CD56 Expression Is an Important Prognostic Factor in Multiple Myeloma Even with Bortezomib Induction

Objectives: In this retrospective study, we evaluated the impact of CD56, CD117, and CD28 expression on clinical characteristics and survival in newly diagnosed myeloma patients treated with bortezomib-based induction therapy. Methods: We analyzed 110 myeloma patients. Immunophenotype was determined using panels consisting of CD19/CD38/CD45/CD56/CD138 and CD20, CD28, and CD117 were used additionally. All samples were tested for recurrent chromosomal aberrations. Results: CD56, CD117, and CD28 expression rates were 71, 6, and 68%, respectively. The lack of CD56 expression was associated with light chain myeloma. The lack of CD117 expression was associated with elevated creatinine levels (p = 0.037). We discovered the correlation between CD 28 expression and female gender. The median progression-free survival (PFS) for patients with revised International Staging System stage 2 disease with CD56 expression or the lack of CD56 expression was 20.5 vs. 13.8 months (p = 0.03). In patients undergoing autologous hematopoietic stem cell transplantation (aHSCT), we found no difference in PFS and overall survival regarding the CD56 expression. We found no impact of CD117 and CD28 expression on PFS in patients regarding aHSCT. Conclusions: Induction treatment incorporating bortezomib diminishes the negative impact of the lack of CD117 expression and aberrancy of CD28 but does not overcome the negative impact of the lack of CD56 expression.

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Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) in CLL: First Results of An EBMT Randomized Trial Comparing Autotransplant Versus Wait and Watch.

Blood ◽

10.1182/blood.v114.22.877.877 ◽

2009 ◽

Vol 114 (22) ◽

pp. 877-877

Author(s):

Mauricette Michallet ◽

Peter Dreger ◽

Laurent Sutton ◽

Ronald Brand ◽

Sue Richards ◽

...

Keyword(s):

Conflicts Of Interest ◽

Progression Free Survival ◽

Disease Status ◽

Primary Objective ◽

Phase Iii ◽

Induction Treatment ◽

Hematopoietic Stem ◽

Binet Stage ◽

The Impact

Abstract Abstract 877 This phase-III randomized EBMT-intergroup trial studied the impact of a consolidating autoHSCT vs no consolidation for patients with CLL in Binet stage A progressive, B or C , in CR, nodular PR or VGPR after first or second line therapy. The primary objective was to show that autoHSCT increased the 5-year progression-free survival (PFS) by 30%. Although it had been calculated that 270 patients were to be randomized, the study was terminated by the steering committee in July 2007 due to poor accrual. Here we present a first analysis based on 69% of expected follow-up forms. Results: Between November 2001 and July 2007, 223 patients were enrolled (SFGM-TC/FCLLG n=98, MRC n=62, GCLLSG n=32, SAKK n=10, other EBMT centers n=17). There were 74% males and 26% females. Binet stages were progressive A 13%, B 67%, C 20%; 59% were in CR, and 41% in very good or nodular PR. Of note, SFGM-TC/FCLLG included only patients in CR. 82% of the patients were enrolled in 1st, and 18% in 2nd remission. Patients were randomized between group 1 (autoHSCT n=112) and group 2 (observation n=111) after an induction treatment which was left at the discretion of the investigators. Median PFS was 43 months in the observation group but not reached in the autoHSCT group; 5-year PFS was 48% and 65%, respectively (p=0.005). Accordingly, autoHSCT halved the relapse risk (5-year relapse incidence 25% vs. 51%; HR 0.4 [0.23-0.71], p=0.002). Cox modeling for randomization arm, Binet stage, disease status, line of treatment, contributing group (country), and the interaction between randomization arm and contributing group confirmed that autoHSCT significantly improved PFS (HR 0.41 [0.23-0.75] p=0.004). The beneficial effect of autoHSCT was stable over all contributing groups although patients accrued by SFGM-TC/FCLLG overall had a significantly better PFS than patients from other countries (HR 0.2 [0.08-0.55], p=0.001). At 5 years, the probability of OS was 92% and 91% for autoHSCT and observation, respectively. Significant differences in terms of non-relapse death were not observed. At the last follow up, among 205 evaluable patients, 186 are alive (147CR, 39 relapse), 19 died (14 from relapse and 5 from non-relapse causes) . In conclusion, in patients with CLL in first or second remission, consolidating autoHSCT reduces the risk of progression (PFS) by more than 50%, but has no effect on overall survival. Disclosures: No relevant conflicts of interest to declare.

