Is Renal Impairment Still a Poor Prognostic Marker in Myeloma Care?: A Population Based Study Including 1542 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5033-5033
Author(s):  
Katarina Uttervall ◽  
Johan Andreasson ◽  
Johan Liwing ◽  
Per Näsman ◽  
Johan Aschan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Impairment ◽  
Prognostic Marker ◽  
Control Group ◽  
Line Treatment ◽  
Employment Equity ◽  
Significant Difference ◽  
Study Population ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 5033 Background: Renal impairment (RI) is a relatively common feature of multiple myeloma (MM) and it has been shown in several studies that RI at diagnosis correlates to inferior survival, significant morbidity and increased early death rate. Aims: To understand the impact of RI on survival in the era of novel agents and to evaluate the efficacy of bortezomib-based treatment in patients presenting with RI. The primary endpoint of the study was overall survival (OS) in the whole population and renal response (RR) in 1st, 2nd and 3rd line treatment in a selected center (Karolinska). Time to progression (TTP), time to next treatment (TTNT), overall survival (OS) and MM response were the secondary endpoints. Methods: The study population included all patients diagnosed with MM since earliest January 2000 until latest June 2011 at 6 university clinics, 3 regional centers and 4 local hospitals in Sweden. A S-Creatinine limit of 177 μmol/L was chosen as cutoff for OS calculations. For a detailed analysis on RR all patients with MM with a S-Creatinine >=130 μmol/L that were diagnosed in clinical practice between January 2000 and July 2010 at Karolinska Huddinge and between January 2005 and July 2010 at Karolinska Solna were selected. This S-Creatinine limit was selected in an attempt to cover all MM patients with GFR <50 mL/min. The study population was divided into those receiving bortezomib and those receiving other drug combinations (control group). Results: The population consisted of 1642 patients, but S-Creatinine values were missing for 100 patients resulting in a study population of 1542 patients. Patients with S-Creatinine >=177 μmol/L (n=267) had a significantly worse median OS of 1. 9 years 95% CI[1. 5;2. 6] compared to S-Creatinine <177 μmol/L (n=1275), with a median OS of 4. 1 years 95% CI[3. 8;4. 4]; (p=<0. 001). Patients with >=177 in S-Creatinine receiving bortezomib (n=60) had a median OS of 2. 6 years compared to 1. 7 years in the control group (n=206) (p=0. 05). Of the 1542 patients, 556 were diagnosed and treated at our center. Ninety-five of these patients had a S-Creatinine >=130 μmol/L at diagnosis. Of the 95 patients 52 also had RI in 2nd line and 25 in 3rd line treatment resulting in a total of 172 treatment occasions where anti-myeloma treatment was given to patients with RI. There was no significant difference regarding age, sex, hemoglobin, β2-microglobulin, calcium, or albumin between the bortezomib-group and the control group. In the bortezomib-group, in 1st line treatment, 11 of 12 patients (92%) improved their GFR compared to 57 of 83 (69%) in the control group (p=0. 049). In the 2nd and 3rd treatment line the overall RR was 19% and 43% in the bortezomib treated compared to 23% and 28% in the control group (p=0. 749, and p=0. 257). When analyzing all treatment lines together the MM response was better in the bortezomib-group with significantly higher overall response rate of 80%, compared to 55% (p=0. 026). Median TTP in 1st, 2nd and 3rd line in the bortezomib-group was 18, 6 and 10 months and in the control group 11, 10 and 8 months. Median survival time was 3. 4 years for the control group, whereas 62% of the bortezomib treated patients still were alive at median time of follow up. Conclusion: RI is still an important prognostic marker in MM despite modern treatment with a proteasome inhibitor. Bortezomib-based regimens can partly overcome the negative impact of RI by a higher frequency of RR and MM responses, as well as an improved median OS in comparison to other treatment regimens for MM patients with RI. Disclosures: Liwing: Janssen-Cilag: Employment, Equity Ownership. Näsman:Janssen-Cilag: Consultancy. Aschan:Janssen-Cilag: Employment, Equity Ownership.

