Non-Clonal Serum Immunoglobulin Free Light Chains (FLC) as Markers of Overall Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3893-3893 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert Kyle ◽  
Jerry A Katzmann ◽  
Dirk Larson ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Function ◽  
Multivariate Analysis ◽  
Binding Site ◽  
Research Funding ◽  
Hazard Ratio ◽  
Excess Risk ◽  
Serum Immunoglobulin ◽  
Reference Ranges ◽  
Risk Of Death

Abstract Abstract 3893 Background: When screening for clonal disease, the kappa (k) to lambda (l) FLC ratio (FLC-R) is employed to correct for both impaired catabolism (renal function) and non-specific production (generalized immune overstimulation). This adjustment makes it possible to identify patients with relative imbalances between k and l levels, which typically qualifies for clonal excess and has been of value in screening for and prognosticating in patients with most clonal plasma cell disorders. We previously performed a population-based study among Olmsted County residents to ascertain the prevalence of monoclonal gammopathy of undetermined significance (MGUS) and light chain MGUS. We hypothesized that by using this cohort, we could identify whether the FLC assay provides information that would be prognostic in a general population of people 50-years and older. Methods: The Olmsted MGUS prevalence cohort was comprised of 21,463 of the 28,038 enumerated individuals over the age of 50 who were living Olmsted between 1/1/95 and 11/21/2003. The final sample size of individuals for the present study was 15839 due to patient losses secondary to blinding, inadequate sample to perform the FLC assay, and known MGUS or LC-MGUS. For the multivariate analyses, another 772 were excluded due lack of coincident creatinine measurement. The FLC measurements were performed using the FLC assay (Binding Site, Birmingham, UK). The respective reference ranges for k FLC and l FLC are 0.33–1.94 mg/dL and 0.57–2.63; therefore, the reference range for the sum of k and l FLC (S FLC) is 0.90–4.57 mg/dL. Survival time was calculated from the time of sample ascertainment. Results: Forty-five percent of the cohort was male. The median age was 63 years (range 50, 109). On univariate analysis, the hazard ratio for death for those patients with the highest decile of S FLC relative to the other 90% of patients in the cohort was 4.3 (95%CI 4.01, 4.62), Figure 1. Because serum immunoglobulin FLC rise with age and with renal insufficiency, a multivariate analysis was performed to exclude the possibility that S FLC was merely a surrogate for these other parameters. Table 1 shows both univariate and multivariate risk for death. With these other variables included, the hazard ratio for death with highest S FLC decile was lower, but remained significant; hazard ratio, 2.0 (95%1.88, 2.2). Conclusions: The finding that S FLC above the normal range (i.e. highest decile) is associated with inferior overall survival among individuals above the age of 50, excluding patients with known MGUS or LC-MGUS, is important and merits further investigation. Although there is an association between S FLC, renal function, gender, and age, excess risk of death still exists after adjusting for these risk factors on multivariate analysis. The mechanism by which S FLC predicts for outcomes is uncertain, but one could postulate that conditions resulting in overactivation of the immune system contributes to excess risk of death. Whether the S FLC adds above and beyond other conventional inflammatory markers like ESR or CRP cannot be determined by the present study, but is worthy of further investigation. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Off Label Use: No FDA approved indication. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Mead:Binding Site: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties.

Sarcomatoid Renal Cell Carcinoma: Biologic Behavior, Prognosis, and Response to Combined Surgical Resection and Immunotherapy

1999 ◽  
Vol 17 (2) ◽  
pp. 523-523 ◽  
Author(s):  
Thomas Cangiano ◽  
Joseph Liao ◽  
John Naitoh ◽  
Frederick Dorey ◽  
Robert Figlin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Median Duration ◽  
Renal Cell ◽  
High Dose ◽  
Risk Of Death

PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2–based therapy (five patients), tumor-infiltrating lymphocyte–based therapy plus IL-2 (nine patients), high-dose IL-2–based therapy (nine patients), dendritic cell vaccine–based therapy (one patient), and interferon alpha–based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or > 50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2–based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.

Comparative effectiveness of first-line nab-paclitaxel versus paclitaxel monotherapy in triple-negative breast cancer

2019 ◽  
Vol 8 (14) ◽  
pp. 1173-1185 ◽  
Author(s):  
Patricia Luhn ◽  
Stephen Y Chui ◽  
“Angela” Fu-Chi Hsieh ◽  
Jingbo Yi ◽  
Almut Mecke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Similar Efficacy ◽  
Hazard Ratio ◽  
First Line ◽  
Risk Of Death ◽  
The Us ◽  
Similar Risk

Aim: This observational study evaluated the effectiveness of nab-paclitaxel versus paclitaxel monotherapy as first-line (1L) treatment for metastatic triple-negative breast cancer (mTNBC). Materials & methods: 200 patients from the US Flatiron Health electronic health record-derived database (mTNBC diagnosis, January 2011–October 2016) who received 1L nab-paclitaxel (n = 105) or paclitaxel (n = 95) monotherapy were included. Overall survival and time to next treatment were evaluated. Results: The adjusted overall survival hazard ratio was 0.98 (95% CI: 0.67–1.44), indicating a similar risk of death between groups. Adjusted time to next treatment hazard ratio was 0.89 (95% confidence interval: 0.62–1.29). Conclusion: Nab-paclitaxel and paclitaxel monotherapy showed similar efficacy, suggesting their interchangeability as 1L treatments for mTNBC.

