Predictors of hypomethylating agent discontinuation among patients with higher-risk myelodysplastic syndromes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7043-7043
Author(s):  
Amer Methqal Zeidan ◽  
Namita Joshi ◽  
Hrishikesh Kale ◽  
Wei-Jhih Wang ◽  
Shelby Corman ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Real World ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Poor Performance ◽  
Risk Groups ◽  
Refractory Anemia ◽  
Poor Performance Status ◽  
Related Factors

7043 Background: Real-world studies have shown that persistence with intravenous (IV) and subcutaneous (SC) hypomethylating agents (HMAs) among patients (pts) with higher-risk myelodysplastic syndromes (MDS) is poor, with over one-third of treated pts receiving <4 cycles or having a ≥90-day gap in therapy, despite recommendations for at least 4-6 cycles to elicit response in absence of progression/unacceptable toxicity. Survival outcomes have also been shown to be worse, and direct medical costs higher, among HMA non-persistent vs persistent pts. We explored factors associated with early discontinuation of HMA therapy in this population. Methods: This was a retrospective cohort study among pts from the 2010-2016 SEER-Medicare linked database with a diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) from 2011-2015. Included pts had to have received HMA therapy and have ≥12 months’ continuous follow-up after diagnosis. Discontinuation was defined as stopping HMA therapy before 4 cycles. Multivariable logistic regression was used to assess predictors of HMA discontinuation. Results: In total, 664 pts with RAEB and treated with HMAs were included. Overall, 193 (29%) discontinued before 4 cycles; of these, 91 (47%) discontinued after 1 cycle, 57 (30%) 2 cycles, and 45 (23%) 3 cycles. Compared with pts continuing for ≥4 cycles, pts discontinuing before 4 cycles were generally older and more likely to be single/separated/divorced/widowed, have more comorbidities, and have poor performance status (PS) (Table). These trends were most pronounced among pts discontinuing HMA therapy after only 1 cycle vs ≥4 cycles (Table). In multivariable analysis, age 71-75 vs ≥80 y (odds ratio [OR] 0.556, p=0.017) and poor PS (OR 1.585, p=0.019) remained significant predictors of HMA discontinuation. Among treatment-related factors, the most statistically significant association with HMA discontinuation was observed for GCSF use (OR 0.453, p<0.001). Number of pills/day was not a predictor of HMA discontinuation (OR 1.009, p=NS). Conclusions: In this real-world study, almost one-third of RAEB pts treated with IV/SC HMAs discontinued before 4 cycles, with almost half of these pts discontinuing after only 1 cycle. Predictors of HMA discontinuation included older age and poor PS. Novel approaches are needed to improve persistence with HMA therapy, particularly among these higher-risk groups.[Table: see text]

Should all patients (pts) with advanced biliary cancers receive first-line treatment with cisplatin and gemcitabine (GC)?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 244-244
Author(s):  
Vanessa Costa Miranda ◽  
Luiza Dib-Faria ◽  
Maria Ignez Freitas Melro Braghiroli ◽  
Jorge Sabbaga ◽  
Daniel Fernandes Saragiotto ◽  
...  
Keyword(s):  
Median Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Poor Performance ◽  
Median Number ◽  
Poor Performance Status ◽  
Poor Survival ◽  
First Line ◽  
Dismal Prognosis