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Understanding the Impact of Bullying in a Unionized U.S. Public Sector Workforce

Workplace Health & Safety ◽

10.1177/2165079919883286 ◽

2019 ◽

Vol 68 (3) ◽

pp. 139-153 ◽

Cited By ~ 1

Author(s):

Mazen El Ghaziri ◽

Shellie Simons ◽

Jane Lipscomb ◽

Carla L. Storr ◽

Kathleen McPhaul ◽

...

Keyword(s):

Public Sector ◽

Organizational Climate ◽

Negative Impact ◽

Multinomial Logistic Regression ◽

Female Gender ◽

Bargaining Unit ◽

Organizational Level ◽

Organizational Impact ◽

Cross Sectional ◽

The Impact

Background: Workplace Bullying (WPB) can have a tremendous, negative impact on the victims and the organization as a whole. The purpose of this study was to examine individual and organizational impact associated with exposure to bullying in a large U.S. unionized public sector workforce. Methods: A cross-sectional Web-based survey was conducted among 16,492 U.S. state government workers. Survey domains included demographics, negative acts (NAs) and bullying, supportiveness of the organizational climate, and individual and organizational impacts of bullying. Multinomial logistic regression was used to assess the impact among respondents who reported exposure to bullying. Findings: A total of 72% participants responded to the survey (n = 11,874), with 43.7% (n = 5,181) reporting exposure to NAs and bullying. A total of 40% (n = 4,711) participants who experienced WPB reported individual impact(s) while 42% ( n = 4,969) reported organization impact(s). Regular NA was associated with high individual impact (negatively impacted them personally; odds ratio [OR] = 5.03) when controlling for other covariates including: female gender (OR =1.89) and job tenure of 6 to 10 years (OR = 1.95); working in a supportive organizational climate and membership in a supportive bargaining unit were protective of high impact (OR = 0.04 and OR = 0.59, respectively). High organizational impact (transferring to another position) was associated with regular NA and bullying (OR = 16.26), female gender (OR = 1.55), providing health care and field service (OR = 1.68), and protective effect of organizational climate (OR = 0.39). We found a dose-response relationship between bullying and both individual and organizational-level impact. Conclusion/Application to Practice: Understanding the impacts of WPB should serve to motivate more workplaces and unions to implement effective interventions to ameliorate the problem by enhancing the organizational climate, as well as management and employee training on the nature of WPB and guidance on reporting.

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Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study

Scientific Reports ◽

10.1038/s41598-019-54897-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Graziamaria Corbi ◽

Francesco Cacciatore ◽

Klara Komici ◽

Giuseppe Rengo ◽

Dino Franco Vitale ◽

...

Keyword(s):

Longitudinal Study ◽

Cox Model ◽

Survival Rates ◽

Staging System ◽

Female Gender ◽

Term Survival ◽

Fractional Polynomial ◽

The Impact

AbstractAim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.

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Outcome of Patients with Relapsed/Refractory AIDS-Related Lymphoma In the AIDS Malignancy Consortium (AMC) 1997–2008

Blood ◽

10.1182/blood.v116.21.3569.3569 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3569-3569

Author(s):

Ariela Noy ◽

Ulas Darda Bayraktar ◽

Neel Gupta ◽

Adam M. Petrich ◽

Page Moore ◽

...

Keyword(s):