Major Improvement of Invasive Aspergillosis Outcome Is Not Enough to Improve Overall Survival In Allogeneic Hematopoietic Stem Cell Transplant Recipients: Results From a Single-Center Retrospective Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1244-1244
Author(s):  
Géraldine Salmeron ◽  
Raphaël Porcher ◽  
Anne Bergeron ◽  
Marie Robin ◽  
Regis Peffault de Latour ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
First Line Treatment

Abstract Abstract 1244 Background. Voriconazole (V) treatment has been shown to improve the 12 week (W) survival rate of hematological patients (pts) with invasive aspergillosis (IA), including recipients of allogeneic hematopoietic stem cell transplants (HSCT). We investigated whether this early survival advantage could translate into a significant increase in overall survival. Methods. We retrospectively reviewed all consecutive pts who received a transplant between Sept. 1997 and Dec. 2008 at Saint-Louis Hospital and were diagnosed as having IA. The temporal origin of the study was the date of IA diagnosis for each patient. Factors associated with survival were analyzed using Cox proportional hazard models. Separate models were estimated for survival up to 12 W and for survival between 12 W and 24 months (M) in pts surviving longer than 12 W. The deaths of pts with and without IA were analyzed with a competing risk framework. Cumulative incidence curves were compared using Gray's tests. Results. Our study examined 89 IA pts. The median follow-up was 70 M (range, 11–130 M). Two pts did not receive any antifungal treatment and were excluded from subsequent analyses. Of the 87 pts, 42 received first-line V and 45 primarily received a lipid formulation of amphotericin B (n=25), amphotericin B deoxycholate (n=10), caspofungin (n=8) or itraconazole (n=2). The primary characteristics of pts with IA and their causes of death, separated by V as first-line treatment, are shown in the table below. The median survival was 2.6 M, and the overall survival at 24 M was 19% (95% CI 12–30 M) (see figure). Overall, the survival rates of the two groups were significantly different (P= 0.010). However, the differences in survival were quite dramatic prior to 10 M, whereas both survival curves became very close after one year. At 18 M, the numbers of surviving pts were almost identical in the two groups [19% (95% CI: 11–34%) in pts who did not receive V as first-line treatment vs. 21% (95% CI 11–38%) in pts who did]. Pts who did not receive V as a first-line treatment displayed a higher probability of dying from IA than those who did (P=0.004), whereas opposite results were found for mortality in pts without IA (P=0.006). The 24-M cumulative incidence of death from IA was 47% (95% CI 31–61%) in the no V group and 19% (95% CI 9–33%) in the group treated with V. The 24-M cumulative incidence of death in pts without IA was 4% (95% CI 7–14%) in the no V group and 27% (95% CI 14–42%) in pts treated with V. The probability of death from another cause, with IA, was similar in both groups (29% vs. 36% at 24 M; P=0.46). After adjusting for donor type, conditioning regimen, progressive GVHD at diagnosis of IA and cumulated steroid dose (mg/kg) in the W preceding IA diagnosis, administration of V as first-line treatment was found to decrease the risk of death during the first 12 W by approximately 70% [HR=0.31 (95% CI 0.16–0.60); P=0.0005]. Conversely, analysis of mortality between 12 W and 24 M failed to identify any significant predictor of risk of death; however, only 24 pts died during this period. Conclusions. The finding that first-line treatment with V, which is associated with a tremendous improvement in IA outcome, does not translate into an increase in overall survival (even in the context of early diagnosis) is striking. Diagnosis of IA following HSCT, whatever the outcome, appears to be a strong marker for poor long-term prognosis. Disclosures: Bergeron: Pfizer: Speakers Bureau, none; Merck: Speakers Bureau, none; Schering: Speakers Bureau, none. Sulahian:Pfizer: Research Funding, non; Merck: Research Funding, none. Ribaud:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, none; Schering: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, none; Gilead: Speakers Bureau, none.

