Adverse Disease Features Research Articles

Abstract PO5-09-06: Outcomes of breast cancer in a minority-enriched population treated at a large safety-net system: Is site of care a predictor of poor outcomes?

Abstract Background: Breast cancer outcomes in the United States continue to improve, but sociodemographic disparities remain prevalent and impact care delivery and outcomes in vulnerable populations. Safety-net health systems are intended to address inequities by providing access to care for the uninsured/underinsured. Care delivery in a safety-net setting is often inherently complicated by limited resources at these institutions. Here, we present the overall survival (OS) data of breast cancer patients treated at a large safety-net system, compared to the national average. Methods: Parkland Health (PH) is the safety-net system for Dallas County and is affiliated with the University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center (NCI-CCC). Electronic medical records of patients diagnosed with invasive breast cancer between 2018 to 2020 at PH were reviewed and data on demographics, treatment, and outcomes were collected. Categorical data was summarized with counts and percentages and continuous data was summarized with median and interquartile range. Statistical comparisons used Chi-square test for categorical data and rank sum test for continuous data with a significance level of 0.05. Survival data was analyzed using Cox proportional hazard model. Data from the National Cancer Database (NCDB) for the same period was used for comparison. Results: Of the 657 patients included in the study, the majority (82.5%) belonged to racial and ethnic minorities (Hispanic 50.2%; Black 32.3%). Compared to the NCDB, PH patients were more often uninsured (67% vs 1.6%) or enrolled on Medicaid (14.5% vs 6.9%), and less often on Medicare (8.5% v. 43%) (p< 0.01). Triple negative breast cancer (TNBC) phenotype and late-stage diagnosis (stage III/IV) rates were higher at PH compared to NCDB (TNBC 22.8% vs 10.7%, p< 0.01; late stage 30.6% vs 13.2%, p< 0.01). At a median follow up of 33 (range 24-43) months in PH and 28 (range 21-36) months in NCDB, the unadjusted OS for the PH population was 86.3% vs 92.6% for the NCDB population (p < 0.01). Within the PH population, Black race, higher stage, and TNBC were associated with decreased OS. There was a significant interaction between Black race and TNBC. When combining all patients (PH+NCDB), site of care (PH) was associated with a higher risk of death from breast cancer (HR 1.467, 95% CI 1.192-1.805, p< 0.0005), however, multivariate analysis did not show a significant difference based on site of care. Factors associated with a significantly increased risk of death in this multivariate analysis (corrected for interaction between Black race and TNBC phenotype) included age, late-stage diagnosis, TNBC, Black race, and uninsured status (Table 1). Conclusions: Breast cancer patients treated at PH were more likely to have adverse disease characteristics compared to the NCDB population. When accounting for these risk factors in multivariate analysis, patients treated at PH had similar outcomes compared to the national average. Our findings reinforce the critical role of safety-net systems in promoting health equity and eliminating disparities. Table 1 Citation Format: Sarah Kashanian, Shifa Kanjwal, L. Steven Brown, Andrea Semlow, Mary Hodges, Robyn Cobb, Brad Walsh, Umber Dickerson, Navid Sadeghi. Outcomes of breast cancer in a minority-enriched population treated at a large safety-net system: Is site of care a predictor of poor outcomes? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-06.

Abstract B075: Developing a population-based study of South Asian American breast cancer survivors in New Jersey

Abstract Background: South Asian Americans (SAA) are the largest Asian American subgroup in New Jersey (NJ). Breast cancer is a growing health concern among SAA women, who tend to have young age at onset, regional or distant stage disease, and triple negative subtype. However, there is limited health and genetic data from these women to gain fruitful insights into the drivers of their adverse disease characteristics. Purpose: To address the breast cancer-related data gap among SAA women, we recently launched the Cancer Analytics and South Asian Health – Breast Cancer (CANSAH-BC) Study at Rutgers University. This ongoing study is designed to evaluate the impact of lifestyle, reproductive, medical, and germline genetic factors on tumor characteristics and health-related quality-of-life among SAA women. Here, we describe our recruitment and data collection methods, and summarize the characteristics of participants who have completed the study. Methods: We are partnering with the NJ State Cancer Registry (NJSCR) to recruit SAA breast cancer survivors. Eligible women are those identified as SAA by NJSCR, diagnosed with malignant breast cancer in 2018-2020, and age 18-80 years at diagnosis. We are using a validated structured questionnaire to collect data on lifestyle, reproductive, family history, and medical factors, breast cancer treatment history, and health-related quality of life. We are sending saliva sampling kits with a return postage pre-paid envelope to participants, who return their saliva samples to be stored for future genetic studies. To demonstrate feasibility of recruitment and data collection, we are conducting the pilot phase of the CANSAH-BC study with a target sample size of 100 participants. We started the pilot phase in English language and are currently expanding to other South Asian languages. Results: As of May 2023, NJSCR identified 375 eligible women, among which 119 (32%, 95% confidence interval (CI): 27.0% - 36.7%) agreed to participate. Initial contact by NJSCR began in September 2022 and is continuing. Data collection began in December 2022 and has been completed from 26 (22%) of 119 women. Data collection from the remaining participants is underway. Of the 26 participants, 25 (96%, 95% CI: 80.4% - 99.9%) provided a saliva sample. The average age at diagnosis of breast cancer in the 26 participants is 50.9 (SD = 11.8) years, 10 (38%) have at least one family member with breast cancer, 23 (88%) were born in a South Asian country and moved to the U.S. at an average age of 29 years, 7 (27%) have a history of hypertension, and 21 (81%) are either overweight or obese. Conclusion: Our preliminary study showed a relatively high participation rate in the saliva sample component of the CANSAH-BC study. The data suggest evidence of family history of breast cancer, hypertension, overweight or obesity among SAA women with a high percentage first-generation immigrants. This ongoing study represents a unique resource to better understand the drivers of adverse prognosis among South Asian American women diagnosed with breast cancer. Citation Format: Tina Dharamdasani, Prachi Trivedi, Nur Zeinomar, Bo Qin, Lisa Paddock, Antoinette Stroup, Gregory Riedlinger, Shridar Ganesan, Hao Liu, Anita Y. Kinney, Elisa V. Bandera, Jaya M. Satagopan. Developing a population-based study of South Asian American breast cancer survivors in New Jersey [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B075.