244 Background: GC is considered the standard of care for pts with advanced biliary tract cancer (BTC), providing median survival of nearly one year. (Valle J et al. NEJM 2010) Nevertheless, many pts experience poor outcomes, leading to a growing interest to identify pts who might benefit from such treatment. Here we aimed to investigate clinical and laboratory factors associated with poor survival among BTC pts treated with GC. Methods: We retrospectively evaluated all consecutive pts with advanced/metastatic BTC who received first line GC at the Instituto do Cancer do Estado de Sao Paulo, Brazil, in a 2 year-period. Clinical and laboratory variables that could influence pts’ outcomes were gathered from medical charts. Cox regression proportional hazard model was used to investigate the following prognostic factors for death: pre-treatment biliary deobstruction, baseline Ca 19.9, any GC interruptions or dose reductions, baseline ECOG status, Charlson Comorbidity Index (CCI) and age. P values < 0.05 in multivariable analysis were considered significant. Results: From January/2009 to July/2011, 72 pts were identified. The median age was 60 years (range 30-80 years), 45 pts (62.5%) were female and 50 (69.4%) presented baseline ECOG 0-1. The median number of cycles of CG was 4 (range 1-9). Grade 3 /4 neutropenia and thrombocytopenia occurred in 16.6% and 12.5% of pts, respectively. Median survival of the whole cohort was 9.53 months (95% CI: 6.2 - 11.4). Median survival in pts with ECOG 0/1 was 13.5 months (95% CI: 9,5 – NR) and among pts with ECOG 2/3 3,5 months (95% CI: 1-7). In the Cox multivariable model, ECOG 2 /3 versus 0/1 (HR: 8.4, 95% CI: 3.4 to 20.7; p<0.001) and CCI score ≥ 2 (HR: 9.5 95% CI: 1.6 to 55.3; p= 0.012) significantly predicted for poor survival. There was a trend for improved survival among pts who had biliary drainage before starting GC (HR: 2.3 95% CI: 1.0 - 5.3; p= 0.051). Conclusions: In this retrospective cohort of unselected pts with advanced BTC treated with first line GC, poor performance status and multiple comorbid illnesses were associated with dismal prognosis. Treatment with GC should be carefully discussed before being offered to these pts.

Trends in checkpoint inhibitor therapy for advanced urothelial cell carcinoma (aUC) at the end of life: Insights from real-world practice.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Ravi Bharat Parikh ◽  
Matt D. Galsky ◽  
Bishal Gyawali ◽  
Fauzia Riaz ◽  
Tara Laura Kaufmann ◽  
...  
Keyword(s):  
End Of Life ◽  
Real World ◽  
Systemic Therapy ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Nonparametric Tests ◽  
Poor Performance Status ◽  
National Guidelines ◽  
Health Database

395 Background: National guidelines recommend against chemotherapy use at the end of life. Five CPIs are now approved for aUC. We hypothesized that oncologists may have a lower threshold to initiate CPI in patients (pts) at the end of life, particularly among pts with poor performance status (PS), because of the perceived favorable toxicity profile of CPI. Methods: We conducted a secular trend analysis using the Flatiron Health Database, a large real-world electronic medical record-derived dataset. We used nonparametric tests of trend (p values reported as ptrend) to evaluate quarterly proportions of pts initiating CPI, chemotherapy, or no systemic therapy within 30 and 60 days of death, among 2959 pts diagnosed with aUC from 2015 to 2017. Results: 1637 pts died during follow-up and were eligible for analysis. 278 (17.0%) and 488 (29.8%) pts initiated a new line of systemic therapy in the last 30 and 60 days of life, respectively. The quarterly proportion of CPI initiators within 60 days of death increased from 1.0% to 23% during the study period ( ptrend < 0.001), with corresponding decreases in chemotherapy initiation and no systemic therapy. After CPI approval in mid-2016, CPI initiation significantly increased among pts with Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 ( ptrend = 0.02) but did not significantly change among pts with PS 0-1. Initiation of any systemic therapy at the end of life doubled (17.4% to 34.8%) over the study period, driven largely by end-of-life CPI use. Compared to chemotherapy initiators, CPI initiators had slightly worse PS (table). Conclusions: In patients with aUC, there has been a dramatic rise in CPI initiation at the end of life particularly among pts with poor PS. Existing guidelines on systemic therapy initiation near the end of life should account for the increasing use of CPI. [Table: see text]

scholarly journals Real world clinical outcomes of adjuvant sequential chemoradiation in patients with gallbladder carcinomas with poor performance status

