UHR status could serve as an additional prognostic marker for R-ISS2 patients, helping thus to optimize therapeutic approach of MM patients.

Gestational trophoblastic neoplasia: 14-year experience from a single institution.

e17529 Background: Gestational trophoblastic neoplasia (GTN) is a rare tumor with an excellent prognosis. With the advent of multiagent chemotherapy, cure rate improved to nearly 100% in the low-risk group (LR). However, in developing countries it is lower, especially in the high risk (HR) group. Herein, we describe our experience with management and survival of GTN over a 14y period. Methods: Retrospective study based on case review of women with newly diagnosed GTN between 2005 and 2019 at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima- Peru. Primary outcome measure was complete remission (CR) by 12 months following completion of therapy and 3y overall survival (OS). Risk score was established according to the International Federation of Gynecology and Obstetrics (FIGO) with patients with scores &lt; 7 and ≥7 being classified as LR and HR, respectively. A subgroup with score ≥13 was defined as ultra-high risk (UHR) group. Results: 172 patients with GTN were included, median age was 30 years (range 18-54 y). Choriocarcinoma was the most frequent histology in 54.6%, however, in 38% it was not determined. The most common metastatic sites were lungs (66%) and brain (15%). Median FIGO risk score was 10 points (range 1- 21). Accordingly, 8% and 82% of patients belong to LR and HR group; 41% of patients with HR had a score ≥13. Regarding treatment, 5 patients (16%) in the LR group were treated with surgery only and 84% received oral methotrexate; while all patients in the HR group received multidrug chemotherapy: 85% received etoposide, methotrexate and dactinomycin (EMA)/ cyclophosphamide and vincristine (CO), 10.6% received etoposide, methotrexate, actinomycin-D (EMA)/ etoposide and cisplatin (EP) and 2% received other regimens. CR was ultimately achieved in 83% of cases overall (100%, 80% and 73% in LR, HR and UHR group, respectively). 16% had persistent disease and relapse occurred in 5% of patients who had previously achieved CR. Early death (within 4 weeks of initiating therapy) occurred in 4.6% (8/31). 3y-OS was 82%, after excluding early deaths, the survival rate was 86%. Conclusions: In our series, HR disease is the most frequent presentation and almost half of this cases correspond to the UHR group. Remission rate in the LR group is similar to that reported in other series, however it is lower in HR and UHR group. Having said this, it represents the data of a high-risk cohort of patients in a resource-constraint setting. This data is being used to identify strategies for improvement of results, especially in ultra-high risk group.

Assessment of Cognitive Impairment in Early Intervention Settings

Background. Cognitive impairment in schizophrneia is highly prevalent, the level of impairment range from moderate to severe. It has previously beed stated that cognitive impairment was stable through the course of illness, but newer finding from long-term studies indicate that some patient have improved cognitive function. Cognitive function is marginally reactive to antipsychotic medication, and it is highly predictive of poor social and vocational outcome. Also, it constitute a ‘glass ceiling’ for psychosocial and vocational rehabilitation. Several large batteries have been developed, and internationally, there is an attempt to agree on common measurements of core areas. There is a strong rationale for cognitive remediation, namly that it might improve the ability of patients to function in everyday life and that it has no side effects. Individuals at ultra-high risk (UHR) for psychosis have significant cognitive deficits that can impede functional recovery. Methods. In this randomised, clinical trial 146 individuals at UHR for psychosis were randomly assigned to treatment as usual (TAU) or TAU plus cognitive remediation. The CR targeted neurocognitive and social cognitive remediation. Results. A total of 73 UHR individuals were assigned to TAU and 73 assigned to TAU + cognitive remediation. Cognitive remediation did not result in significant improvement on the primary outcome; the Brief Assessment of Cognition in Schizophrenia composite score at 6-month follow-up (b=-0.125, 95%CI: -0.23 to 0.172, p=0.41). Conclusion. The 20-session treatment protocol was not well received in the UHR group. Possibly situations close to everyday life could be better received and be more motivatingDisclosureNo significant relationships.

Improved Uveal Melanoma Copy Number Subtypes Including an Ultra-High-Risk Group.