Pivekimab Sunirine (PVEK, IMGN632), a CD123-Targeting Antibody-Drug Conjugate, in Combination with Azacitidine and Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia

Background In unfit patients (pts) with newly diagnosed (ND) AML, long-term survival remains short (mOS 14.7 months) despite improved responses (CR 37% and CR/CRi 66%) with azacitidine (AZA) and venetoclax (VEN) (VIALE-A, DiNardo NEJM 2020). In a pooled analysis of AZA-VEN in ND AML pts with poor risk cytogenetics the response rates were higher in TP53wt pts (CR/CRi 70%) compared with TP53mut pts (CR/CRi 41%) (Pollyea Clin Cancer Res 2022). The measurable residual disease (MRD)-negative rate was 41% in AZA-VEN treated pts in VIALE-A which was associated with improved survival (Pratz JCO 2022). Pivekimab sunirine (PVEK, IMGN632) is a first-in-class antibody-drug conjugate (ADC) comprising a high-affinity CD123 antibody, cleavable linker, and an indolinobenzodiazepine pseudodimer (IGN) payload. The novel IGN payload alkylates DNA and causes single strand breaks without crosslinking (Kovtun Blood Adv 2018). Methods This is an ongoing, open-label, multicenter, Phase 1b/2 study of PVEK in combination with AZA +VEN in adults with ND CD123-positive AML (any CD123+ expression by local flow cytometry or IHC). Pts received the recommended phase 2 dose of PVEK 0.045 mg/kg IV on D7 + AZA 75 mg/m 2 SC or IV daily on D1-7 + VEN up to 400 mg PO daily for 14 to 28 days (based on cohort assignment) in a 28-day cycle. Bone marrow assessment was performed at D14 (cohort 1) or D21 (cohort 2) of cycle 1 to determine VEN duration. The primary endpoints are composite CR rate (CCR [CR+CRh+CRp+CRi]), MRD rate (assessed centrally [Hematologics, Inc.] by flow cytometry; <0.1% defined as negative) and duration of remission. Key secondary endpoints are safety, pharmacokinetics and immunogenicity. Responses were determined using ELN 2017 criteria (with the addition of CRh) and a 14-day post-marrow count recovery window. Results As of July 17, 2023, data is available for 50 ND pts (n=25 per cohort) treated with PVEK+AZA+VEN and are aggregately reported here. The median age was 74 years (range, 46-83), 42% were ≥ 75 years old, 26% had secondary AML, 64% were ELN 2017 adverse risk, and 38% had a TP53mut. The most common non-hematologic treatment-emergent adverse events (TEAE) (all grades [grade 3+]) seen in > 20% of all pts were febrile neutropenia (44% [38%]), constipation (42% [2%]), peripheral edema (36% [4%]), diarrhea (36% [2%]), hypophosphatemia (32% [0%], nausea (28% [4%]), and hypokalemia (24% [2%]). No veno-occlusive disease (VOD) events were reported. In responders, the median time to achieve absolute neutrophil count ≥500/µL and platelet count ≥50,000/µL was 35.5 days (range, 20-55) and 22 days (range, 20-55), respectively. The median post-remission cycle delay (beyond cycle day 28) was 14 days. Two pts discontinued PVEK due to a TEAE (edema; marrow aplasia). The 60-day mortality was 4%. In the ITT population (N=50) the CR rate was 52% (26/50), and the CCR rate was 66% (33/50). In pts ≥ 75 years old, the CCR rate was 76% (16/21). In pts known to be TP53wt, both the CR and CCR rate was 88% (22/25). Additional response subsets in Table 1. Twenty-one pts received 9-14 days of VEN, 9 pts received 15-21 days of VEN and 20 pts received ≥ 22 days of VEN in cycle 1; of those who received ≤ 14 days of VEN the CR rate was 71% (15/21) and the CCR rate was 76% (16/21). Of the 26 pts who achieved CCR and had an MRD-evaluable sample, 73% (19/26) achieved MRD negativity (CCR MRD-, <0.1% residual blasts); notably all had undetectable MRD levels (lower level of detection is 0.02%). MRD-negativity was achieved rapidly with a median of 1.7 months (range, 0.8-4.5). CCR MRD- rates were high across major molecular subsets, including FLT3 (ITD/TKD) at 100% (7/7), IDH1/2 at 89% (8/9), and NPM1 at 89% (8/9), as well as ELN risk groups (intermediate 80% [8/10]; adverse 64% [9/14]). Conclusion With a manageable safety profile in pts with ND AML, the PVEK+AZA+VEN triplet demonstrated anti-leukemia activity with robust CR rates and early MRD negative responses in a cohort enriched for adverse disease characteristics (64% ELN adverse risk; 38% TP53mut). Encouraging CCR MRD- rates were observed across cytogenetic/molecular subsets, and the majority of responding pts achieved early and deep remissions, which may translate to improved clinical outcomes. The regimen was well tolerated with no new safety signals, and the addition of PVEK to the AZA-VEN backbone did not appear to meaningfully prolong count recovery.