2020 ◽  
Vol 38 (4) ◽  
pp. 262-269
Author(s):  
Rakesh Kapoor ◽  
Kannan Periasamy ◽  
Rajesh Gupta ◽  
Arun Yadav ◽  
Divya Khosla
Keyword(s):  
Clinical Outcomes ◽  
Real World ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status

Palliative electrochemotherapy in primary or recurrent vulvar cancer

2020 ◽  
Vol 30 (7) ◽  
pp. 927-931 ◽  
Author(s):  
Giacomo Corrado ◽  
Giuseppe Cutillo ◽  
Simona Maria Fragomeni ◽  
Valentina Bruno ◽  
Luca Tagliaferri ◽  
...  
Keyword(s):  
Palliative Treatment ◽  
Pulse Generator ◽  
Vulvar Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Poor Performance ◽  
Median Number ◽  
Poor Performance Status ◽  
Electrical Pulses

ObjectiveSince vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer.MethodsData were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer.ResultsA total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3–42) and median operative time was 13 (range 7–20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up.ConclusionsElectrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

scholarly journals Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet

Blood ◽  
2013 ◽  
Vol 122 (17) ◽  
pp. 2943-2964 ◽  
Author(s):  
Luca Malcovati ◽  
Eva Hellström-Lindberg ◽  
David Bowen ◽  
Lionel Adès ◽  
Jaroslav Cermak ◽  
...  
Keyword(s):  
Performance Status ◽  
Development Program ◽  
Poor Performance ◽  
World Health ◽  
Individual Risk ◽  
Poor Performance Status ◽  
Level Of Evidence ◽  
Related Factors ◽  
Health Organization

Abstract Within the myelodysplastic syndrome (MDS) work package of the European LeukemiaNet, an Expert Panel was selected according to the framework elements of the National Institutes of Health Consensus Development Program. A systematic review of the literature was performed that included indexed original papers, indexed reviews and educational papers, and abstracts of conference proceedings. Guidelines were developed on the basis of a list of patient- and therapy-oriented questions, and recommendations were formulated and ranked according to the supporting level of evidence. MDSs should be classified according to the 2008 World Health Organization criteria. An accurate risk assessment requires the evaluation of not only disease-related factors but also of those related to extrahematologic comorbidity. The assessment of individual risk enables the identification of fit patients with a poor prognosis who are candidates for up-front intensive treatments, primarily allogeneic stem cell transplantation. A high proportion of MDS patients are not eligible for potentially curative treatment because of advanced age and/or clinically relevant comorbidities and poor performance status. In these patients, the therapeutic intervention is aimed at preventing cytopenia-related morbidity and preserving quality of life. A number of new agents are being developed for which the available evidence is not sufficient to recommend routine use. The inclusion of patients into prospective clinical trials is strongly recommended.

scholarly journals “IDENTIFYING HIGH-RISK CHRONIC LYMPHOCYTIC LEUKEMIA: A PATHOGENESIS-ORIENTED APPRAISAL OF PROGNOSTIC AND PREDICTIVE FACTORS IN PATIENTS TREATED WITH CHEMOTHERAPY WITH OR WITHOUT IMMUNOTHERAPY.”

2016 ◽  
Vol 8 ◽  
pp. 2016047 ◽  
Author(s):  
Sara Martinelli ◽  
Antonio Cuneo ◽  
Gian Matteo Rigolin
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Poor Performance ◽  
High Serum ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Poor Performance Status

 Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment is important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS), response to treatment and transformation into Richter’s syndrome (RS). We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our stringent criteria no parameter was found to independently predict for inferior response to treatment or development of RS.  

scholarly journals Prognostic irrelevance of ring sideroblast percentage in World Health Organization–defined myelodysplastic syndromes without excess blasts

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5674-5677 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
Curtis A. Hanson ◽  
Nanna H. Sulai ◽  
Janice M. Hodnefield ◽  
Ryan A. Knudson ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Multivariable Analysis ◽  
World Health ◽  
Refractory Anemia ◽  
Idh Mutations ◽  
Ring Sideroblasts ◽  
Transfusion Dependency ◽  
Health Organization ◽  
The Impact