PurposeTo evaluate the clinical relevance of low-frequency copy number aberrations (CNAs) in uveal melanoma (UM) and to discern residual genomic and clinical heterogeneity within established molecular subtypes based on genome-wide CNA profiling of 921 primary tumors.DesignRetrospective single-center case series.ParticipantsPatients with primary UM referred for genetic testing between 2008 and 2016 (n = 921). The Cancer Genome Atlas cohort with clinical outcome data available (n = 70) was used to validate findings.MethodsGenome-wide CNAs were generated for primary tumors from 921 patients and for 19 metastatic UM (mUM) in the liver. Of the 921 patients, metastatic outcome was known for 678 patients with a median time to metastasis of 4.5 years. The primary tumors were processed on the Affymetrix arrays SNP-5.0 (n = 140), SNP-6.0 (n = 359), or CytoScanHD (n = 422), and the metastatic tumors on the CytoScanHD array (n = 19). Recurrent CNAs were identified, and the prognostic effect of individual CNAs and multiple CNA clustering strategies, including more specific molecular subgroups with rare CNAs, were evaluated.Main Outcome MeasuresCNA recurrence, and effect of CNAs and derived molecular subtypes on metastatic-free survival.ResultsGenomic profiling revealed CNAs associated with risk of metastasis and demonstrated a strong association between chromosomal instability and patient prognosis. Using standard prognostic CNAs, 6 clusters were detected, and inclusion of chromosome 16q deletion revealed an additional cluster. Of these 7 genomic clusters, 5 patient groups showed distinct rates of metastasis, indicating that different genomic patterns can have similar patient outcomes. A small group of patients with a significantly higher rate of metastasis was characterized by monosomy 3, 8q amplification, and deletion of 1p or 16q. Although this ultra–high-risk group accounts for only 7% of this cohort, 88% demonstrated metastasis within 4 years, compared with 45% in the second-highest risk group.ConclusionsThese results suggest that 1p and 16q deletion should be incorporated in clinical assays to assess prognosis at diagnosis and to guide enrollment in clinical trials for adjuvant therapies.

Neurocognition and Social Cognition- Possibilities for Diagnosis and Treatment in Ultra-High Risk for Psychosis State.

In recent decades, clinicians have developed the construct of ultra-high risk (UHR) for psychosis to characterize the prodromal phase of psychosis or classify people with weakly expressed psychotic symptoms. In this conceptual analysis, we have gathered up-to-date data about the clinical picture of neurocognition and social cognition in people at UHR for psychosis. We also discuss treatment options. A well-chosen therapeutic approach can help to deal with difficulties and delay or even prevent the development of full-blown psychotic disorders in the UHR group. Despite much evidence supporting the benefits of therapy, early interventions are still not as widely used as they should be. Thus, a better understanding of the UHR state is very important for all healthcare workers.

Empathy and Its Relationship With Social Functioning in Individuals at Ultra-High Risk for Psychosis.

Introduction: Social functioning is often impaired in the ultra-high-risk (UHR) phase of psychosis. There is some evidence that empathy is also impaired in this phase and that these impairments may underlie difficulties in social functioning. The main aim of this study was to investigate whether cognitive and affective empathy are lower in people in the UHR phase of psychosis in comparison to healthy controls, and whether possible impairments have the same magnitude as in people with schizophrenia. A second aim was to examine whether there is a relationship between empathy and social functioning in individuals in the UHR phase.Method: Forty-three individuals at UHR for psychosis, 92 people with a schizophrenia spectrum disorder, and 49 persons without a psychiatric disorder completed the Interpersonal Reactivity Index (IRI), Questionnaire of Cognitive and Affective Empathy (QCAE), and Faux Pas as instruments to measure empathy. The Time Use survey was used to measure social functioning. MAN(C)OVA was used to analyse differences between groups on empathy and social functioning, and correlations were calculated between empathy measures and social functioning for each group.Results: The UHR group presented significantly lower levels of self-reported cognitive empathy than the healthy controls, but not compared to patients with SSD, while performance-based cognitive empathy was unimpaired in the UHR group. On the affective measures, we found that people with UHR and patients with SSD had significantly higher levels of self-reported distress in interpersonal settings compared to healthy controls. In the UHR group, perspective-taking was negatively associated with time spent on structured social activities. In the SSD group, we found that structured social activities were positively associated with perspective-taking and negatively associated with personal distress in interactions with others. Lastly, in people without mental illness, social activities were positively associated with performance-based perspective-taking.Conclusion: Impairments in subjective cognitive empathy appear to be present in the UHR phase, suggesting that difficulties in interpreting the thoughts and feelings of others precede the onset of psychotic disorders. This can inform future interventions in the UHR phase.