Effects of Renal Function on the Pharmacokinetics of Panobinostat in Patients with Advanced Cancer: A Phase I Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5001-5001
Author(s):  
Sunil Sharma ◽  
Emile Voest ◽  
Nicole Hagner ◽  
P.O. Witteveen ◽  
Martijn Lolkema ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Advanced Cancer ◽  
Primary Study ◽  
Control Group ◽  
Maximum Plasma ◽  
Employment Equity ◽  
Study Objective ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 5001 Panobinostat is a potent class I/II/IV oral pan-deacetylase inhibitor which has shown promising clinical activity in patients with multiple myeloma and myelofibrosis, some with compromised renal and hepatic functions. The metabolism mediated by cytochrome P450 3A4 (CYP3A4) and non-CYP pathways is the major clearance pathway of panobinostat, with drug and metabolites being excreted in nearly similar amounts by liver/bile (54.3) and kidneys (40.6). However, the effects of impaired renal and hepatic function on panobinostat pharmacokinetics (PK) have not been elucidated. This study was designed to assess the impact of renal dysfunction on the PK and safety of panobinostat when compared to that of patients with normal renal function. Patients with advanced cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2, AST/ALT 2.5 ULN, normal bone marrow, and varying degrees of renal function were enrolled. Renal function was categorized as normal (as control), mild, moderate, or severe according to baseline 24-hour urine creatinine clearance (CrCL). Serial blood and urine panobinostat samples collected up to 96 and 24 hours, respectively, following a single PK test dose of 30 mg panobinostat were assessed for plasma and urine concentrations by liquid chromatography tandem mass spectrometry. PK parameters were derived from individual plasma or urine concentrationtime data using non-compartmental analysis. The following week, patients continued to receive panobinostat 30 mg orally 3 times a week. Dose was modified according to tolerability. PK results from 19 patients (15 male, 4 female) in this ongoing study are tabulated below. Median age was 66 years, and 13/19 patients had ECOG PS 1. Safety results were available in 18 patients. The most frequent drug-related adverse events (AEs) were grade (Gr) 34 thrombocytopenia in 7 patients (2 normal, 2 mild, 3 moderate) and Gr 3 fatigue in 5 patients (1 normal, 1 mild, 3 moderate). Other drug-related Gr 3 AEs included nausea, diarrhea, and hyperphosphatemia (1 normal patient each); asthenia and anemia (1 mild patient each); and ventricular bigeminy and dehydration (1 moderate patient). Two deaths on therapy not suspected to be study drugrelated occurred in the normal group. Although efficacy is not the primary study objective, PR was noted in 1 moderate patient with bladder cancer while SD was noted in 5 patients (2 pancreatic, 1 ovarian, 1 bladder and 1 renal cancer) as best overall response in these heavily pre-treated patients. The currently available results unexpectedly showed that patients with renal dysfunction did not have higher panobinostat exposures than the control group and the PK of panobinostat did not seem to have a distinct rank-order relationship with the severity of renal dysfunctionPK parameters median rangeRenal Function ClassificationNormal n7(CrCL 80 mL/min)Mild n6(50 CrCL 80 mL/min)Moderate n6(30 CrCL 50 mL/min)Tmax (hr)1.0 0.5-41.0 0.5-41.0 0.5-2Cmax (ng/mL)36.7 30.0-107.014.4 5.8-33.522.8 9.5-52.3AUC0-inf (nghr/mL)371 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{180}{441}\) \end{document}108 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{76}{234}\) \end{document}202 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{78}{329}\) \end{document}t1/2(hr)32.9 25.2-42.836.0 23.7-55.634.3 31.4-35.4ClR/F (L/hr)1.6 0.4-2.71.4 0.5-2.82.1 0.2-3.8Xu0-24hr ( of dose)1.8 1.2-4.00.6 0.2-1.30.7 0.2-1.9 AUC0-inf, area under the concentration-time curve from zero to infinity; Cmax, maximum concentration; t1/2, half-life; Tmax, time to maximum plasma concentration; Xu0-24h, percentage of drug excreted in urine; ClR/F, apparent renal clearance. Disclosures: Sharma: Novartis: Research Funding. Valera:Novartis Pharmaceuticals: Employment. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Mires:Novartis Pharmaceuticals: Employment. Porro:Novaratis Pharma AG: Employment. Woo:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Hess:Novartis: Equity Ownership.