Prognostic Impact of Comorbidities In A Cohort of 788 MDS Patients Based On A CIRS-G Derived Score. A MDS Piedmont Registry Prospective Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1729-1729
Author(s):  
Emanuela Messa ◽  
Daniela Gioia ◽  
Claudia Bertassello ◽  
Gianni Ciccone ◽  
Bernardino Allione ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Impact ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Increased Risk ◽  
Risk Patients ◽  
Progression Risk ◽  
Cox Analysis ◽  
Severe Grade

Abstract Abstract 1729 Background: Management of neoplastic patients is strongly influenced by comorbidities, especially in more advanced ages. Due to that, comorbidities evaluation is a critical issue in the global assessment of patients (pts) affected by myelodysplastic syndromes (MDS). Until now, there is no agreement on which comorbidity index (CI) is more suitable in this setting and different CI has been proposed. Recently a new MDS-specific score (MDS-CI) has been published by Della Porta et al., while the majority of CI in use has been developed in geriatric oncology setting. One of the most useful is Cumulative Illness Rating Scale of Geriatrics (CIRS-G). Aim of our study: Aim of our study was to test the usefulness of the conventional and easy to apply CIRS-G score among a cohort of MDS pts enrolled in the MDS Piedmont Registry from 1999 to 2010 in predicting OS and leukemic progression. Materials and methods: 788 patients from the MDS Piedmont Registry with CIRS-G evaluation at diagnosis were included in our statistical analysis. 78% of the patients were low and Int-1 IPSS risk, the remaining 22% were Int-2-high risk. The majority of patients (69%) carried an histological diagnosis of non RAEB MDS according to WHO classification, the remaining 31% were RAEB I-II. Age stratification was as follows: 10% up to 60, 23% from 61 to 70, 43% from 71 to 80, 24% over 80 years. Comorbidities with score up to 2 were considered mild while the ones with values higher than 2 were considered severe. We evaluated the global impairment of each patient creating two comorbidity scores based on the number of mild comorbidities (mild comorbidities score, MCS) and severe comorbidities (severe comorbidities score, SCS). Results: The majority of our patients showed only mild comorbidities and the comorbidities with the greater number of patients carrying severe grade of impairment are the cardiac (25%), hypertensive (30%) and endocrinological (20%) ones. COX analysis did not show an impact of comorbidities on leukemic progression risk while there is a statistically significant impact on overall survival of respiratory, renal, urological and osteo-muscular comorbidities (HR respectively of 1,18; 1,3; 1,3; 1,16). There is a trend of increased risk of non MDS related death in patients with severe grade of each comorbidity. Then we set up a Fine and Gray regression model in order to evaluate the global impact of comorbidities on leukemic progression and overall survival according to SCS and MCS. Neither SCS nor MCS showed an impact on the leukemic progression risk. Considering overall survival (OS), MCS showed a HR of 1,12 (p= 0,009) and moreover SCS has a strong impact on the risk of death (HR 1,59; p= 0,000). MCS remains statistically significant in low IPSS risk patients (p<0,001) while there is no influence of MCS on OS considering high IPSS risk patients (p=0,244). COX analysis stratifying pts for performance status (PS) and age classes confirmed the results obtained in the whole population. We performed a multivariate analysis and confirmed that SCS score (p=0,0006), age and IPSS (all p<0,0001) but not PS (p=0,22) are independent prognostic factors in OS prediction. Conclusions: Our data based on a prospective evaluation of 788 MDS patients enrolled in the MDS Piedmont Registry showed that CIRS-G evaluation is a suitable and easy to apply method useful in patients evaluation at diagnosis and during disease management. In our multivariate analysis IPSS is the most useful tool for leukemic progression evaluation, while SCS score (derived from CIRS-G evaluation) and age are the most important variables able to predict overall survival while PS at diagnosis does not add any useful information for this evaluation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Prognostic Calculator Easix Predicts Acute Gvhd, Non-Relapse Mortality and Overall Survival in Adult Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2069-2069
Author(s):  
Miriam Sanchez-Escamilla ◽  
Patrick Hilden ◽  
Molly Maloy ◽  
Samira A Fatmi ◽  
Doris Ponce ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Acute Gvhd ◽  
Endothelial Damage ◽  
Adult Patients ◽  
Stress Index ◽  
Unrelated Donor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Reduced Intensity