Time to Refractory Status Defines Subsets of Primary Refractory Diffuse Large B-Cell Lymphoma with Distinct Outcomes

Time to Refractory Status Defines Subsets of Primary Refractory Diffuse Large B-Cell Lymphoma with Distinct Outcomes

Early Relapse Post Autologous Transplantation Is Associated with Very Poor Survival and Identifies an Ultra High Risk Group of Myeloma Patients

Treatment with high dose melphalan (HDM) and autologous stem cell transplantation (ASCT) improves progression free survival (PFS) and overall survival (OS) of myeloma patients and is a standard therapy for eligible patients. Furthermore, the use of maintenance therapy after ASCT is beneficial. However, a subset of patients relapses early after HDM, and there is a paucity of data about their outcomes and characteristics, especially regarding their identification at diagnosis or early in the course of the disease. The aim of the current study was to describe the characteristics, the management and outcomes of patients relapsing within 12 months from HDM.The study included 297 consecutive patients treated in the Department of Clinical Therapeutics, Athens, Greece, which received HDM-ASCT as part of first line therapy from 1995 until June 2016. Median age was 55 years (range 22-67); 38% were ISS-1, 31% ISS-2 and 30% ISS-3. Induction was bortezomib-based in 47%, thalidomide-based in 13%, lenalidomide-based in 6%, high dose dexamethasone-based in 25% and contained both bortezomib and an IMiD in 9%. After ASCT, 35% received consolidation and 30% maintenance.Median follow up for all patients is 5 years, 183 (62%) have relapsed, the median PFS post HDM was 36 months and 43 (13.5%) patients have progressed within <12 months post HDM. In univariate analysis, the baseline LDH ≥250 IU/L (37% vs 15%, p<0.001), eGFR <30 ml/min (22% vs 12%, p=0.055), hypercalcemia (26% vs 16%, p=0.069) and high-risk cytogenetics (available in 138 patients) (39% vs 23%, p=0.084) were associated with early relapse. Response to induction therapy was not predictive of early relapse but less than sCR/CR post HDM (day 100) was associated with early progression (p=0.1). The use of consolidation therapy post HDM was associated with lower rates of early relapses (4% vs 14% for maintenance and 26% for no post-HDM therapy, p<0.001). In multivariate analysis, LDH ≥250 IU/L (HR: 3.4, p=0.01) and hypercalcemia (HR: 3, p=0.006) at diagnosis increased while the use of consolidation reduced the risk of early relapse (HR: 0.23, p=0.012). Due to the limited number of patients with cytogenetics this parameter was not included in the multivariate model.Baseline characteristics that were associated with PFS post HDM included high-risk cytogenetics (HR: 2.1, p=0.003), ISS-3 (HR: 1.4, p=0.03), hemoglobin <10 g/dl (HR: 1.6, p=0.001), hypercalcemia (HR: 1.6, p=0.014) and achievement of sCR/CR after HDM (HR: 0.8 vs VGPR, p=0.18 and HR: 0.67 vs PR, p=0.06). The use of maintenance therapy (HR: 0.54, p=0.01) was also associated with better PFS. In multivariate analysis, the use of maintenance therapy (HR: 0.58, p=0.032) and sCR/CR post HDM (HR: 0.64 vs PR, p=0.06 and HR: 0.9 vs VGPR, p=0.17) were independently associated with PFS. In further analysis, PFS to 2nd line therapy was 14 months for all patients, but only 5 months for those with an early relapse vs 19 months for the other patients (P<0.001). Median PFS2 was 15.5 months for patients with a relapse <12 months post HDM vs 57% at 5 years for the other patients (p<0.001).The 5-years OS is 67%, but, median post HDM OS was 18 months for those with an early relapse vs 71% at 5 years for those with post HDM PFS ≥ 12 months (p<0.001; Figure). In univariate analysis prognostic factors for OS after HDM included high risk cytogenetics (HR: 3, p<0.001), ISS-3 (HR: 2.2, p<0.001), hypercalcemia (HR: 2.8, p<0.001), anemia (HR:1.9, p=0.001), LDH ≥250 IU/L (HR: 1.7, p=0.054) and sCR/CR after HDM (HR: 0.7, p=0.082), use of maintenance (HR: 0.5, p=0.014) or consolidation (HR: 0.61, p=0.017) after HDM. In multivariate analysis PFS post ASCT <12 months (HR: 14, p<0.001) was the most important prognostic factor; other factors included post-HDM sCR/CR (HR: 0.48 vs PR, p=0.021 and HR: 0.54 vs VGPR, p=0.054), hypercalcemia at diagnosis (HR:2.1, p=0.005) but not maintenance (p=0.1) or consolidation therapy (p=0.54) post ASCT.In conclusion, 13% of patients with newly diagnosed MM that receive HDM at first remission relapse within 12 months after ASCT and they have very poor outcomes. These patients should be considered as an ultra high-risk group that urgently needs more effective therapies and innovative approaches through targeted clinical trials. The use of consolidation in patients at high risk for early relapse, such as those with high LDH and hypercalcemia at diagnosis, may reduce early relapses, and maintenance may prolong PFS. [Display omitted] DisclosuresKastritis:Janssen: Honoraria, Research Funding; Gebesis/Celgene: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria. Terpos:Abbvie: Honoraria; BMS: Honoraria; Amgen: Honoraria, Other: SC member, Research Funding; Janssen: Honoraria, Research Funding; Genesis/Celgene: Honoraria, Other: DMC member, Research Funding; Takeda: Honoraria, Other: SC member; GSK: Honoraria. Dimopoulos:Novartis: Consultancy, Honoraria; Genesis Pharma: Research Funding; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology.