Conflicts Of Interest ◽

Progression Free Survival ◽

Standard Of Care ◽

Infectious Complications ◽

High Dose ◽

Hiv Diagnosis ◽

Curative Intent ◽

Hematopoietic Stem ◽

The Impact ◽

Aids Related Lymphoma

Abstract Abstract 3569 Introduction: High dose therapy (tx) with autologous hematopoietic stem cell transplantation (AHSCT) in (rel/rfr) lymphoma is the standard of care in the general population with chemosensitive disease. The feasibility of second line therapies (Tx) and AHSCT in (rel/rfr) AIDS related lymphoma (ARL) has been shown in a number of trials. However, the true impact of 2nd line tx and AHSCT is unknown, as nearly all studies focus on those already with disease sensitive to 2nd therapy going onto transplantation. The only recent study capturing patients (n=50) before 2nd line tx showed 49% progression-free survival (Re et al. Blood 2009). Here, we retrospectively analyzed the outcome of patients (pts) presenting at 13 US AIDS Malignancy Consortium sites with (rel/rfr) ARL in the HAART era. Patients and Methods: HIV-positive pts initiating tx for (rel/rfr) ARL between 1997–2008 were included. Overall survival (OS) was calculated from the initiation of 2nd line tx. Results: A total of 126 pts received 2nd line tx. Only those 88 pts who received 2nd line with curative intent to treat (ITT) were included in the analysis. Baseline and selected clinical characteristics are summarized in the table. Median CD4 at HIV diagnosis was 110 (n=37) with a range of 12 to 1000. At ARL dx, median CD4 was 152 (5-803). 47% had an opportunistic infection (OI) prior to ARL. 2nd line tx were: ICE (n=34), EPOCH (n=16), ESHAP (n=11), High-dose MTX variants (n=10), Hodgkin's specific tx (n=5), DHAP (n=4) and others (n=8). Thirty-two (36%) had a response to 2nd line tx (CR, n=21; PR, n=11). Of 50 pts with grade ≥3 toxicities, the most common were thrombocytopenia (46%) and neutropenic fever (44%). Six pts died during 2nd line tx due to infectious complications, with 1 aspergillosis. Best response to 2nd line tx: Thus, CR/PR was 32/88 (36%) in ITT analysis. Only 10/32 CR/PR pts went onto AHSCT due to availability and changing treatment paradigms. Conditioning was BEAM (n=9) and Bu/Cy (n=7). No pt went onto allotransplant. At AHSCT day +90, 10 pts were in CR. For all pts, median follow-up was 122 weeks (range, 8–597), median OS was 38 weeks (95% CI, 27–63). Reflecting the 65% prevalence of pts refractory to 2nd line tx in the non-AHSCT group, OS was longer in pts who underwent AHSCT compared to those who did not (2-year OS: 55.3% vs. 31.0%). Surprisingly, 1-year OS in the CR/PR pts was 87.5±12.5% for AHSCT and 81.8±8.2% for non-AHSCT. One Burkitt pt survived a year without AHSCT. Discussion: Rel/rfr ARL was treated aggressively in this largest ever reported cohort, but CR/PR was only 32/88 (36%) in ITT analysis. Not all CR/PR pts went onto AHSCT due to changing treatment paradigms and regional availability. Aggressive 2nd line tx and ASHCT was feasible despite prior low CD4 and OI, but DFS may be possible without transplant. We cannot draw conclusions about the impact of AHSCT from this retrospective cohort. Similarly, it is not known whether survival in (rel/rfr) ARLs is equivalent to the HIV negative population. The current paradigm is to offer pts with rel/rfr ARLs AHSCT if disease is chemosensitive and no contraindication exist. New strategies are needed for 2nd line therapy, particularly in rel/rfr BL. Disclosures: No relevant conflicts of interest to declare.

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Kinetics of Engraftment and Predictors of Outcome in Patients with Advanced Chronic Lymphocytic Leukaemia (CLL) After Treatment with Low Dose Total Body Irradiation (TBI) Followed by related or unrelated hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v118.21.4532.4532 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4532-4532

Author(s):

Karin Hebenstreit ◽

Simona Iacobelli ◽

Ann-Kathrin Eisfeld ◽

Christian Pfrepper ◽

Thoralf Lange ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Transplantation ◽