The Absolute Monocyte Count at Diagnosis Affects Prognosis in Myelodysplastic Syndromes Independently of the IPSS-R Risk Score.

The absolute monocyte count (AMC) is associated with mortality in a variety of medical conditions. Its prognostic impact in myelodysplastic syndromes (MDSs) is less well studied. Therefore, we investigated its potential prognostic value in a cohort from the Düsseldorf MDS registry in relationship to the revised international prognostic scoring system (IPSS-R). An AMC below the population's median (<0.2 × 109/L) was associated with several adverse disease features such as lower haemoglobin levels, lower count of neutrophils and platelets, and a higher percentage of blasts in the bone marrow. MDS patients with an AMC < 0.2 × 109/L had a significantly higher risk of progression into acute myeloid leukemia (AML). In a univariate, proportional hazards model the effect of the AMC as a continuous variable was modelled via p-splines. We found a U-shaped effect with the lowest hazard around 0.3 × 109/L. Accordingly, an AMC within the last quartile of the population (0.4 × 109/L) was associated with a reduced overall survival independently of IPSS-R, but not with the risk of secondary AML. Considering monocytopenia as a risk factor for AML progression in MDS may provide an additional argument for allogeneic transplantation or the use of hypomethylating agents in patients who are not clear candidates for those treatments according to current prognostic scoring systems and/or recommendations. Further studies are needed to assess the prognostic impact of the AMC in the context of prognostic scoring systems, considering the molecular risk profile, and to identify the mechanisms responsible for the higher mortality in MDS patients with a subtle monocytosis.

Taxonomic reclassification of Kaposi Sarcoma identifies disease entities with distinct immunopathogenesis

BackgroundThe taxonomy of Kaposi Sarcoma (KS) is based on a classification system focused on the description of clinicopathological features of KS in geographically and clinically diverse populations. The classification includes classic, endemic, epidemic/HIV associated and iatrogenic KS, and KS in men who have sex with men (MSM). We assessed the medical relevance of the current classification of KS and sought clinically useful improvements in KS taxonomy.MethodsWe reviewed the demographic and clinicopathological features of 676 patients with KS, who were referred to the national centre for HIV oncology at Chelsea Westminster hospital between 2000 and 2021.ResultsDemographic differences between the different subtypes of KS exist as tautological findings of the current classification system. However, no definitive differences in clinicopathological, virological or immunological parameters at presentation could be demonstrated between the classic, endemic or MSM KS patients. Reclassifying patients as either immunosuppressed or non-immunosuppressed, showed that the immunosuppressed group had a significantly higher proportion of adverse disease features at presentation including visceral disease and extensive oral involvement, classified together as advanced disease (chi2 P = 0.0012*) and disseminated skin involvement (chi2 P < 0.0001*). Immunosuppressed patients had lower CD4 counts, higher CD8 counts and a trend towards higher HHV8 levels compared to non-immunosuppressed patients, however overall survival and disease specific (KS) survival was similar across groups.ConclusionThe current system of KS classification does not reflect meaningful differences in clinicopathological presentation or disease pathogenesis. Reclassification of patients based on the presence or absence of immunosuppression is a more clinically meaningful system that may influence therapeutic approaches to KS.

IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.

Is Active Surveillance an Option for the Management of Men with Low-grade Prostate Cancer and a Positive Family History? Results from a Large, Single-institution Series