Combinatorial Effect of HDAC6i and Ibrutinib Therapy in CLL Murine Model

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2035-2035
Author(s):  
Kamira Karen Maharaj ◽  
John J. Powers ◽  
Susan Deng ◽  
Alex Achille ◽  
Mibel Pabon-Saldana ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cells ◽  
Cell Lines ◽  
Adoptive Transfer ◽  
Single Agent ◽  
Tumor Burden ◽  
Employment Equity ◽  
Bcr Signaling ◽  
Equity Ownership ◽  
The Impact

Abstract Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor is now FDA approved for front line and relapsed and refractory CLL. Although this drug has been shown to be successful in controlling the disease, most patients only reach partial responses (PR) likely secondary to activation of alternative and redundant BCR signaling pathways. In the past several years, epigenetic changes in CLL have gained special attention (Tong et al 2010) because of their intricate interplay with previously described genetic events and its active role in the regulation of pathogenesis and immune-related pathways (Stilgenbauer et al 2002). Recent publications have described the differential expression of specific HDACs in CLL, as well as the impact of global histone deacetylase activity and its relation with progression and overall survival (Van Damme et al 2014, Yang et al 2015). Previously, we had reported that expression of HDAC6 is increased in CLL patient samples and cell lines. We have also demonstrated that modulation of this HDAC, effects cell proliferation and viability in CLL cell lines. Additionally, treatment with HDAC6i (ACY-738 - a potent and selective HDAC6i) demonstrated increased overall survival in euTCL1 mice, a murine CLL model. Treatment of euTCL1 mice (both adoptive transfer and aging model) with ACY-738 as a single agent resulted in 1) overall survival advantage, 2) reduction of tumor burden, 3) reduction in PD-L1 expression in the malignant B cell population and 4) decreased circulating Treg numbers. Furthermore, we demonstrated that in an in vitrostudy, treatment of HDAC6i with ibrutinib in CLL cell lines render strong synergistic cell killing. In our current study of this combinatorial approach, using the adoptive transfer euTCL1 model receiving Ibrutinib in drinking water and ACY-738 in feed, we demonstrate a further decrease in tumor burden when compared to single agent treatment with either compound alone. This observed effect on tumor burden occurred in conjunction with decreases in co-inhibitory molecules and circulating Treg frequency. The combination was well tolerated and no significant toxicity was observed. Since aberrant over-expression of HDAC6 in CLL cell lines and patient's samples have already been demonstrated (Van Damme et al 2012, Sahakian et al 2012) we sought to understand its mechanistic role in BCR survival pathways of CLL. Our studiesin normal B cells isolated from C57BL/6 and HDAC6KO mice, demonstrated a reduction in phosphorylation of BTK, ERK, and AKT. Similar results were observed when we compared euTCL1 to euTCL1/HDAC6KO B cells. Additionally,we observed decreased phosphorylation of ERK and SYK in MEC2-HDAC6KD cells when compared to parental control CLL cells. Moreover, RNA-Seq studies of the eu-TCL1/HDAC6KO versus euTCL1 B cells showed several key BCR signaling proteins altered by the deletion of HDAC6. In conclusion, these results from our preclinical CLL models suggest that combinatorial therapy of Ibrutinib plus HDAC6i show synergistic inhibition of BCR signaling and therefore a better overall treatment outcome. Disclosures Quayle: Acetylon Pharmaceuticals: Employment, Equity Ownership. Jones:Acetylon Pharmaceuticals, Inc.: Employment, Equity Ownership. Pinilla-Ibarz:Gilead: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Novartis: Consultancy; Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Speakers Bureau.

Prognostic importance of primary tumor resection and synchronous metastasis on overall survival in metastatic colorectal cancer: Data from the FIRE-3 (AIO KRK-0306) study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4070-4070
Author(s):  
Jobst C. von Einem ◽  
Sebastian Stintzing ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
Alexander Kiani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Primary Tumor Resection ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
The Impact ◽  
First Line Treatment