Progression Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Cell Donor ◽

Donor Chimerism ◽

The Impact ◽

Kinetics Of

Abstract Abstract 4532 Introduction: In an unicenter analysis we investigated the impact of allogeneic hematopoietic cell transplantation (RIC-HCT) after reduced intensity conditioning on the kinetics of engraftment and predictor of outcome in 50 patients with advanced CLL. Patient and Methods: Patients in advanced stage CLL (n=50) received Fludarabine 30mg/m2 on day -4 to -2 and 2Gy TBI on day 0 followed by cyclosporine and MMF from unrelated (n=40) or related (n=10) donors between June 1999 and March 2010 at the University of Leipzig. The majority of patients (n= 35) were male, had Binet C (n=37, 74%) at RIC-HCT. The median age was 58 (range 44–69) years. Of 48 patients for whom cytogenetic analyses were available, 22 (46%) had unfavourable cytogenetics including del 17 or del 11q. Three (6%) patients had CR, 27 (54%) PR, 7 (14%) progressive disease, 12 (24%) stable disease and one (5%) relapse at RIC-HCT. Resistance to first line therapy was present in 25 (50%) patients, whereas 12 (24%) were resistant to Fludarabine. Richter’s transformation was found in six patients (12%). Chimerism was detected in bone marrow and peripheral blood on T-lymphocytes and B-lymphocyte subpopulation after sorting at monthly intervals in the posttransplant period and than in 6 months interval. Results: Hematological toxicities after RIC-HCT were moderate. The majority of patients (96%) engrafted with neutrophiles >500/μ L median at day 22 after HCT. Six (12%) and 15 (30%) patients maintained absolute neutrophil counts (ANC) >0,5 × 109/L and platelet counts >50 × 109/L, respectively. T-cell donor chimerism increased to >95% at day 56 and B-cell donor chimerism to 94% at day +360, respectively. B-CLL cells disappeared completely on day +360 (median 0%). Overall survival (OS) at 4 years was 51%, Non relapse related mortality (NRM) 30%, Progression-free survival 33% and progression/relapse 37%. The most common causes of NRM were GvHD (n= 7; 14%) and sepsis (n=3, 6%). Factors significantly associated with increased risk of relapse/progression were intermediate/advanced disease vs. CR/PR1 (p=0.022) and lymphocytes ≥ 5 × 109/L vs. < 5 × 109/L (18% vs. 58%, p= 0.00) at 12 months in univariate analysis. Conclusion: Full donor T-cell chimerism was reached early after HCT, while B-cell reconstitution was observed only 1.5 years after RIC-HCT despite the absence of evident disease by 360 days after RIC-HCT. Best predictor for Progression-free survival (PFS) was CR or PR1. Disclosures: Pönisch: Mundipharma: Honoraria, Research Funding.

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Factors Related to Oral Health-Related Quality of Life of Independent Brazilian Elderly

International Journal of Dentistry ◽

10.1155/2013/705047 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 24

Author(s):

Karla Giovana Bavaresco Ulinski ◽

Mariele Andrade do Nascimento ◽

Arinilson Moreira Chaves Lima ◽

Ana Raquel Benetti ◽

Regina Célia Poli-Frederico ◽

...

Keyword(s):

Quality Of Life ◽

Oral Health ◽

Negative Impact ◽

Female Gender ◽

Lower Class ◽

Structured Interviews ◽

Cross Sectional ◽

Posterior Teeth ◽

The Impact

The aim of this cross-sectional study was to assess the factors associated with the impact of oral health on the quality of life in a sample of 504 Brazilian independent elderly. Data collection included oral examinations and structured interviews. The simplified form of the Oral Health Impact Profile (OHIP-14) was used to measure OHRQoL. Information on sociodemographic characteristics, use of dental services, and subjective measures of health was collected. Poisson regression within a hierarchical model was used to data analyses. The following variables were associated with a negative impact on OHRQoL: female gender (PR = 1.40; CI 95%: 1.11–1.77); lower class (PR = 1.58; CI 95%: 1.13–2.20); up to 3 occluding pairs of posterior teeth (PR = 1.88; CI 95%: 1.13–3.14); at least one untreated caries (PR = 1.28; CI 95%: 1.06–1.54); curative reasons for the last dental appointment (PR = 1.52; CI 95%: 1.15–2.00); poor self-perception of oral health (PR = 2.49; CI 95%: 1.92–3.24); and poor perception of dental care provided (PR = 1.34; CI 95%: 1.12–1.59). The younger elderly also noticed this negative impact. These findings showed that the clinical, sociodemographic, and subjective factors evaluated exerted a negative impact on OHRQoL in elderly people. Health authorities must address all these factors when planning interventions on oral health for this population.

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ABCB1 Expression in Acute Myeloid Leukemia (AML): A Possible Predictive Value for Treatment Resistance?

Blood ◽

10.1182/blood.v124.21.3618.3618 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3618-3618

Author(s):

Stephany Corrêa ◽

Eliana Abdelhay ◽

Peter Paschka ◽

Verena I. Gaidzik ◽

Rocio Hassan ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Induction Treatment ◽