Abstract Keywords Allogeneic transplantation; endothelial damage; biomarkers. Background Endothelial damage is associated with severe complications and increased risk of death after allogeneic hematopoietic cell transplantation (AlloHCT). The recently developed Endothelial Activation and Stress Index (EASIX) is a prognostic tool that uses clinical lab values and has been shown to predict non-relapse mortality (NRM) and overall survival (OS) at onset of acute graft versus host disease (aGVHD) in reduced intensity (RIC) alloHCT (Luft, Lancet Haematol 2017). We hypothesized that EASIX may be valuable for more broadly predicting aGVHD, NRM and OS after AlloHCT, beyond time of onset of aGVHD. Design We evaluated 152 adult patients who received an unmodified RIC AlloHCT from a related or unrelated donor with uniform GVHD prophylaxis of sirolimus/tacrolimus and low-dose MTX for treatment of lymphoid malignancies, between April 2008 and May 2017. The EASIX formula (LDH*Creatinine/platelet counts) was calculated at multiple timepoints (pre-HCT, day 30, day 100, onset TMA and aGVHD). For all EASIX assessments post-HCT, a landmark analysis was conducted at the given timepoint A log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. A one-unit increase in log2 EASIX is associated with a doubling (one-fold increase) of EASIX on the original scale. Kaplan-Meier, cumulative incidence, and cox modeling (cause specific for NRM and aGVHD) were used to evaluate EASIX as it relates to outcomes of interest. Relapse and death or relapse were considered competing risks for NRM and aGVHD respectively. Results The median age at transplant was 54 years (range 23-78), 70% were males, a majority had non-Hodgkin lymphoma (68%), and most had sensitive disease at time of HCT (CR=56%; PR=33%). All patients, except two, received peripheral blood stem cells. Sixty-three patients had an HLA-identical related donor, while the remaining 89 had an unrelated donor transplant (HLA-matched in 75 patients, and HLA-mismatched in 14 patients). HCT-CI was 0 in 49 patients, 1-2 in 41 and ≥ 3 in 62 patients. With a median follow-up in surviving patients of 5.4 years (range, 0.8-10), the 1 and 3 years OS rate was 84.2% (95% CI, 77.3-89.1) and 67.9% (95% CI, 59.6-74.8), respectively. The NRM rate at 1 and 3 years was 7.9% (95% CI, 4.3-12.9) and 16.4% (95% CI, 10.9-22.8), respectively. The 1-year cumulative incidences of grades 1-4, 2-4 and 3-4 aGVHD were 56.6% (95% CI, 48.3-64.1), 42.1% (95% CI, 34.2-49.8) and 7.9% (95% CI, 4.3-12.9), respectively. Post-HCT thrombotic microangiopathy was only observed in 13 patients, representing too few events for EASIX analysis. As expected, HCT-CI was significantly associated with both OS and NRM. Pre-HCT EASIX was significantly associated with increased NRM (HR=1.60 [95% CI, 1.15-2.23], p=0.005) and aGVHD grade 1-4 and 2-4 (HR=1.33 [95% CI, 1.08-1.64], p=0.006 and HR=1.39 [95% CI, 1.10-1.75], p=0.005; respectively), but not OS or grade 3-4 aGVHD (Table 1). EASIX at day 30 and day 100 was significantly associated with both OS and NRM (Figures 1-4). Furthermore, confirming the results of Luft, EASIX calculated at onset of any grade aGVHD was significantly associated with OS (HR=1.34 [1.10-1.63], p=0.004) and NRM (HR=1.47 1.11-1.94], p=0.007). Finally, there was no correlation between HCT-CI and EASIX score. Conclusions We conclude that the EASIX formula, calculated at various timepoints pre and post AlloHCT, is significantly associated with NRM and OS. Pre-HCT EASIX also predicts risk of aGVHD, confirming prior results, EASIX at onset of acute GVHD is a predictor of NRM and OS in adult recipients RIC AlloHCT. EASIX provides an independent and easily accessible tool to predict important AlloHCT outcomes that can be used in addition to HCT-CI to better risk stratify patients. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Perales:Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees; Novartis: Other: Personal fees.

scholarly journals Patient Related Factors Have an Indepedent Impact on Overall Survival in Myelodysplastic Syndrome Patients: A Report of the MDS-Can Registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 165-165
Author(s):  
Rena Buckstein ◽  
Richard A. Wells ◽  
Nancy Zhu ◽  
Thomas J. Nevill ◽  
Heather A Leitch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Physical Performance ◽  
Predictive Factors ◽  
Research Funding ◽  
Performance Tests ◽  
Related Factors ◽  
Risk Of Death ◽  
The Impact ◽  
Very High