BackgroundFamily history (FH) of prostate cancer (PCa) is associated with an increased risk of PCa and adverse disease features. However, whether patients with localized PCa and FH could be considered for active surveillance (AS) remains controversial. ObjectiveTo assess the association between FH and reclassification of AS candidates, and to define predictors of adverse outcomes in men with positive FH. Design, setting, and participantsOverall, 656 patients with grade group (GG) 1 PCa included in an AS protocol at a single institution were identified. Outcome measurements and statistical analysisKaplan-Meier analyses assessed the time to reclassification (GG ≥2 and GG ≥3 at follow-up biopsies) overall and according to FH status. Multivariable Cox regression tested the impact of FH on reclassification and identified the predictors among men with FH. Men treated with delayed radical prostatectomy (n = 197) or external-beam radiation therapy (n = 64) were identified, and the impact of FH on oncologic outcomes was assessed. Results and limitationsOverall, 119 men (18%) had FH. The median follow-up was 54 mo (interquartile range 29–84 mo), and 264 patients experienced reclassification. The 5-yr reclassification-free survival rate was 39% versus 57% for FH versus no FH (p = 0.006), and FH was associated with reclassification to GG ≥2 (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.19–2.15, p = 0.002). In men with FH, the strongest predictors of reclassification were prostate-specific antigen (PSA) density (PSAD), high-volume GG 1 (≥33% of cores involved or ≥50% of any core involved), and suspicious magnetic resonance imaging (MRI) of the prostate (HRs 2.87, 3.04, and 3.87, respectively; all p < 0.05). No association between FH, adverse pathologic features, and biochemical recurrence was observed (all p > 0.05). ConclusionsPatients with FH on AS are at an increased risk of reclassification. Negative MRI, low disease volume, and low PSAD identify men with FH and a low risk of reclassification. Nonetheless, sample size and wide CIs entail caution in drawing conclusions based on these results. Patient summaryWe tested the impact of family history in men on active surveillance for localized prostate cancer. A significant risk of reclassification, but not adverse oncologic outcomes after deferred treatment, prompts the need for cautious discussion with these patients, without precluding initial expectant management.

Real World Data on Unique Challenges and Outcomes of Older Patients with AML from Resource Limited Settings: Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC)

Despite significant advances in the treatment of acute myeloid leukemia (AML), outcomes in older patients continue to be suboptimal, due to a combination of adverse disease characteristics and increasing prevalence of co-morbidities. This challenge is further magnified in resource-limited settings where logistical and financial barriers often preclude effective therapy. In addition, a significant number of patients do not undergo any evaluation after diagnosis, resulting in very little real-world data on treatment outcomes in this cohort. We present data on epidemiology and treatment patterns in older patients with AML from the Indian Acute Leukemia Research Database [INwARD] established by Hematology Cancer Consortium (HCC). Retrospective data from 17 centres was collected to include patients older than 55 years diagnosed between January 2018 and April 2021. A lower age cut off of 55 years was used based on previous data indicating adverse physiologic characteristics comparable to a 65 year old individual in the West. No exclusion criteria were specified. The primary objectives were to ascertain the proportion of patients receiving therapy and one-year overall survival among treated patients. Patient status was assessed as on March 31, 2022. A total of 733 patients (M:F=1.48) were included in this study, of which only 339 (46%) patients underwent further evaluation and treatment. The most common reasons for not initiating treatment were to begin evaluation at another centre (37%) and financial constraints(13%). Among treated patients, the median age at diagnosis was 63 years (IQR, 59-69), with 130 (40.2%) having an ECOG performance score ≥ 2 and 203 (60.4%) having at least one comorbidity. No differences in baseline attributes were noted among treated or untreated patients.(Table 1) Of the 339 patients who received treatment, initial therapy comprised hypomethylating agents (HMA) in 247 (72.8%) patients, standard or modified 7+3 regimen in 64 (18.8%) and other intensive regimens in 2 (0.59%) patients. Infections requiring treatment were diagnosed in 117 (40.3%) patients, with 36 (13.79%) requiring intensive care. A second induction was required in 26 patients, of which 5(19%) received intensive chemotherapy and 8 (30%) received HMA. Early mortality (within 60 days of diagnosis) was noted in 58(20.1%) out of 288 evaluable patients at this time point. Poor performance status baseline was significantly associated with early mortality(p=0.015) with no effect of age or associated co-morbidities. Among patients who died within 60 days, a significantly higher white cell count was observed at baseline (median, 20310 vs 7200/mm3,p=0.005). Complete remission (CR) was achieved in 24(36%) patients after intensive chemotherapy. Among 146(59%) evaluable patients receiving HMA, 62(42%) achieved CR at any time point after therapy. The probability of achieving CR significantly decreased with increasing age (p=0.037). Allogeneic stem cell transplant was utilized for only 11 (3.2%) patients in the treated cohort. After a median follow up of 5 months (IQR 1.4 to 14.6 months), 102 (32.2%) patients were lost to follow up and only 72 (26%) had completed treatment. For survival analysis, patients lost to follow up were considered dead at the date of last follow up. At the end of one year, probability of survival was 32.9%, (Figure 1) with the median overall survival being 190 days (95% CI, 143 to 236) in the treated cohort. Among 145 patients with available data, the most common cause of death was progressive disease (52%), followed by infectious complications (29%). Conclusions Our data highlights dual challenges of low rates of treatment initiation and significant treatment discontinuation within one year in patients older than 55 years of age with AML in India. Poor disease biology is also highlighted by low rates of CR irrespective of initial therapy and low probability of survival at one year. Financial challenges emerge as major modifiable factors leading to incomplete treatment. This large registry dataset indicates the need for more effective, affordable and safer treatment options for this group of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mutations of 1p genes do not consistently abrogate tumor suppressor functions in 1p-intact neuroblastoma