Lenalidomide Maintenance Significantly Improves Outcomes Compared to Observation Irrespective of Cytogenetic Risk: Results of the Myeloma XI Trial

Lenalidomide Maintenance Significantly Improves Outcomes Compared to Observation Irrespective of Cytogenetic Risk: Results of the Myeloma XI Trial

Anhedonia in the Psychosis Risk Syndrome: State and Trait Characteristics.

Previous studies reported deficits in pleasure experience in schizophrenia, but little is known about anhedonia in psychosis risk syndrome. Aim of this study was: (1) to assess anhedonia in distinct help-seeking subgroups of young people identified through the Ultra-High Risk (UHR) criteria, (2) to explore its association with functioning and psychopathology in the UHR group, and (3) to monitor longitudinally its stability in UHR individuals along 1-year follow-up period. All participants (78 UHR, 137 with a First Episode Psychosis (FEP), and 95 non-UHR/FEP), aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Beck Depression Inventory-II (BDI-II), the Schizotypal Personality Questionnaire - Brief version (SPQ-B), the Brief O-LIFE questionnaire (BOL), and the World Health Organization Quality of Life - Brief version (WHOQOL-BREF). We adopted two different indexes of anhedonia: i.e. CAARMS "Anhedonia" item 4.3 and BOL "Introvertive Anhedonia" subscale scores. In comparison with non-UHR/FEP, UHR individuals showed higher baseline CAARMS item 4.3 and BOL "Introvertive Anhedonia" subscale scores. No difference in anhedonia scores between UHR and FEP patients was found. After 1-year follow-up period, UHR subjects had a significant decrease in severity exclusively on CAARMS item 4.3 subscore. In the UHR group, CAARMS anhedonia showed significant correlations with functioning deterioration, negative symptoms, and comorbid depression (including suicide ideation), while BOL anhedonia with a poorer self-perceived quality of life and specific schizotypal personality traits (i.e. interpersonal deficits and disorganization). Anhedonia is prominent in the psychosis risk syndrome and its severity is indistinguishable from that of FEP patients.

Social cognition in adolescents at risk for psychosis: A 2-year follow-up study

IntroductionDeficits in social cognition have been reported in people at ultra-high risk (UHR) of psychosis exclusively using socio-cognitive tasks and in adolescent and young adult mixed population.Objectives Aim of this study was (1) to assess subjective experience of social cognition in adolescent help-seekers identified through UHR criteria, (2) to explore its significant correlations with psychopathology and functioning in UHR individuals; and (3) to monitor longitudinally its stability after a 24-month follow-up period.MethodsParticipants [51 UHR, 91 first-episode psychosis (FEP), and 48 non-UHR/FEP patients], aged 13–18 years, completed the comprehensive assessment of at-risk mental states and the GEOPTE scale of social cognition for psychosis.Results In comparison with non-UHR/FEP patients, both UHR and FEP adolescents showed significantly higher GEOPTE total scores. After 12 months of follow-up, UHR individuals had a significant decrease in severity on GEOPTE “Social Cognition” subscore. In the UHR group at baseline, GEOPTE scores had significant positive correlations with general psychopathology, positive and negative dimensions. Across the 2-year follow-up period, social cognition subscores specifically showed more stable associations with general psychopathology and negative symptoms.ConclusionsSocial cognition deficits are prominent in UHR adolescents and similar in severity to those of FEP patients at baseline. However, these impairments decreased over time, presumably together with delivery of targeted, specialized models for early intervention in psychosis.