Mrna Levels ◽

Complex Karyotype ◽

Hematopoietic Stem ◽

Expression Levels ◽

The Impact ◽

Acute Myeloid

Abstract Introduction: Over the last years, there has been a tremendous increase in understanding acute myeloid leukemia (AML) biology and a great effort has been taken in order to improve AML chemotherapy strategies. However, the growing knowledge of leukemia associated molecular mechanisms just started to translate into improved outcome. With regard to conventional chemotherapy multidrug resistance (MDR) is a persisting problem and the impact of ABCB1 (MDR1) expression is still controversially discussed. Methods: In this study we evaluated the ABCB1 expression using qRT-PCR and gene expression profiling (Affymetrix U133plus2.0 arrays) in 250 diagnostic AML samples derived from patients enrolled on a prospective treatment trial of the German-Austrian AML Study Group (AMLSG 07-04 trial; NCT00151242), in which patients were treated with an intensive anthracycline/cytarabine-based induction therapy. Findings were also evaluated in 154 TCGA AML cases receiving a 7+3 induction treatment (data available at http://cancergenome.nih.gov/) and put into perspective with previous reports. Furthermore, we investigated ABCB1 expression associated gene signatures and examined epigenetic regulation mechanisms by COBRA and methyl-CpG immunoprecipitation sequencing (MCIp-seq) in selected cases. Results: Our global analysis showed that patients who obtained a complete response (CR) following double induction therapy had lower ABCB1 mRNA levels compared to patients with refractory disease (RD) (p=0.07). Regarding cytogenetic AML subtypes, ABCB1 mRNA levels varied among the different cytogenetic groups with the complex karyotype group showing the highest ABCB1 and the inv(16) group the lowest ABCB1 expression levels. A comparison of CR versus RD cases within the cytogenetically determined prognostic groups showed that in the intermediate [CN-AML, t(11q23), and other intermediate risk cytogenetic aberrations (othersinter)] and poor risk groups (complex karyotype and othershigh), RD patients presented with significantly higher ABCB1 mRNA levels (p=0.02). Similarly, patients with favorable risk cytogenetics [t(8;21) and inv(16)], who achieved a CR, presented with lower ABCB1 levels compared to the ones, who were refractory. Patients with the lowest ABCB1 expression quartile (ABCB1low) showed significantly longer event-free survival (EFS) times than patients in the highest quartile cohort (ABCB1high) (median EFS 322 vs 105 days; p=0.02), while no differences were observed with regard to overall survival. In accordance, there was a significant enrichment of RD cases in the ABCB1high patient group (p=0.03). Next, in order to better understand the regulation of ABCB1 in AML, we specifically evaluated the DNA methylation level of a previously identified GC box important for ABCB1 expression regulation in CML and we performed global analyses of the entire ABCB1 5' region. While both analyses did not reveal significant differences, further investigation of an ABCB1 associated gene pattern showed a correlation with CD34 and KIT expression (p<0.001). This suggests that like in CML, ABCB1 might be regulated by WNT, and in line, normal CD34+ hematopoietic stem cells also showed high ABCB1 expression levels. Conclusions: In summary, our data provide further evidence for a potential impact of ABCB1 deregulation on the response to AML chemotherapy, especially in more stem cell like leukemia cohorts as well as cytogenetically high risk AML. While we are currently further investigating the involvement of the Wnt/β-catenin pathway in the regulation of ABCB1 transcription in AML, further integration of molecular findings are warranted to better decipher the underlying drug resistance mechanisms. Ultimately, these analyses will improve patient management by adding valuable predictive biomarkers. Disclosures No relevant conflicts of interest to declare.

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Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma

Frontiers in Oncology ◽

10.3389/fonc.2021.668099 ◽

2021 ◽

Vol 11 ◽

Author(s):

JingSong He ◽

XiaoYan Yue ◽

DongHua He ◽

Yi Zhao ◽

Yang Yang ◽

...

Keyword(s):

Multiple Myeloma ◽

Prognostic Factors ◽

Early Stage ◽

Progression Free Survival ◽

Staging System ◽

Serum Lactate ◽

Single Site ◽

Serum Lactate Dehydrogenase ◽

Newly Diagnosed ◽

International Staging System

BackgroundExtramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.MethodsIn this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.ResultsThe overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (>1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, >245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.ConclusionsThis study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.

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Randomized phase II study on the influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab (Bev) or cetuximab (Cet), as first line therapy of patients (pts) with RAS wild-type metastatic colorectal carcinoma (mCRC) and <3 baseline circulating tumor cells (bCTCs).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3549 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3549-3549

Author(s):

Enrique Aranda ◽

Pilar Garcia-Alfonso ◽

Jose María Vieitez ◽

Maria Jose Ortiz ◽

Carlos López-López ◽

...