BackgroundDeletion of 1p is associated with poor prognosis in neuroblastoma, however selected 1p-intact patients still experience poor outcomes. Since mutations of 1p genes may mimic the deleterious effects of chromosomal loss, we studied the incidence, spectrum and effects of mutational variants in 1p-intact neuroblastoma.MethodsWe characterized the 1p status of 325 neuroblastoma patients, and correlated the mutational status of 1p tumor suppressors and neuroblastoma candidate genes with survival outcomes among 100 1p-intact cases, then performed functional validation of selected novel variants of 1p36 genes identified from our patient cohort.ResultsAmong patients with adverse disease characteristics, those who additionally had 1p deletion had significantly worse overall survival. Among 100 tumor-normal pairs sequenced, somatic mutations of 1p tumor suppressors KIF1Bβ and CHD5 were most frequent (2%) after ALK and ATRX (8%), and BARD1 (3%). Mutations of neuroblastoma candidate genes were associated with other synchronous mutations and concurrent 11q deletion (P = 0.045). In total, 24 of 38 variants identified were novel and predicted to be deleterious or pathogenic. Functional validation identified novel KIF1Bβ I1355M variant as a gain-of-function mutation with increased expression and tumor suppressive activity, correlating with indolent clinical behavior; another novel variant CHD5 E43Q was a loss-of-function mutation with decreased expression and increased long-term cell viability, corresponding with aggressive disease characteristics.ConclusionsOur study showed that chromosome 1 gene mutations occurred frequently in 1p-intact neuroblastoma, but may not consistently abrogate the function of bonafide 1p tumor suppressors. These findings may augment the evolving model of compounding contributions of 1p gene aberrations toward tumor suppressor inactivation in neuroblastoma.

Evolution of Therapy for Older Patients With Acute Myeloid Leukemia: How Should We Use Currently Available Agents?

Most patients with newly diagnosed acute myeloid leukemia (AML) are 65 years or older. The treatment of AML in older patients has been characterized by distinct patient- and disease-related challenges that have impeded the meaningful progress that has been observed in younger patients with AML. Higher rates of comorbidities and frailty contribute to higher rates of treatment-related complications, whereas adverse disease features such as poor-risk genomics and secondary AML are associated with therapeutic resistance and shortened survival. Intensive chemotherapy and allogeneic stem cell transplant, although still considered standard for many newly diagnosed patients with AML, may not be appropriate for a larger subset of older patients with AML. Lower-intensity approaches such as hypomethylating agents have been widely applied for newly diagnosed older and unfit patients with AML, improving tolerability among this subset, but providing more modest response rates. Numerous analyses have attempted to tackle the utility of higher- versus lower-intensity therapy in older AML and identify the factors that can help choose the approach that best optimizes tolerability and efficacy. Recently, a greater understanding of the genomic and biologic heterogeneity of AML has led to better risk stratification and has contributed to the development of specific targeted therapies that are starting to narrow the gap between safety and efficacy. Newly approved agents, such FLT3 (FMS-like tyrosine kinase 3) inhibitors, IDH1 and IDH2 inhibitors, and the BCL2 inhibitor venetoclax, as well postremission maintenance therapy with CC-486 (oral 5-azacitidine), are being systematically incorporated into the evolving treatment of older patients with newly diagnosed AML.

Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib.

BACKGROUNDImpressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals’ disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden.AIMTo assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients.METHODSThis retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib.RESULTSThe median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone.CONCLUSIONTARE with/without sorafenib according to individuals’ disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.

Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021.

Simple SummaryThe better understanding of disease biology, the availability of new effective drugs and the increased awareness of patients’ heterogeneity in terms of fitness and personal expectations has made the current treatment paradigm of AML in the elderly very challenging. Here, we discuss the evolving criteria used to define eligibility for induction chemotherapy and transplantation, the introduction of new agents in the treatment of patients with very different clinical conditions, the implications of precision medicine and the importance of quality of life and supportive care, proposing a simplified algorithm that we follow in 2021.Acute myeloid leukemia (AML) in older patients is characterized by unfavorable prognosis due to adverse disease features and a high rate of treatment-related complications. Classical therapeutic options range from intensive chemotherapy in fit patients, potentially followed by allogeneic hematopoietic cell transplantation (allo-HCT), to hypomethylating agents or palliative care alone for unfit/frail ones. In the era of precision medicine, the treatment paradigm of AML is rapidly changing. On the one hand, a plethora of new targeted drugs with good tolerability profiles are becoming available, offering the possibility to achieve a prolonged remission to many patients not otherwise eligible for more intensive therapies. On the other hand, better tools to assess patients’ fitness and improvements in the selection and management of those undergoing allo-HCT will hopefully reduce treatment-related mortality and complications. Importantly, a detailed genetic characterization of AML has become of paramount importance to choose the best therapeutic option in both intensively treated and unfit patients. Finally, improving supportive care and quality of life is of major importance in this age group, especially for the minority of patients that are still candidates for palliative care because of very poor clinical conditions or unwillingness to receive active treatments. In the present review, we discuss the evolving approaches in the treatment of older AML patients, which is becoming increasingly challenging following the advent of new effective drugs for a very heterogeneous and complex population.