Abstract Introduction: MDS is a disease of the elderly; yet, the impact of clinical frailty (an age-related vulnerability state created by a multidimensional loss of reserves) and patient-reported outcomes on overall survival (OS) are unknown. Rockwood et al. have developed a simple 9-point clinical frailty scale (CFS) that correlated highly with the risk of death, institutionalization, worsening health and hospital use (Rockwood K., CMAJ 2005). In a prospective, national MDS registry, participants have undergone annual evaluations with the following: (a) 3 geriatric physical performance tests, (b) Charlson (CCI) and Della Porta comorbidity index (DP-CCI) scores, (c) graded frailty using the Rockwood CFS, (d) disability assessments with the Lawton Brody SIADL, and (e) QOL using the EORTC QLQ C-30 and the EQ-5D. The results of these frailty assessments and the effects of these patient-related factors and reported outcomes on OS, in addition to the IPSS/revised IPSS, will be presented. Methods: Overall survival was measured from time to enrollment. Results from physical performance tests were divided into quintiles with higher scores indicating better performance. We used univariate and multivariable Cox proportional hazard model to determine significant predictive factors of overall survival (OS). The variables considered included age, IPSS, R-IPSS, ferritin, LDH, transfusion dependence, hemoglobin (hgb), ECOG, frailty, CCI and DP-CCI, grip strength, 4 M walk test, stand-sit test, modified short physical performance battery (SPPB), Lawton Brody SIADL, time from diagnosis and selected QOL domains including the EQ-5D summary score, EORTC physical functioning, dyspnea and fatigue scores. Results: 453 MDS patients (pts) have been consented and enrolled locally since January 2008 (n=231) and nationally since January 2012 (n=222). Median time from diagnosis was 5.8 mos (IQR 1.4-21). Median age was 73 y (range, 26-95 y), 65% were male and the R-IPSS scores were very low (14%), low (46%), intermediate (24%), high (10%) and very high (6%). Thirty-three % of pts were transfusion dependent at enrollment. Median CCI and DP-CCI scores were 1 (0-12) and 0 (0-6) respectively with 18% and 24% falling into the highest category scores. Median frailty scale score (n=346) was 3 (1-9) with 25% having scores indicating moderate (4-5) or severe (6-9) frailty. The CCI and DP-CCI strongly correlated (r=0.6; p< .0001) with each other, while frailty significantly but modestly correlated with them (r=0.3-0.35, p<.0001). With a median follow up (from enrollment) of 15 mos (95% CI: 13-16), 159 (35%) pts have died and 28 pts lost to follow up. Actuarial survival was 41.0 mos (range, 33.6 - 48.5 mos). When considering patient related factors - age, frailty, comorbidity (both indices), sex, ECOG, the 10 x stand sit test, the SPPB, Lawton Brody SIADL, and all QOL domains considered above were significantly predictive of OS. The multivariable model with the highest R2 included R-IPSS (p=.0004), frailty (1-3 vs 4-9, p= .004), CCI (0-1 vs >2, p=.03) and EORTC fatigue (p=.01) as summarized in Table 1 below. A frailty score > 3 predicted for worse survival (figure 1: 2 year OS 68.5% vs. 83.8%) and further refined survival within the R-IPSS categories (Figure 2). Frailty was also the single most predictive factor for OS from the start of azacitidine therapy (not shown). Conclusions: Patient-related factors such as frailty and comorbidity (that evaluate physiologic reserve and global fitness) should be considered in addition to traditional MDS prognostic indices. Abstract 165. Table. Independent Covariate Predictive factors at baseline Coefficient SE p -value HR 95% CI of HR R2 (%) Time from diagnosis (months) * 0.0335 0.1076 0.7557 1.034 0.837 1.277 17.29% R-IPSS (5 categories) <.0001 Very high vs. very low 2.5701 0.7289 0.0004 13.066 3.131 54.524 High vs. very low 2.1156 0.6437 0.0010 8.294 2.349 29.285 Intermediate vs. very low 1.0466 0.6430 0.1036 2.848 0.808 10.043 Low vs. very low 0.6346 0.6181 0.3045 1.886 0.562 6.334 Frailty (1-3 vs. 4-9) -0.8323 0.2905 0.0042 0.435 0.246 0.769 Comorbidity Charlson (0-1 vs. ³2) -0.5915 0.2749 0.0314 0.553 0.323 0.949 EORTC fatigue * 0.3671 0.1546 0.0176 1.443 1.066 1.954 natural log-transformation was applied for normalizing distribution Figure 1 Overall survival by Frailty (n=346) Figure 1. Overall survival by Frailty (n=346) Figure 2 Overall Survival by Frailty and R-IPSS Figure 2. Overall Survival by Frailty and R-IPSS Disclosures Buckstein: Celgene Canada: Research Funding. Wells:Celgene: Honoraria, Other, Research Funding; Novartis: Honoraria, Research Funding; Alexion: Honoraria, Research Funding. Leitch:Alexion: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Educational Grant Other, Honoraria, Research Funding. Shamy:Celgene: Honoraria, Other.

scholarly journals Effect of Timing and Duration of Maintenance Lenalidomide in Myeloma Patients after Autologous Stem Cell Transplantations

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 194-194
Author(s):  
Idrees Mian ◽  
Denai Milton ◽  
Uday R. Popat ◽  
Nina Shah ◽  
Yago Nieto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Disease Status ◽  
Hazard Ratio ◽  
P Value ◽  
Free Survival ◽  
Late Initiation