Development and Analysis of a Weighed Prognostic Model in Newly Diagnosed Multiple Myeloma Patients

Background and Objective: Multiple myeloma (MM) is characterized with significant cytogenetic changes and complex tumor microenvironment, thus patient survival is extremely heterogeneous. Various disease-related or patient-related factors affect the prognosis of patients. This study tried to analyze the prognostic indicators of patients with newly-treated MM, especially explored the prognosis of multiple cytogenetic abnormalities and the ratio of lymphocytes to monocytes (LMR). Additionally, we established a comprehensive prognostic model to help determine the patient prognosis. Methods: After screening, 603 patients of untreated MM from January 2008 to June 2017, with complete baseline indicators were enrolled into the study. By univariate and multivariate Cox analysis, risk factors related to the prognosis of patients were evaluated, and a weighted prognosis model was established to compare the survival differences of patients in each risk stratification. Result: Optimal thresholds of ALC, LWR, NLR and LMR were determined by ROC curve and Youdex index: ALC = 1.415, LWR = 0.325, NLR = 1.935, LMR = 2.95. Survival analysis showed that patients with LMR ≤ 2.95, ALC ≥ 1.415 and LWR ≥ 0.325 had significantly better survival compared with their respective control groups. Cox multivariate analysis showed that among the four indicators, only LMR≤2.95 was an independent adverse prognostic factor for overall survival (OS)(Figure 1A). 17p deletion, 1q21 amplification, t (4; 14) / t (14; 16) were define as high-risk cytogenetic abnormalities (HRA). Of the 603 patients, about 60% were associated with at least one high-risk cytogenetic event. Among them, the occurrence of cumulative 0, 1, 2, and 3 HRA were 39.6% (239/603), 42.5% (256/603), 16.6% (100/603), and 1.3% (8/603), respectively. There was no significant difference in survival among patients with same number of HRAs. The median OS of patients with 0, 1 and ≥ 2 HRA were not reached, 62.1 months (95% CI, 49.3-74.9) and 30.4 months (95% CI, 24.5-36.3), respectively (p &amp;lt;0.001)(Figure 1B).Final Cox regression model showed that age 65 ~ 74 (HR=1.77, 95%CI, 1.24-2.51, p=0.001), age ≥75 (HR=2.46, 95%CI, 1.69-3.58, p &amp;lt; 0.001), LDH≥247 U/L (HR =1.65, 95%CI, 1.07-2.51, p=0.023), ISS stage III (HR=1.76, 95%CI, 1.24-2.50, p=0.002), LMR≤2.95 (HR=1.53, 95%CI, 1.08-2.18, p=0.017), 1 HRA (HR=1.87, 95%CI, 1.27-2.75, p=0.002) and ≥2 HRA (HR=3.48, 95%CI, 2.22-5.45, p&amp;lt;0.001) are independent adverse prognostic factors for OS. Then weighted risk factors were summed to establish a comprehensive prognosis model, with a total score range of 0-6 points. Accordingly, the whole cohort was divided into low risk (0-1 points, 45.4%), intermediate risk (2 points, 27.9%), high risk (3 points, 19.2%) and ultra-high risk (4-6 points, 7.5 %) groups. The median OS of the four risk groups were 85.8 months (67.1-104.5), 49.0 months (44.7-53.3), 35.4 months (31.3-39.5), and 23.2 months (18.8-27.6), respectively (p&amp;lt;0.001). The C-statistics of this prognostic model is 0.68 (95% CI, 0.64-0.71), which is significantly better than the D-S stage (C-statistics = 0.52, 95% CI, 0.50-0.55, p &amp;lt;0.001), ISS (C-statistics = 0.60, 95% CI, 0.57-0.64, p &amp;lt;0.001) and R-ISS stage (C-statistics = 0.60, 95% CI, 0.57-0.63, p &amp;lt;0.001). Bootstrap resampling and calibration curve showed that the model has an accurate predictive effect on both short-term and long-term prognosis of patients(Figure 1C). Conclusion: In our analysis, ALC, LWR, LMR were associated with poor prognosis in NDMM patients, while NLR had no significant prognostic significance. Among the four indicators, LMR≤2.95 was the only independent prognostic factor. In NDMM patients, survival of patients with the same number of high-risk cytogenetic abnormalities were comparable with each other, regardless of whichever combination of HRA. Higher number of high-risk cytogenetic abnormalities were associated with worse prognosis. Cox multivariate analysis showed that, old age (65-74 years old, ≥75 years old), increased LDH (≥247 U/L), decreased LMR (≤2.95), ISS III, 1 HRA and ≥ 2 HRA were independent adverse prognostic factors that affect the OS of MM patients. 4. A comprehensive weighted prognostic model was established with the above factors, which was proved to effectively distinguish different prognosis of patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