PD19-12 EXAMINING THE PREDICTIVE ROLE OF LYMPH-VASCULAR INVASION IN PATIENTS WITH VERY HIGH-RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II (PD19)1 Sep 2021PD19-12 EXAMINING THE PREDICTIVE ROLE OF LYMPH-VASCULAR INVASION IN PATIENTS WITH VERY HIGH-RISK PROSTATE CANCER Nikola Rakic, Ivan Rakic, Jacob Keeley, Christian Meyer, Markus Graefen, Randi Pose, Perre Tennstedt, Nicholas Corsi, Chandler Bronkema, Akshay Sood, Sohrab Arora, Craig Rogers, Mani Menon, and Firas Abdollah Nikola RakicNikola Rakic More articles by this author , Ivan RakicIvan Rakic More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Christian MeyerChristian Meyer More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Randi PoseRandi Pose More articles by this author , Perre TennstedtPerre Tennstedt More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Chandler BronkemaChandler Bronkema More articles by this author , Akshay SoodAkshay Sood More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Craig RogersCraig Rogers More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002008.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymph-vascular invasion (LVI) at radical prostatectomy (RP) is recognized as an adverse pathological feature in patients with prostate cancer (PCa). Recent literature showed a detrimental impact of LVI on overall survival in all patients with PCa, regardless of risk stratification. That said, the predictive performance of LVI in patients with very have high-risk disease, where it could serve as a guide for the necessity of multimodal treatment has not been elucidated. We tested the hypothesis that LVI is an independent predictor of cancer-specific mortality (CSM) in patients with very high-risk PCa. METHODS: We included 2,058 PCa cM0 patients who underwent RP with lymph node dissection, between 2001 and 2019, in two tertiary care centers. Included patients were considered high-risk due to harboring ≥2 of the following adverse disease features: ≥pT3b stage, pathological Gleason 8-10, and/or positive nodal involvement (pN1). Cumulative incidence curves were used to estimate CSM, after accounting for other cause mortality. Regression analysis tested the relationship between LVI and CSM after accounting for the following covariates: PSA, pathological tumor stage, Gleason grade, pathological nodal status, and surgical margin status. RESULTS: Within our cohort, most patients had a pT3b disease (86.2%), pN1 status (75.4%), positive margins (PSM) (73.9%), LVI (59.0%) and pathological Gleason 9 disease (69.1%). Median (IQR) follow-up of the cohort was 36 months (13-61). At 5-year, CSM rate was 11.2% in patients with LVI vs 7.2% in patients without LVI (p=.03). However, on multivariable analysis, LVI was not an independent predictor of less favorable CSM rate (hazard ratio [HR]:1.071, 95% CI:0.718–1.599, p=0.7366). Covariates that were found to be independent predictors of CSM included Gleason score ≥ 8 (HR: 5.668, 95% CI: 2.704-11.830, p<.0001), PSM (HR: 1.774, 95% CI: 1.080-2.915, p=.02), pN1 (HR: 2.147, 95% CI: 1.278-3.607, p=.003), and stage ≥ pT3b (HR: 3.113, 95% CI: 1.334-7.265, p=.008). CONCLUSIONS: In patients with very high-risk PCa, where the stakes are the highest, and multimodal treatment is frequently discussed after radical prostatectomy, LVI fails to provide further guidance when compared to routinely available and utilized clinical and pathological features. In a quest to continuously optimize outcomes for our patients, our findings highlight an important shortcoming for LVI in very high-risk patients and further show the prognostic value of widely accepted adverse disease characteristics. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e366-e366 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nikola Rakic More articles by this author Ivan Rakic More articles by this author Jacob Keeley More articles by this author Christian Meyer More articles by this author Markus Graefen More articles by this author Randi Pose More articles by this author Perre Tennstedt More articles by this author Nicholas Corsi More articles by this author Chandler Bronkema More articles by this author Akshay Sood More articles by this author Sohrab Arora More articles by this author Craig Rogers More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