4070 Background: The FIRE-3 study (AIO KRK-0306) was designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. Overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Methods: In the present analysis of the FIRE-3 trial we explored the impact of primary tumor resection on outcome in relation to anti-EGFR vs. anti-VEGF treatment. Furthermore, we investigated the prognostic value of synchronous versus metachronous metastases. Results: In patients with synchronous disease no significant difference in OS was detected when comparing resected (n=339) vs. non-resected (n=97) patients (p-value: 0.29, HR: 1.17, 95%-CI: 0.88 – 1.55). In the cetuximab arm, resection (n=167) showed no significant benefit in OS when compared to non-resection (n=52) (p-value: 0.51, HR: 1.15, 95%-CI: 0.77 – 1.71). Treated with bevacizumab, similar results were present, when comparing resection (n=172) vs. non-resection (n=45); (p-value: 0.29, HR: 1.25, 95%-CI: 0.83 – 1.9). A strong trend was seen when comparing OS in treatment arms cet. (n=219) vs. bev. (n=217)) for patients with synchronous disease; (p-value: 0.05, HR: 1,26, 95%-CI: 1.0 - 1.59). 436/592 pts suffered from synchronous, 153/592 from metachronous disease (in 3/592 pts the information was not given). Median OS in pts with synchronous disease was 24.5 months and 29.5 in pts with metachronous disease (p-value: 0.02, HR: 0.76, 95%-CI: 0.6 - 0.96). In pts treated in the cetuximab arm metachronous disease (n=77) was associated with a trend towards longer OS when compared to synchronous disease (n= 219) (p-value: 0.13, HR: 0.76, 95%-CI: 0.54 – 1.1). The same effect was present in the bevacizumab arm (p-value: 0.05, HR: 0.73, 95%-CI 0.53 – 1.0) when comparing pts with synchronous disease (n=217) vs. pts. with metachronous disease (n=76). Conclusions: In the FIRE-3 study, metachronous disease was associated with superior OS compared to synchronous disease. This finding was accentuated in the bevacizumab arm. The role of resection of the primary tumor had no impact on survival. Clinical trial information: NCT00433927 .

scholarly journals CPX-351 Enables Administration of Consolidation Treatment in the Outpatient Setting and Increases the Time Spent out of the Hospital after Completion of AML Treatment Compared with 7+3

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4507-4507 ◽  
Author(s):  
Jeffrey E Lancet ◽  
Phillip Cyr ◽  
Naomi Sacks ◽  
Michael T. Chiarella ◽  
Arthur C. Louie ◽  
...  
Keyword(s):  
Research Funding ◽  
Hospital Admissions ◽  
Statistical Significance ◽  
Outpatient Setting ◽  
Employment Equity ◽  
Specific Patient ◽  
Secondary Aml ◽  
Significant Difference ◽  
Equity Ownership ◽  
The Impact