Interview and questionnaire assessment of cognitive impairment in subjects at ultra-high risk for psychosis: Associations with cognitive test performance, psychosocial functioning, and positive symptoms

Impaired cognitive test performance is well-documented in subjects at ultra-high risk (UHR) for psychosis. However, assessment of cognitive deficits as manifested in real life is a neglected area of UHR research that may add to the understanding of cognitive impairment and its relationship with psychosocial functioning and positive symptomatology. This study applied the interview-based Schizophrenia Cognition Rating Scale (SCoRS) and the questionnaire-based Behavior Rating Inventory of Executive Function – Adult Version (BRIEF-A) in a cross-sectional sample of 39 UHR subjects and 50 healthy controls. Cognitive test performance, psychosocial functioning, and positive symptoms were also assessed. The UHR subjects demonstrated significant cognitive impairment, with large effect sizes for the SCoRS and BRIEF-A composite outcome variables (rs = -0.67 to -0.80) and a neurocognitive composite score (d = -0.97). Within the UHR group, several significant associations between worse cognitive ratings and worse cognitive test performance (rs = -0.210 to -0.343), poorer psychosocial functioning (rs = -0.058 to -0.728), and worse positive symptoms (rs= 0.415 to 0.478) were found. Worse cognitive test performance showed significant associations with more pronounced positive symptoms (rs = -0.299 to -0.457). Interview and questionnaire assessment may hold promise for supplementing traditional performance-based cognitive assessment in identifying treatment targets in the UHR population.

Efficacy of psychological interventions in young individuals at ultra-high risk for psychosis: A naturalistic study.

Early detection and intervention in individuals at risk for developing psychosis have become a priority for many clinical services around the world. Limited naturalistic evidence is available on whether detection and intervention for ultra-high risk (UHR) is effective by means of reducing psychosis risk and improving functioning. We compared functioning scores over 5.9 (±7.7) months of time between UHR individuals (n=61) and help-seeking adolescents without a specific UHR profile (general adolescent help-seeking population [HSP]; n=82) aged 12 to 25 years receiving psychological interventions at a specialized UHR service in the Netherlands. Attenuated psychotic symptoms (APS) were evaluated over time within the UHR group. In addition, the impact of duration of treatment, <7 sessions, 8 to 21 sessions and >20 sessions, as well as treatment type, that is, cognitive behavioural therapy (CBT) and CBT + add on treatment, were evaluated. Both UHR and HSP showed an increase in functioning over time (P< .001), with no difference between these groups. The UHR group showed a reduction of APS over time (P< .001). More than 20 treatment sessions was more effective than 1 to 6 treatment sessions (P< .01, partial eta squared=.08) and CBT was equally effective as CBT-add on in improving functioning. The findings of this study suggest that psychological treatment is just as effective in improving functioning in UHR as in HSP. Moreover, it decreases APS in UHR. Improvement in functioning is not affected by treatment type, but positively affected by the duration of treatment.

Cognitive remediation plus standard treatment versus standard treatment alone for individuals at ultra-high risk of developing psychosis: Results of the FOCUS randomised clinical trial