P175 Comorbidities in psoriatic arthritis: a systematic review and meta-analysis

Abstract Background/Aims Psoriatic arthritis (PsA) is a heterogeneous disease with numerous articular phenotypes and extra-articular disease features. Patients with PsA have a higher risk of developing comorbidities. Studies in other chronic rheumatic diseases have shown comorbidity burden to be associated with poorer outcomes. The aims of this systematic review and meta-analysis were to: 1) describe the prevalence of comorbidities in PsA, 2) compare the incidence and/or prevalence of comorbidities between PsA and control populations; and 3) examine the impact of comorbidities on PsA outcomes. Methods Medline, PubMed, Scopus, and Web of Science were systematically searched using a predefined protocol in accordance with PRISMA guidelines. Exclusion criteria included: studies with risk of being non-representative of general PsA populations, studies reporting only one comorbidity, studies reporting psoriatic disease manifestations and pathomechanistically related conditions and other inflammatory arthritides. Where possible, meta-analysis was performed using random-effects models. Results A total of 3817 publications were returned by the literature search. After exclusions and de-duplication, 39 studies remained. Sample sizes ranged from 32 to 35,061 with a total of 158,797 PsA patients. The most frequently studied comorbidities were diabetes (n = 32 studies), hypertension (31) and hyperlipidaemia (18). A meta-analysis for the prevalence of 21 commonly reported comorbidities was performed (table 1). The most prevalent comorbidities were hypertension (pooled prevalence 34%), metabolic syndrome (29%), obesity (27%), hyperlipidaemia (24%) and any cardiovascular disease (19%). Eleven studies compared comorbidities between PsA and control groups. All except three studies matched or adjusted for potential confounders such as age and sex. Virtually all individual comorbidities had higher incidence and prevalence in the PsA group. The comorbidities and effect estimates were too heterogeneous to permit meta-analysis. Five studies reported the impact of comorbidities on PsA outcomes. In most studies, PsA patients with comorbidity had greater pain, functional limitation, and poorer quality of life than those without. One study reported that metabolic syndrome-related comorbidities were significantly associated with TNFi discontinuation. P175 Table 1:Meta-analysis estimates for prevalence of individual comorbidities.No. of studiesNo. of individualsPooled prevalence95% confidence intervalI2, %RangeAny CVD124436919.47.8-34.11003.1-70.5Any IHD8296719.27.1-11.6970.6-18.2Angina358283.61.4-6.6941.9-5.1Myocardial infarction10176283.22.3-4.2871.3-8.1Heart failure8234551.31.0-1.7720.6-3.1Stroke15428722.81.5-4.5980.0-21.8PVD8446291.60.5-3.3990.0-6.2Hypertension318501434.228.6-40.21006.4-62.7Diabetes mellitus328997212.910.7-15.2992.0-34.1Hyperlipidaemia185981624.217.4-31.81002.9-79.8Obesity152789027.424.5-30.49512.7-39.8Metabolic syndrome5110928.814.0-46.2969.9-44.0Any GI disease5119769.97.9-12.0716.0-16.0Liver disease10732893.40.1-9.61000.0-26.5Any pulmonary disease66837012.36.3-19.81005.0-22.7COPD6125173.40-10.4991.1-17.3Depression149154111.97.4-17.21000.8-27.2Any cancer11636705.24.2-6.4961.5-9.2Renal disease8330512.50.8-4.9991.0-8.1Osteoporosis4182159.33.0-18.3993.8-14.0Thyroid disorders52531610.57.7-13.7940.6-15.0Stroke includes cerebrovascular accidents and transient ischaemic attacks. PVD, peripheral vascular disease; COPD, chronic obstructive pulmonary disease; GI gastrointestinal. Conclusion Comorbidities, particularly cardiometabolic disorders, were highly prevalent in PsA and more common than in controls. Comorbidities were associated with adverse disease features, but more research is needed on their impact on longitudinal clinical outcomes. Disclosure Z.J. Syrimi: None. S. Gupta: None. S.S. Zhao: None. D.M. Hughes: None.

Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed...

Has the COVID-19 outbreak changed the way we are treating prostate cancer? An EAU - YAU Prostate Cancer Working Group multi-institutional study.

IntroductionThe COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology.Material and methodsConsecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year.ResultsA total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19.ConclusionsOur results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control.

Age is an independent predictor of outcome in endometrial cancer patients: An Israeli Gynecology Oncology Group cohort study.

Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P=.025), deep myoinvasion (44% vs 29%, P=.001) and lymphovascular involvement (22% vs 15%, P=.024). Surgical staging was performed less frequently among older women (33% vs 56%; P<.001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P<.001). On multivariable analysis, age remained a significant predictor for recurrence (HR=1.75, P=.007), death of disease (HR=1.89, P=.003) and death (HR=2.4, P<.001). Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population.

MM-167: Phenotypic and Prognostic Evaluation of Circulating Plasma Cells in Newly Diagnosed Multiple Myeloma Detected with Next-Generation Flow Cytometry (NGF)

Context: The apparent heterogeneity of multiple myeloma (MM) necessitates the identification of novel biomarkers with a strong prognostic value. The presence of circulating plasma cells (CPCs) in newly diagnosed patients (NDMM) has been proposed as a valuable prognostic biomarker, though current methodologies reported yielded heterogeneous results due to variations in their detection efficacy. Objective: To evaluate the characteristics and prognostic value of CPCs, utilizing highly sensitive next-generation flow (NGF) cytometry, able to detect aberrant plasma cells (APCs) at levels reaching 10−6. Design, Patients, and Methods: Peripheral blood (PB) and matched bone marrow (BM) samples from 325 NDMM patients were prospectively evaluated for the presence of APCs according to Euroflow-NGF protocol for a median LOD reached of 3.6 × 10−6. CPC numbers correlated with various clinical parameters and the median follow-up period since CPC assessment was 24 months. Main outcome measures: Clinical outcome endpoints considered were the type of response to induction therapy and PFS. Our hypothesis was that higher CPC numbers would correlate with adverse prognostic features and worse clinical outcomes. Results: CPCs were detected in 288/325 (88.6%) samples (range, 0.0002% - 63.8% of PBNCs). CPCs and matched BM APCs had similar phenotypic characteristics; notably, when two or more phenotypically distinct APC-subsets were detectable in BM, the same subsets were also present in PB with similar relative frequency. Higher CPC numbers (>0.1% of PBNCs) correlated with increased BM infiltration, ISS-3 stage, and high-risk cytogenetics (p Conclusions: NGF enables the detection of rare CPCs in NDMM, many of which would have been falsely missed with a lower sensitivity approach. The similarity of CPCs with BM APCs and the strong correlation of higher CPC numbers with adverse disease characteristics highlight a valuable surrogate prognostic tool, which could representatively replace standard BM invasive methods.