Abstract The presence of ≥ 15% bone marrow (BM) ring sideroblasts (RS) and < 5% blasts is required for a diagnosis of refractory anemia with ring sideroblasts. We examined the phenotypic and prognostic relevance of this “15%” RS threshold in 200 patients with myelodysplastic syndromes (MDS) without excess blasts and with ≥ 1% RS. The impact of RS% was assessed both as a continuous and categorical variable: < 5% (n = 56), 5%-14% (n = 32), 15%-50% (n = 79), and > 50% (n = 33). RS% correlated (P < .05) directly with age, platelet count, transfusion dependency, BM cellularity, and mutant SF3B1 and inversely with hemoglobin level, multilineage dysplasia, and high-risk karyotype; but did not correlate with IDH mutations. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Neither univariate nor multivariable analysis showed significant effect for RS% on overall or leukemia-free survival, suggesting the limited prognostic value of quantifying BM RS in MDS.

scholarly journals Multiple Myeloma Therapy in Tawam Hospital. First Report from United Arab Emirates (UAE)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5652-5652
Author(s):  
Arif Alam ◽  
Khaled al Qawasmeh ◽  
Maria Aamir ◽  
Philip L. McCarthy
Keyword(s):  
Plasma Cell ◽  
Induction Therapy ◽  
Response Rate ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Cell Leukemia ◽  
Plasma Cell Disorders ◽  
Lost To Follow Up

Abstract Introduction: Plasma cell disorders are a heterogeneous group of disease ranging from Monocloncal gammopathy of unknown significance to Multiple myeloma (MM) and the highly lethal plasma cell leukemia. The prognosis and therapy of MM has been revolutionized in the past two decades with the introduction of proteasome inhibitors, immunomodulatory drugs (IMiDs) and the monoclonal antibodies. The standard of care for induction has been become a triplet regimen lately. Here we describe our experience with the management of MM patients. Methods: This is a retrospective analysis of Thirty-five patients who were seen with diagnosis with plasma cell disorders from January 1, 2016 till June 30th 2018 at our center in the UAE. Patients with solitary plasmacytoma and plasma cell leukemia were excluded from further analysis (N=3). Thirty-two patients were included in the analysis. Results: The median age was 58 years (range 26 to 94 years). Male to female ratio was 3:1. Biochemical classification showed ten patients with light chain disease only. Twelve patients had IgG kappa disease, eight had IgG lambda while there was one with IgA lambda disease and one was non-secretory with diffuse plasmacytomas. ISS staging (based on albumin and Beta 2 microglobulin) showed ISS stage 1=7, ISS stage 2= 13, ISS stage 3=8 and data was not available for four patients (diagnosed elsewhere). Cytogenetic risk stratification was not possible due to lack of access to interphase FISH. Seven patients did not receive any therapy either due to refusal for further investigation and therapy or poor performance status and comorbidities. Four of these seven have expired while the other three have been lost to follow-up. Twenty-four patients were given induction therapy with a Bortezomib (V)-based regimen while one received IMIDs-based treatment. Regimens and patient numbers are as follows: RVd (Lenalidomide/V/dexamethasone) (N=16), PVd (pomalidomide instead of R due to renal insufficiency) (N=1), V/thalidomide (T) (N=1), VCd (N=2; one for secondary amyloidosis) and Vd (N=4) (poor performance status and/or comorbidities). All patients were given zoledronic acid as well as herpes zoster prophylaxis. Venous thromboembolism (VTE) prophylaxis was prescribed based on published guidelines. Response evaluation was performed in patients receiving at least four cycles of therapy: CR(N=7); Very Good Partial Remission (VGPR) (N=6); Partial Response (PR) (N=5) and not evaluable for response due to lack of data (N=7). Five patients were documented to have received autologous stem cell transplant (autoSCT). Seven patients, lost to follow up after induction presumably received an autoSCT. Conclusion: This is the first report on the management of MM patients in UAE. With a median follow-up of 216 days (range 3 to 839 days) the response rate to induction therapy was 72% (CR+ VGPR). We are unable to report progression free survival due to short follow-up. This response rate of 72% (VGPR or better) is less than the reported in the literature. This may partly be due to lack of patient data regarding induction therapy elsewhere, the use of double over triplet regimens and the absence of autoSCT facilities. Outcome measurement is a difficult task due to tendency of local citizens to travel outside UAE for treatment and the transient nature of the large expatriate population (88% of the total population of approximately 5.4 million) We are working on developing an infrastructure for consistent testing (CD138-selected FISH, consistent staging, use of PET-CT and bone marrow MRI as well as developing auto SCT facilities). We have formulated a uniform treatment plan based on weekly RVd based therapy for 16 weeks as induction followed by recommendation for Auto SCT. If auto SCT is not possible then patients will continue RVd therapy for a total of 12 cycles followed by maintenance lenalidomide till progression. The standardization of diagnosis, therapeutic approach and follow-up should optimize the care and outcomes of UAE MM patients. Disclosures McCarthy: Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