BackgroundIndividuals at ultra-high risk (UHR) for psychosis have significant cognitive deficits that can impede functional recovery. Applying cognitive remediation (CR) before the onset of frank psychosis may improve the cognitive and functional prognosis of UHR individuals, however, little is known about the feasibility and efficacy of CR for this population. MethodsIn this randomised, clinical trial 146 individuals at UHR for psychosis aged 18–40 years were randomly assigned to treatment as usual (TAU) or TAU plus cognitive remediation. The CR targeted neurocognitive and social cognitive remediation. Assessments were carried out at 6- and 12-months post baseline. ResultsA total of 73 UHR individuals were assigned to TAU and 73 assigned to TAU + cognitive remediation. Compared to the control group, cognitive remediation did not result in significant improvement on the primary outcome; the Brief Assessment of Cognition in Schizophrenia composite score at 6-month follow-up (b = −0.125, 95%CI: −0.23 to 0.172, p = 0.41). Nor did the intervention improve secondary outcomes in clinical symptoms or functioning. Exploratory analyses found emotion recognition latencies to be significantly more reduced in the intervention group at 6-months. At 12-months, the intervention group exhibited significantly better performance on two measures of executive function and visual memory. ConclusionThe 20-session treatment protocol was not well received in the UHR group, and unsurprisingly global measures did not improve. The benefit found in isolated neuro- and social cognitive measures after even a few sessions points to a potential for cognitive malleability if people can be engaged sufficiently to practice the skills.Trial registration ClinicalTrial.gov identifier: NCT02098408.

Self-esteem in individuals at ultra-high risk for psychosis: A systematic review and meta-analysis.

Low self-esteem (LSE) has been reported among individuals with psychosis and is hypothesized to act as a risk and maintenance factor for the disorder. However, the extent to which LSE also characterizes individuals deemed at ultra-high risk (UHR) for psychosis (who present features consistent with the prodromal phase of illness), has yet to be quantified using meta-analysis. This is important given that LSE is a potentially modifiable target for early intervention services aiming to reduce the risk of psychosis transition in this population. We searched Medline, Embase, PsycINFO and Web of Science Core Collection for studies examining self-esteem in UHR and healthy individuals. Random-effects models were used to examine group differences in self-esteem (Hedges'g) with exploratory meta-regression analyses employed to investigate the effect of study characteristics (mean age of UHR group, the proportion of male participants in the UHR group and study quality) on standardized mean differences. Six studies were eligible for inclusion. Significant differences in self-esteem were observed, with individuals at UHR showing reduced self-esteem relative to healthy controls (g= -1.33 [-1.73 to -0.94] P< .001).However, there was evidence of substantial heterogeneity (I2 = 75%). Exploratory meta-regression analyses indicated a significant effect of the mean age of the UHR group on effect sizes (B= -0.26, P= .02). UHR youth present with lower levels of self-esteem than healthy individuals, a difference that appears to be more pronounced with advancing age. We discuss clinical implications and provide recommendations for future studies.

Subjective experience of social cognition in young people at Ultra-High Risk of psychosis: a 2-year longitudinal study

Purpose Impairments in SC have been reported in people at Ultra-High Risk (UHR) of psychosis exclusively using neurocognitive tasks. The aims of this study are (1) to assess subjective experience of SC in adolescent and young adult community help-seekers identified through UHR criteria, (2) to explore significant associations of SC with psychopathology and functioning in UHR individuals; and (3) to monitor longitudinally the SC stability after a 2-year follow-up period. Methods: Participants (97 UHR, 141 First-Episode Psychosis [FEP], and 98 non-UHR/FEP), aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the GEOPTE scale of social cognition for psychosis. Within the UHR group, a multiple linear regression analysis (with GEOPTE scores as independent variables and CAARMS dimension subscores and treatment measures as dependent variables) was also performed across the 2-year longitudinal design. Results: In comparison with non-UHR/FEP, both UHR and FEP subjects showed significantly higher GEOPTE scores. Both after 12 and 24 months of follow-up, UHR individuals had a significant decrease in severity on GEOPTE SC subscore. In the UHR group, GEOPTE scores showed significant positive correlations with general psychopathology, positive and negative symptoms. Regression analysis showed a significant contribution of SC in predicting baseline social isolation, impaired role functioning, and general psychopathology. After 1 year of follow-up, improvement in SC was predicted by the number of psychotherapy sessions and lower doses of antipsychotics. Conclusions: SC deficits are prominent in UHR individuals and are similar in severity to those of FEP patients. However, they tend to decrease over time along with the delivery of targeted, specialized interventions for early psychosis.

Mismatch Negativity Predicts Remission and Neurocognitive Function in Individuals at Ultra-High Risk for Psychosis.