Abstract Introduction: Maintenance lenalidomide after autologous hematopoietic stem cell transplantation (auto HCT) has been shown to improve progression free (PFS) and overall survival (OS) in myeloma patients. In this analysis we sought to determine the impact of lenalidomide treatment on achievement of complete remission (CR), survival and the incidence of secondary primary malignancies (SPM). Methods: We retrospectively analyzed all (N=466) consecutive myeloma patients who underwent auto HCT and received maintenance lenalidomide between August 2006 and September 2013 at our institution. Patients received doses of maintenance lenalidomide ranging from 5 mg – 15 mg/day or every other day. We looked at whether lenalidomide improved disease status, specifically CR in patients who had not achieved this before maintenance initiation and the median time to achieve CR. We also analyzed the effects of early initiation (<4-months after auto HCT) of maintenance lenalidomide versus late initiation (≥ 4-months after auto HCT) with regards to PFS and OS using the Kaplan-Meier method. Lastly we assessed if continuation of maintenance therapy beyond 2 and 3-years after auto HCT improved PFS and OS and increased the incidence of SPM. Results: The median follow-up time for all patients was 26.6 months. 173 patients (37%) experienced improvements in their disease status. Of these, 86 patients (50% of those with noted improvements and 19% of total patients assessed) who were not in CR before maintenance achieved CR while on maintenance. The average time to achieve CR in these patients was 12.9 months. Comparing the patients who were started on early maintenance treatment with those who were started on late maintenance therapy, we did not find any difference with regards to PFS (Hazard Ratio [HR]=0.90; p-value=0.57) and OS (HR=0.90; p-value=0.74). However, patients who had been on lenalidomide for > 2 years experienced a significant benefit in OS compared with those on lenalidomide for ≤ 2 years (HR=0.36; p-value=0.0015), although no difference in PFS was observed between the two cohorts (HR=0.77; p-value=0.18). A similar trend in OS was seen for patients who had been on lenalidomide > 3 years compared with those on maintenance treatment ≤ 3 years, though not statistically significant (HR=0.47; p-value=0.10). Again, no difference in PFS was noted between the two groups. Lastly there were only 12 cases of SPM reported in all patients assessed with no statistically significant association to the duration of lenalidomide use. In all 12 cases, lenalidomide was suspended and the mortality among these patients was 50%. Conclusions: Maintenance lenalidomide improves response rates after auto HCT in some patients including the CR rate, however, the median time to achieve CR in these patients is approximately 13 months. The patients who received maintenance therapy for > 2years had a significantly lower risk of death with a trend of improved OS in patients who continued maintenance therapy beyond 3-years. We conclude that the maintenance therapy should be continued for at least 2 years and possibly longer after auto HCT. Table 1 Summary of Survival Outcomes Maintenance Treatment Initiation Measure Early (N=155) Late (N=184) p-value Progression-free survival Hazard ratio (95% CI)a 0.90 (0.63, 1.30) 0.57 Overall survival Hazard ratio (95% CI)a 0.90 (0.49, 1.66) 0.74 Duration of Maintenance Treatment Measure > 2 years (N=115) ≤ 2 years (N=224) p-value Progression-free survival Hazard ratio (95% CI)b 0.77 (0.52, 1.13) 0.18 Overall survival Hazard ratio (95% CI)b 0.36 (0.19, 0.67) 0.0015 > 3 years (N=49) ≤ 3 years (N=290) p-value Progression-free survival Hazard ratio (95% CI)b 0.75 (0.45, 1.26) 0.28 Overall survival Hazard ratio (95% CI)b 0.47 (0.19, 1.15) 0.10 a Cox proportional hazards regression model: measure included as a baseline covariate with the following additional covariates: patient’s cytogenetic risk, creatinine, hemoglobin, B2-microglobulin, ISS stage at diagnosis, disease status at auto HCT, and response prior to auto HCT. b Cox proportional hazards regression model: measure included as a time-dependent covariate with the covariates listed above. Figure 1 Comparison of Overall Survival in Early vs Late initiation of Revlimid Figure 1. Comparison of Overall Survival in Early vs Late initiation of Revlimid Figure 2 Overall Survival – All Patients Figure 2. Overall Survival – All Patients Disclosures Shah: Novartis: Consultancy, Research Funding; Millennium Pharmaceuticals: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Array: Consultancy, Research Funding. Orlowski:Onyx Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Early T-Cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) Is a High-Risk Subtype in Adults

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1418-1418
Author(s):  
Nitin Jain ◽  
Audrey Lamb ◽  
Susan M. O'Brien ◽  
Farhad Ravandi ◽  
Marina Konopleva ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Research Funding ◽  
Who Classification ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor

Abstract Background: Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is a recently recognized high-risk T-ALL subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we compared the outcomes of adults with ETP-ALL who received treatment on frontline regimens to those of patients with other T-ALL immunophenotypic subtypes. Methods: Patients with newly-diagnosed T-ALL who received frontline chemotherapy between the years 2000 and 2014 at The University of Texas MD Anderson Cancer Center (MDACC) were identified and immunophenotypically categorized into early, thymic, and mature per the European Group for the Immunologic Classification of Leukemia (EGIL)/WHO classification. Patients with ETP-ALL were identified on the basis of the following immunophenotype: CD1a(-), CD8(-), CD5(-/dim), and positivity for one or more stem cell or myeloid antigens. Patients received frontline treatment with the following chemotherapy regimens: hyper-CVAD alone (n=43), hyper-CVAD + nelarabine (n=44) or augmented BFM regimen (n=24). Results: A total of 111 patients with T-ALL with adequate immunophenotype data were identified. There was no difference in the outcomes of patients based on the EGIL/WHO subtypes (Fig 1). A total of 19 patients (17%) had ETP-ALL. The complete remission rate (CR)/CR with incomplete platelet recovery (CRp) rate in patients with ETP-ALL was significantly lower than that of non-ETP-ALL patients (73% vs. 91%; p=0.03). The median overall survival for patients with ETP-ALL was 20 months vs. not reached for the non-ETP-ALL patients (p = 0.008) (Fig 2). ETP-ALL remained a high-risk subgroup within the WHO 'Early' group (Fig 3). A subset of patients with early T-ALL had an immunophenotype that resembled that of ETP-ALL except for having ≥75% CD5 expression (ETP+CD5). The OS of patients with ETP+CD5 (n=19) was similar to that of non-ETP-ALL patients and differed from that of ETP-ALL patients (p=0.059). By univariate analysis, the following variables were significant for survival: age, WBC count (<50 vs. ≥50 x109 /L), platelet count (<100 vs. ≥100 x109 /L), LDH (<600 vs. ≥600 IU/L) and ETP-ALL (Table 1). By multivariate analysis, only age (HR: 2.862; 95%CI: 1.140-7.183; p=0.025) and ETP-ALL (HR: 2.275; 95%CI: 1.117-4.631; p=0.023) were significant. Conclusions: ETP-ALL represents a high-risk disease subtype of adult ALL. Allogeneic stem cell transplant in CR1 should be considered. Novel treatment strategies are needed to improve treatment outcomes in this T-ALL subset. Table 1. Univariate and multivariate analysis for survival Parameter Survival UVA MVA P P HR 95%CI Age ≥60 0.013 0.025 2.862 1.140-7.183 Gender 0.24 - - - Diagnosis (ALL vs. LBL) 0.13 - - - WBC < 50.0 (x 109 /L) 0.009 - - - Hemoglobin <10 (g/dL) 0.36 - - - Platelet <100 (x 109 /L) 0.036 - - - LDH <600 (IU/L) 0.045 - - - CNS involvement at Dx 0.18 - - - WHO classification (early, thymic, mature) 0.101 - - - ETP-ALL 0.008 0.023 2.275 1.117-4.631 Treatment received 0.43 - - - Figure 1. Overall survival of patients with T-ALL (N=111) categorized as Early, Thymic and Mature per EGIL/WHO Classification Figure 1. Overall survival of patients with T-ALL (N=111) categorized as Early, Thymic and Mature per EGIL/WHO Classification Figure 2. Overall survival of patients with ETP-ALL (N=19) compared to non-ETP ALL (N=92) Figure 2. Overall survival of patients with ETP-ALL (N=19) compared to non-ETP ALL (N=92) Figure 3. Overall survival of patients with WHO 'early' subcategorized as ETP vs. non-ETP, WHO 'thymic', and WHO 'mature' (N=111) Figure 3. Overall survival of patients with WHO 'early' subcategorized as ETP vs. non-ETP, WHO 'thymic', and WHO 'mature' (N=111) Disclosures Konopleva: Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Cortes:Astellas: Consultancy, Research Funding; BerGenBio AS: Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Teva: Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

scholarly journals Survival Outcome of Patients with Acute Myeloid Leukemia Transformed from Myeloproliferative Neoplasms

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1940-1940 ◽  
Author(s):  
Dai Chihara ◽  
Hagop M. Kantarjian ◽  
Kate J Newberry ◽  
Farhad Ravandi ◽  
Naval G. Daver ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Treatment Strategies ◽  
Survival Outcome ◽  
Hazard Ratio ◽  
Complex Karyotype ◽  
Acute Myeloid