Effect of first-line pembrolizumab treatment in individuals with advanced non-small cell lung cancer and poor performance status.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18796-e18796
Author(s):  
Rajwanth Veluswamy ◽  
Jiayi Ji ◽  
Liangyuan Hu ◽  
Xiaoliang Wang ◽  
Cardinale B. Smith ◽  
...  
Keyword(s):  
Treatment Group ◽  
Real World ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Poor Performance ◽  
Smoking History ◽  
Poor Performance Status ◽  
First Line ◽  
Inverse Probability ◽  
Ecog Ps

e18796 Background: There is limited evidence supporting the optimal use of immune checkpoint inhibitors (ICIs) in NSCLC patients with poor performance status (PS), as clinical trials exclude these patients. In this study, we use real-world oncology data to determine the impact of first line pembrolizumab vs. no treatment in high PD(L)-1 expressing cancers in individuals with advanced NSCLC and ECOG PS ≥2. Methods: We performed a retrospective cohort study of patients with advanced NSCLC with ECOG PS ≥2 between 09/01/2014 and 02/18/2020, using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients were included if they were PD(L)-1 high (≥50%) and had clinical and treatment information recorded within 90 days of diagnosis. Real-world overall survival (rwOS) was defined as time from diagnosis to death (censored at last EHR activity). Median rwOS was estimated using weighted Kaplan-Meier methods. A marginal Cox structural model with inverse probability of treatment weighting was used to adjust for selection bias and estimate the effectiveness of pembrolizumab. The inverse probability weights were estimated using an ensemble machine learning technique, Super Learner, based on age, gender, race, practice type and smoking history. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Stratified analysis was conducted by ECOG PS (2 vs >2). Results: 217 (16%) individuals with advanced NSCLC and high PD(L)-1 expression received no treatment, compared to 546 (39%) individuals who received 1L pembrolizumab. The no-treatment group had a lower proportion of ECOG 2 compared to the pembrolizumab group (Table). Median rwOS in the no-treatment group was 2.4 months, compared to 7.1 months in the pembrolizumab group (p<0.001). In unadjusted survival analyses in the entire cohort and in cohorts stratified by ECOG status, treatment with pembrolizumab was associated with a significantly lower risk of death (hazard ratio [HR]: 0.38, 95% Confidence Interval [CI]: 0.31-0.45). In adjusted analyses, individuals treated with pembrolizumab had improved survival (HR: 0.40, 95% CI: 0.35-0.45). Conclusions: Our analysis of real-world clinical oncology data demonstrated that 1L treatment with pembrolizumab was associated with significantly improved rwOS among individuals with ECOG ≥ 2. [Table: see text]

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