BackgroundIn the early intervention in psychosis, ultra-high risk (UHR) criteria have been used to identify individuals who are prone to develop psychosis. Although the transition rate to psychosis in individuals at UHR is 10% to 30% within several years, some individuals at UHR present with poor prognoses even without transition occurring. Therefore, it is important to identify biomarkers for predicting the prognosis of individuals at UHR, regardless of transition. We investigated whether mismatch negativity (MMN) in response to both duration deviant stimuli (dMMN) and frequency deviant stimuli (fMMN) could predict prognosis, including remission and neurocognitive function in individuals at UHR.Materials and MethodsIndividuals at UHR (n = 24) and healthy controls (HC; n = 18) participated in this study. In an auditory oddball paradigm, both dMMN and fMMN were measured at baseline. Remission and neurocognitive function after > 180 days were examined in the UHR group. Remission from UHR was defined as functional and symptomatic improvement using the Global Assessment of Functioning (GAF) score and Scale of Prodromal Symptoms (SOPS) positive subscales. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia (BACS). We examined differences in MMN amplitude at baseline between those who achieved remission (remitters) and those who did not (non-remitters). Multiple regression analyses were performed to identify predictors for functioning, positive symptoms, and neurocognitive function.ResultsCompared with the HC group, the UHR group had a significantly attenuated dMMN amplitude (p = 0.003). In the UHR group, GAF scores significantly improved during the follow-up period (mean value 47.1 to 55.5, p = 0.004). The dMMN amplitude at baseline was significantly larger in the remitter (n = 6) than in the non-remitter group (n = 18) (p = 0.039). The total SOPS positive subscale scores and fMMN amplitude at baseline could predict BACS attention subscore at the follow-up point (SOPS positive subscales, p = 0.030; fMMN, p = 0.041).ConclusionOur findings indicate that dMMN and fMMN predicted remission and neurocognitive function, respectively, in individuals at UHR, which suggests that there are both promising biomarker candidates for predicting prognosis in individuals at UHR.

Preliminary study of PD-1 inhibitor in the treatment of drug-resistant recurrent gestational trophoblastic neoplasia

Objective: To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN). Methods: Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed. Results: (1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment. Conclusions: PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

S112. ELUCIDATING THE CHRONOLOGY OF FLUCTUATIONS IN BASIC SYMPTOMS, EARLY SIGNS AND PSYCHOTIC SYMPTOMS IN ESTABLISHED PSYCHOSIS USING REPEATED MEASURES DATA GATHERED USING A SMARTPHONE APP

BackgroundPsychosis relapses are common, have profound adverse consequences for patients, and are costly to health services. ‘Early signs’ (e.g. anxiety; insomnia) have been used to predict relapse, in the hope of prevention or mitigation, with moderate sensitivity and specificity. Recent studies have provided preliminary prospective evidence that assessing ‘basic symptoms’ (e.g. vivid colour vision; disturbances in expressive speech) in addition to conventional early signs improves relapse prediction.Basic symptoms are assumed to be one of the earliest, most basic subjective expressions of the underlying neurobiological disruption preceding the development of psychosis. There is some empirical evidence from ultra-high risk groups suggesting that basic symptoms do indeed emerge prior to other risk indicators during the prodromal period. However, no studies to date have examined the relative timing of increases in basic symptoms, conventional early signs and psychotic symptoms in individuals with established psychosis.In the current study, we used time-lagged, repeated measures, prospective data to test whether increased basic symptoms would precede increased conventional early signs, and in turn increased psychotic symptoms.MethodsIndividuals who had experienced a relapse of psychosis within the past year (n=18) were asked to use a smartphone app (‘ExPRESS’) weekly for six months to report early signs, basic symptoms and psychotic symptoms. Participants completed 65% of app assessments over the 6 month follow-up period, providing >200 observations in total. These data were analyzed using mixed effects models to account for clustering within individuals and to allow for missing data.ResultsApp items showed high concurrent validity with researcher-rated psychotic symptoms (ρ range 0.80 to 0.87, p<0.001) and basic symptoms (ICC=0.76, p<0.001) over six months. The results of the mixed effects analyses described above will be presented in full, and their theoretical and clinical implications will be discussed.DiscussionWe anticipate that the findings of this study will be of theoretical interest. Within the socio-developmental-cognitive model (Howes & Murray, 2014), it would be logical to equate basic symptoms with the initial ‘anomalous experiences’ that are proposed to occur as a result of a disrupted dopamine system. Conventional early signs may then either occur later in the deterioration process laid out in the model or, as a heterogeneous group, may relate to more than one stage of the process. The results of the current study may help to elucidate the place of basic symptoms and conventional early signs within the socio-developmental-cognitive model. The findings may also lend support to the idea that basic symptoms are dopaminergic in origin.