Keyword(s):

Phase Ii ◽

Negative Impact ◽

Predictive Biomarkers ◽

Progression Free Survival ◽

Mutation Status ◽

Pik3ca Mutations ◽

First Line Therapy ◽

Randomized Phase Ii ◽

Group B ◽

The Impact

3549 Background: The outcome for mCRC has changed since the introduction of new chemotherapy schedules and targeted therapies, however new predictive biomarkers are needed. bCTCs and BRAF / PIK3CA mutations have been studied as a potential predictive biomarkers. The primary endpoint was progression-free survival (PFS) in pts WT KRAS and <3 bCTCs, according to BRAF/ PIK3CA status. Methods: This is an open, multicentric, randomized phase II trial and included wildtype KRAS mCRC pts (RAS after approval of protocol amendment), younger than ≤70 with <3 bCTCs, ECOG 0-1 and available tissue for molecular analyses. Pts were stratified per number of metastatic organs involved (1 vs >1) and mutation status of BRAF and/or PIK3CA (WT vs MUT) and randomized to group A (FOLFIRI+Bev) or group B (FOLFIRI+Cet). Results: 240 pts (196 WT and 44 MUT: 6 BRAF, 12 PIK3CA and 6 BRAF + PIK3CA) were included. General characteristics per mutation status (WT vs MUT): Mean age (59 vs 61 years), gender (Male/Female 68/32 vs 70/30%), ECOG 0/1 (57/43 vs 66/34%), primary tumor unresected (48 vs 64%), RAS MUT in 12 pts (11 and 1 pts, respectively), previous chemotherapy (12 vs 9%). Overall response rate (ORR) was 52 and 41% in the WT and MUT groups, respectively. PFS and overall survival (OS) are presented in the table. Conclusions: In the low risk mCRC pts according to bCTCs, BRAF and/or PIK3CA MUT have a negative impact in OS and a trend to worse PFS in the ITT population. The impact of treatment is under evaluation and will be provided during the meeting. Clinical trial information: 2012-000840-90. [Table: see text]

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Effect of t(11;14) on outcomes of patients (pts) with newly diagnosed multiple myeloma (NDMM) in the connect MM registry.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8032 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8032-8032 ◽

Cited By ~ 1

Author(s):

Cristina Gasparetto ◽

Sundar Jagannath ◽

Robert M. Rifkin ◽

Brian G. Durie ◽

Mohit Narang ◽

...

Keyword(s):

Progression Free Survival ◽

Induction Treatment ◽

Newly Diagnosed ◽

First Line ◽

Free Survival ◽

Loss To Follow Up ◽

Observational Cohort ◽

The Impact ◽

Clinical Trial Information

8032 Background: The impact of t(11;14) (16%–24% of MM pts) on prognosis is not fully understood. Consensus is lacking on the effects of induction treatment (tx) on outcomes with t(11;14). The Connect MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with NDMM designed to examine real-world diagnostic patterns, treatment (tx) patterns, clinical outcomes, and HRQoL pt-reported outcomes in pts with NDMM. The impact of t(11;14) on tx outcomes are reported. Methods: Analysis included data from pts from 250 community, academic, and government sites in cohort (C) 1 (9/2009–12/2011) and C2 (12/2012–4/2016), who completed first-line (1L; induction) tx and were tested for t(11;14) by FISH or cytogenetics. Primary end points (progression-free survival [PFS] and overall survival [OS]) were measured from start of 1L tx to earliest event (PFS, death or progression; OS, death), loss to follow-up, or data cutoff, adjusted for baseline (BL) risk factors. A sensitivity analysis excluding pts with concomitant cytogenetic abnormalities [del 17p, t(4;14), t(14;16), 1q+] was also performed. Results: By 1/2018, 3011 pts were enrolled; 2938 were treated. Of 1574 enrolled pts tested for t(11;14), 378 were t(11;14)+ and 1196 were t(11;14)−. More pts in C2 vs C1 were t(11;14)+ (60% vs 40%). BL characteristics were similar between groups. t(11;14) status did not affect PFS ( P= NS) or OS ( P= NS; Table). Pts in C1 and C2 received similar 1L txs (IMiD agent + proteasome inhibitor [PI], 30% vs 42%; PI only, 42% vs 43%; IMiD agent only, 17% vs 11%). Results were similar when pts with concomitant abnormalities were excluded. Conclusions: Results of this analysis suggest that t(11;14) does not affect PFS and OS outcomes in NDMM pts. Clinical trial information: NCT01081028. [Table: see text]

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