Abstract Introduction: CPX-351 is a liposomal formulation of a synergistic 5:1 molar ratio of cytarabine and daunorubicin for the treatment for Acute Myeloid Leukemia (AML). CPX-351 possesses important pharmacologic differences that favorably impact efficacy and safety and may confer certain benefits related to health care resource use (HRU). CPX-351 has been granted fast track approval by the FDA, based on Phase 2 clinical trial (Study 204) results (Lancet, et al., Blood. 2014;123(21):3239-3246). Study 204 was analyzed to develop directional data regarding the impact of CPX-351 on HRU in relation to its clinical benefit. Materials and Methods: Baseline characteristics from Study 204 were checked to confirm balanced patient demographics and AML risk factors. Study treatment (CPX-351 vs. 7+3), and its administration (number of inductions and consolidations) and setting (inpatient vs. outpatient) were viewed in the context of patient outcomes (response, 60-day mortality, and transplant). Time spent within and outside the hospital, free of an event (starting from randomization until documentation of persistent disease, start of transplant, relapse, or death, whichever occurred first) were calculated and compared by treatment arm. An intent-to-treat (ITT) analysis was performed so that the experience for 10 patients who crossover to CPX-351 were attributed to 7+3. Statistical significance was assessed using a one-tailed t-test. All results are unadjusted for potential confounders and the study was not powered to showed statistical significant difference of HRU. Results: 85 patients were randomized to CPX-351 and 41 to the 7+3 control arm. The two study arms were balanced for age, sex, race, AML type (de novo vs. secondary AML), performance status, and cytogenetic risk. The prospectively defined survival analysis of the secondary AML subgroup showed significant improvement in the CPX-351 arm (HR=0.51, p=0.04). 60-day mortality was also markedly improved following CPX-351 (4.7% vs. 14.6%). CPX-351 patients were more likely to have only one induction (80% vs. 70.7%; p = 0.13) and more likely to respond to induction (66.7% vs. 51.2%; p = 0.07). Among responders, CPX-351 patients were more likely to achieve remission with one induction only (82.1% vs. 72.4%; p = 0.15). A total of 52 patients who responded to induction went on to receive consolidation (CPX-351: n=37; 7+3: n=15). A much larger proportion of responding CPX-351 patients received consolidation in the outpatient setting (40.5% vs. 13.3%; p = 0.02), and had only one induction (86.5%; vs. 66.7%). Nearly all CPX-351 transplanted patients were responders compared with control (13CR/14 (92.9%) vs. 5CR/7 (71.4%); p =0.1). The number of hospital admissions and total days spent in hospital are key contributors to HRU. CPX-351 patients had fewer hospital admissions per patient compared to 7+3 (mean 1.51 vs. 1.76, p < 0.05). CPX-351 induction in all patients was associated with more days in hospital (median 35 vs. 28 days) than 7+3. However, among responding patients total days in hospital for induction plus consolidation was similar (median 42 vs. 43 days) with fewer days of hospitalization required for consolidation in the CPX-351 arm (median 4 vs. 11 days). Although CPX-351 was associated with longer hospitalization for induction among all patients it was also associated with greater time spent outside of the hospital after completion of AML treatment (median: 129 vs. 76 days). Discussion: CPX-351 is associated with better clinical outcomes, including, lower early death rates, higher response rates, and improved overall survival in specific patient subsets. This report provides the first evidence that number of hospitalizations per patient, a key driver of hospital costs, is significantly less for CPX-351 and that overall days in hospital is similar for CPX-351 and 7+3 among responding patients, with many CPX-351 patients receiving consolidation as outpatients. In addition, CPX-351 improves the duration and proportion of time spent as an outpatient following completion of AML treatment. A more robust analysis of HRU is planned for the Phase 3 trial. Disclosures Lancet: Seattle Genetics: Consultancy; Kalo-Bios: Consultancy; Amgen: Consultancy; Celgene: Consultancy, Research Funding; Pfizer: Consultancy; Boehringer-Ingelheim: Consultancy. Cyr:Celator Pharmaceuticals: Consultancy. Chiarella:Celator Pharmaceuticals: Employment, Equity Ownership. Louie:Celator Pharmaceuticals, Inc.: Employment, Equity Ownership. Cortes:Teva: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; BerGenBio AS: Research Funding; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

scholarly journals Comparison of Two Different Vinblastine Dosages for Treatment of Cutaneous Mast Cell Tumor in Dogs

2020 ◽  
Vol 48 ◽  
Author(s):  
Lucas Cavalli Kluthcovsky ◽  
Bruna Fernanda Firmo ◽  
Pedro Carvalho Cassino ◽  
Andrigo Barboza De Nardi ◽  
Jorge Luiz Costa Castro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mast Cell ◽  
Survival Time ◽  
Dose Intensity ◽  
Control Group ◽  
Histopathological Diagnosis ◽  
Clinical Variables ◽  
Overall Survival Time ◽  
Significant Difference ◽  
The Impact