Durable Responses Observed in Elderly AML Patients Unfit for Intensive Chemotherapy with First-in Class Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with LDAC: Phase II Open-Label Study

Durable Responses Observed in Elderly AML Patients Unfit for Intensive Chemotherapy with First-in Class Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with LDAC: Phase II Open-Label Study

Next Generation Flow Cytometry Provides a Standardized, Highly Sensitive and Informative Method for the Analysis of Circulating Plasma Cells in Newly Diagnosed Multiple Myeloma: A Single Center Study in 182 Patients

Introduction: The apparent heterogeneity of multiple myeloma (MM) constitutes a key challenge in the clinical management and the design of effective therapeutic interventions, while it entails the identification of biomarkers with a strong prognostic value. In this context and taking into account patients' inconvenience to invasive bone marrow (BM) aspiration, the assessment of circulating plasma cells (CPCs) in liquid biopsies, at the time of diagnosis, has been proposed as a useful assay with prognostic value. Different methodologies have been applied for the detection of CPCs; the most common is the use of multicolor flow cytometry (MFC), mainly of 2-, 4-, or 6-color combination panels, which however yielded heterogeneous results due to variations in the detection efficacy of each approach. In the present study, we applied the standardized and highly sensitive Next Generation Flow Cytometry (NGF) approach, to detect CPCs in diagnostic MM peripheral blood (PB) samples, we compared their phenotypic characteristics with the aberrant clonal cells of BM matched samples and we correlated their presence with disease characteristics. Patients and Methods: PB and BM matched samples from 182 consecutive MM patients, at diagnosis, were evaluated for the presence of aberrant plasma cells (APCs) following the standard operating procedures (SOP) of NGF, according to EuroFlow guidelines. All these patients were diagnosed and treated in a single center (Department of Clinical Therapeutics, N.K. University of Athens, Greece). Samples were collected in EDTA-anticoagulated tubes and treated with the bulk-lysis procedure. Recovered cells were stained with antibodies against surface CD19-PEC7, CD27-BV510, CD38-FITC, CD45-PERCP, CD56-PE and CD138-BV421 and the intracellular CyIgκ-APC and CyIgλ-APCC750 to verify clonality. Six to ten million cells were acquired per sample, thus reaching a median Limit of Detection (LOD) of 3.5x10-6. Optimal PMT voltages were set according to the EuroFlow SOP for instrument set-up and daily performance status of FACSCANTOII was monitored with both CS&amp;T (BD) and Rainbow beads (Spherotech Inc, Lake Forest, IL). Results: CPCs were detected in 158/182 (86.8%) MM diagnostic samples within a range of 0.0002% to 63.8% of total PB nucleated cells (PBNCs). The CPCs showed the same aberrant phenotype as the one detected in the BM for all cases, although with a significantly reduced intensity for the markers CD27, CD38, CD138 and CD56. When more than one phenotypically distinct subgroups were detectable in the BM, the same phenotypic subsets were present in the PB with the same relative frequency for &gt;90% of bi/multi-phenotypic cases. The higher number of CPCs (&gt;0.1% of all PBNCs) strongly correlated with an increased BM infiltration rate by myeloma cells (p&lt;0.0001), with ISS-3 disease stage (p&lt;0.0001) and with the presence of high-risk cytogenetics [t(4;14), t(14;16) and/or del(17p53); p&lt;0.0001]. There was also weaker correlation between high number of CPCs and high serum creatinine levels (p=0.015). Inversely, the absence of CPCs or the presence of CPCs at numbers ≤0.001% correlated with lower serum β2-microglobulin (p&lt;0.0001), with higher hemoglobin levels (p&lt;0.0001) and with the presence of an elevated normal plasma cell compartment within the BM (i.e. ≥5% of all PCs; r2=0.84, p&lt;0.0001). There was no association between the CPC number and the therapeutic response to induction treatment (IMWG criteria). Despite the short follow-up period (median of 16 months), there is a trend for inferior PFS in patients with high CPCs (p=0.16). Conclusions: The NGF approach using the EuroFlow protocol enables the detection of even rare CPCs in diagnostic MM PB samples, due to the high number of cells acquired and the elegantly elaborated 8-color marker combinations which allows for the detection of CPCs with even a non-typical phenotype. Our matched PB and BM analysis revealed that BM APCs and CPCs share very similar characteristics suggesting that liquid biopsy offers a representative alternative for the phenotypic characterization of BM APCs. The correlation of high CPCs with adverse disease characteristics suggests that the quantification of CPCs by standardized NGF may emerge as a valuable surrogate prognostic biomarker which could replace other invasive methods or other less informative assays. Disclosures Terpos: Janssen: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Celgene: Honoraria. Gavriatopoulou:Amgen: Honoraria; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses. Kastritis:Genesis: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria. Dimopoulos:Sanofi Oncology: Research Funding.