Abstract Purpose: Progression to acute myeloid leukemia (AML) from myeloproliferative neoplasms (MPNs) is almost always fatal. To explore the best treatment strategies for this serious complication, we analyzed the survival outcome of patients with MPNs who progressed to AML based on treatment received at our institution. Patients and Methods: A total of 273 patients who were diagnosed with AML secondary to MPNs between 1989 and 2016 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were calculated. Results: The patients progressed to AML from essential thrombocythemia (ET, N=60), polycythemia vera (PV, N=49), primary myelofibrosis (PMF, N=105), post-ET/PV MF (N=37), and MPN-unclassifiable (N=22). The median age of the patients was 67 (range: 28-92). The median time to AML transformation from MPN diagnosis was 64.5 months (range: 0.9-477.7 months). Complex karyotype was seen in 99 patients at the time of transformation (38%). With a median follow up of 16.5 months (range: 2.7-115.7 months), 247 patients had died (88% from AML, 6% from treatment-related mortality, 6% with other cause including infection and GVHD). Ninety-nine patients received hypomethylating including agent (HMA), 71 a high-dose cytarabine regimen, 52 a low-dose cytarabine regimen, 28 other treatments, and 24 patients did not receive any treatment due deterioration of the patientfs condition or patientfs decision. The median PFS and OS after progression to AML were 2.6 months and 7.0 months, respectively. There was no significant improvement in PFS and OS by date of diagnosis (1989 to 2016). Also, complete response (CR) rate and survival outcome were not significantly different by type of treatment (Figure A) or prior MPN subtype. Overall, 46 patients (27 in CR, 14 not in CR, 4 unknown due to the transplant outside) proceeded to allogeneic transplant (allo-SCT), and the median overall survival after transplant was 15.3 months (6.1-29.4 months). Although it was not statistically significant, patients who achieved a CR before allo-SCT had longer OS than those who received allo-SCT without achieving a CR (35.1 vs 8.9 months; Figure B). Complex karyotype was associated with both shorter PFS (Hazard ratio: 2.2, 95%CI: 1.6-2.9) and OS (Hazard ratio: 2.0, 95%CI: 1.5-2.6). Summary: Survival outcome for AML secondary to MPN remains very poor, and there has been no improvement in survival outcome since 1989. Further studies are urgently needed to test new treatment strategies and to detect residual disease post allo-SCT. Considering dismal outcome after transformation, studies are also needed to explore strategies to prevent this fatal complication. Disclosures DiNardo: Daiichi Sankyo: Research Funding; Abbvie: Research Funding; Agios: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Correlation of HuR cytoplasmic expression in pancreatic cancer and overall patient survival when treated with gemcitabine in the adjuvant setting

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11097-11097 ◽  
Author(s):  
J. Brody ◽  
A. Dasgupta ◽  
C. L. Costantino ◽  
E. Kennedy ◽  
C. J. Yeo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Treatment Strategies ◽  
Hazard Ratio ◽  
Metabolic Enzyme ◽  
Expression Levels ◽  
Risk Of Death

11097 Background:The Hu/ELAV mRNA binding protein HuR is normally localized to the nucleus and is activated upon stress. Previously, we observed that HuR expression is predominantly cytoplasmic in aggressive forms of pancreatic ductal adenocarcinomas (PDA). Additionally, we have shown that overexpression of HuR in pancreatic cancer cell lines renders them hypersensitive to gemcitabine (GEM). GEM is the standard first line therapy used against PDA. This study was designed to determine the relationship between endogenous HuR expression levels and patient outcome. Methods: We analyzed tissue from 29 resected PDA patients who did not receive neoadjuvant therapy. We determined the intensity of cytoplasmic HuR expression. All patients received adjuvant GEM, alone or in combination with radiation therapy or other chemotherapeutics. Correlation between HuR expression levels and overall survival was evaluated. Results: The median overall survival was 20.6 months, with 18 deaths observed. Median overall survival for low HuR expression was 15.3 months. Median overall survival for high HuR expression was not reached at a follow up of 40 months. A univariate Cox regression model gives a hazard ratio of low to high HuR of 3.36 (p=0.025) [95% CI 1.09–10.35]. Adjusting for age, sex, and radiation therapy in this patient group gives an adjusted hazard ratio of 5.04 (p = 0.03) [95% CI 1.15–22.02]. This indicates a 5-fold increase in risk of death in patients with low HuR levels compared to high HuR levels among patients receiving GEM. Conclusions: This is the first report of a correlation between levels of cytoplasmic HuR expression and overall survival in GEM treated patients. Together with our previously reported experimental data, HuR is regulating the key metabolic enzyme for GEM activation (deoxycytidine kinase). Therefore, HuR is a marker for therapeutic efficacy of GEM based regimens and is a candidate target for the optimization of GEM based treatment strategies. [Table: see text] No significant financial relationships to disclose.

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