Background: Mast cell tumors (MCT) are among the most common malignant cutaneous neoplasm in dogs with variable biologic behavior and remain a therapeutic challenge in high-grade cases. Surgery remains the primary treatment for canine MCT; however, chemotherapy and radiation therapy are commonly used to treat aggressive cases. The combination of vinblastine (VBL) at a dose of 2 mg/m² and prednisone is the classically described protocol for MCT treatment. Studies have shown the safety of higher VBL doses for dogs with MCT, but there is a lack of information regarding dose intensity and outcome as a goal after chemotherapy.   This study aimed to evaluate the impact of a higher dose of VBL on MCT treatment outcome.Materials, Methods & Results: This was an observational and comparative study conducted in two different Veterinary Teaching Hospitals. Client-owned dogs with histopathological diagnosis of grade II or III MCT were selected and underwent at least four chemotherapy sessions with VBL and prednisone. The experimental group (EG) consisted of 18 dogs that received a dose of 3 mg/m² VBL treated in one institution. The control group (CG) included 31 dogs that received a dose of 2 mg/m² VBL treated at the other institution. All dogs treated in both groups had a clinical and complete blood count (CBC) evaluation performed previous the start of chemotherapy (T0) and before each weekly treatment (T1, T2, T3, and T4). After treatment, dogs in both groups were followed-up for the recurrence rate and overall survival time after diagnosis. There was no significant difference in clinical variables between EG and CG. During treatment, dogs of EG showed a significant reduction in erythrocyte, hemoglobin, and hematocrit values between T0 and T1, T2, T3, and T4 (P < 0.001). Comparatively, the CG showed significant reduction in hemoglobin (P = 0.02) and total leucocytes (P = 0.001) values in the same period. Despite these findings, these hematological parameters did not exceed the lower limit for the species in both groups. There was a higher-grade neutropenia one week after the first VBL application (T2) in both groups, with no statistical difference in neutrophil counts at T2 or during the whole treatment. There were discrete and self-limited episodes of anorexia, vomiting, and diarrhea in both groups. After chemotherapy, dogs in EG showed a significantly lower rate of recurrence than dogs in CG (P = 0.02). There was no significant difference in the overall survival time between groups.Discussion: The absence of significant differences in clinical variables (e.g. sex, age, histological grading, and tumor location) between EG and CG suggests that the groups may be similar regarding these parameters. All dogs included in this study had a recommendation for MCT post-operative chemotherapy treatment. VBL action is non-selective and anemia is not a commonly described adverse effect associated with its administration. Despite that, EG dogs exhibited a reduction in erythrocytes, hematocrit, and hemoglobin, and CG dogs in hemoglobin throughout T0 to T4. The highest number of neutropenia episodes occurred during T2, after the first VBL application in both groups with a trend of stabilization after T2, which is compatible with findings described in the literature. Any dog of EG or CG had to interrupt the treatment due to hematological or gastrointestinal toxicity or died during treatment. The role of VBL dose intensity in outcome is still debatable for dogs with MCT, once it is a multifactorial disease with variable presentation. In this study, there was no difference in overall survival time after diagnosis between groups, and EG dogs treated with a higher VBL dose showed significantly less tumor recurrence than CG.

Effect of New Institutional Algorithm for Chemotherapy Induced Anemia (CIA) on Erythropoiesis-Stimulating Agent Treatment Patterns and Costs in Lymphoma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1299-1299
Author(s):  
Aditya D. Raju ◽  
Lal S. Lal ◽  
Lesley-Ann Miller ◽  
Hua Chen ◽  
Sujit S Sansgiry
Keyword(s):  
Treatment Patterns ◽  
Cancer Center ◽  
Control Group ◽  
Chi Square ◽  
University Of Texas ◽  
Institutional Practice ◽  
Significant Difference ◽  
Study Population ◽  
The Mean ◽  
The Impact

Abstract Recently there has been accumulating data regarding the increased risks of mortality, thrombosis, cardiovascular events, and of possible tumor promotion when administering erythropoiesis-stimulating agents (ESAs) to a target hemoglobin (Hgb) level of 12 g/dL. In response to this evidence, the FDA mandated a Black Box warning and the CMS mandated changes in coverage for ESAs. Subsequently, in December, 2007, the University of Texas M.D. Anderson Cancer Center (M. D. Anderson) developed and implemented an institutional practice algorithm to advise physicians regarding treatment of CIA, which included recommendations for the initiation and continued use of ESAs. The objective of this study was to assess the impact of the new institutional practice algorithm on the treatment patterns and costs of CIA in lymphoma patients. The study design was a retrospective study with a historical control group. The historical controls (pre-group) consisted of lymphoma patients diagnosed with CIA between January 1, 2007–April 30, 2007 and the cases (post-group) consisted of lymphoma patients diagnosed with CIA between January 1, 2008–April 30, 2008, who were all followed for a period of up to 16 weeks. Patient demographics, chemotherapy type, ESA type and dosage, transfusions received, Hgb values at the time of ESA usage and transfusions (for all doses and transfusions received at the institution during the study period), and costs for ESA treatment and transfusions were extracted from patient medical charts and institutional databases at M. D. Anderson. Descriptive statistics, t-tests, Mann- Whitney U, and chi-square analyses were conducted to evaluate the study objectives. The study population consisted of 154 patients; 90 patients in the pre-group and 64 patients in the post-group. Both groups had similar demographic and baseline clinical characteristics. In the post period, though there was a significant decrease in the overall amount of ESA units dispensed per patient (p=0.0125), there was an increase in the amount of ESA units dispensed in the first eight weeks of treatment (p=0.03), indicating potentially less use of outside pharmacies. There was a significant decrease in the mean Hgb at the time of ESA usage, from 9.59g/dL to 8.98g/dL (p&lt;0.0001). The proportion of patients who received an ESA at a Hgb level &gt; 10 g/dL decreased significantly, from 66% to 17% (p&lt;0.0001). There was no significant difference in the mean Hgb level at week 4 of therapy, which may indicate that patients were not clinically affected by the change in practice. There was also no significant difference in the number of transfusions administered, or the costs associated with the treatment of CIA in the study population. The results indicate that the new institutional algorithm was effective in altering the treatment patterns of CIA with respect to the ESA units prescribed and dispensed and the hemoglobin levels at the time of ESA usage in lymphoma patients.

Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
Tetsuya Mitsudomi ◽  
Satoshi Morita ◽  
Yasushi Yatabe ◽  
Shunichi Negoro ◽  
Isamu Okamoto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
The Impact ◽  
Egfr Tki ◽  
First Line Treatment ◽  
Platinum Doublet

7521 Background: WJTOG3405 met its primary endpoint of progression free survival (PFS) (9.2 months (mo.) for G vs. 6.3 mo. for CD, hazard ratio (HR) 0.489, 95% confidence interval (CI): 0.336-0.710). (Mitsudomi et al., Lancet Oncol., 2010). However, the impact on overall survival (OS) was not clear then because of relatively short follow-up period. Methods: Overall survival (OS) was re-evaluated using updated data (data cutoff, 31 July, 2011, median follow-up, 34 months) for 172 patients. Results: Eighty-two events had occurred (48%). Median survival time (MST) for G arm was 36 mo. (95% CI: 26.3 -) which was not significantly different from 39 mo. (95% CI: 31.2 -) for CD arm (HR 1.185, 95% CI 0.767-1.829). Multivariate analysis using Cox proportional hazards model revealed that none of covariates (treatment arm, smoking status, sex, age, postoperative recurrence or IIIB/IV, and mutation type) significantly affected OS. In the G arm, MST of patients with exon 19 deletion (36 mo.) was comparable to that of patients with L858R (35 mo.). In the CD arm, 78 patients (91%) received EGFR-TKI as the 2nd or later line treatment, whereas in the G arm, 52 patients (61%) received platinum doublet. Accordingly, 130 patients received both platinum doublet and EGFR-tyrosine kinase inhibitor (TKI) and 34 patients received EGFR-TKI without platinum doublet in their whole courses of therapy. MST for the former and the latter group were 36 months (95% CI: 31.2-45.7) and 45 months (95% CI: 25.6-), without significant difference. Conclusions: This update OS analysis revealed that G for advanced NSCLC with EGFR mutation offers distinct survival benefit of 3 years. There was no difference in OS whether the first-line treatment was G or CD, in accordance with the precedent studies. The reason why PFS difference was not translated into OS difference is probably due to high cross over rate to EGFR-TKI. However, it was noteworthy that 40% of patients in the G arm could be managed without platinum doublet and yet had similar outcome.

Real life data from Turkey regarding the impact of first-line sunitinib and pazopanib in metastatic renal cell cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16075-e16075 ◽  
Author(s):  
Ulas Isik ◽  
Osman Kostek ◽  
Gokcen Demiray ◽  
Ahmet Dirican ◽  
Melih Simsek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Cell ◽  
The Other ◽  
Line Treatment ◽  
First Line ◽  
Treatment Approaches ◽  
Common Cancer ◽  
Significant Difference ◽  
The Impact ◽  
First Line Treatment

e16075 Background: Although the distribution in the world varies widely, renal cell carcinoma (RCC) is the ninth most common cancer, especially in males. It’s the seventh most common cancer in Turkey. In this study, the progression-free survival (PFS) and overall survival (OS) of patients with metastatic RCC (mRCC) who were treated at 13 centers in our country were evaluated and the efficacy of first-line treatment approaches was compared. Methods: Data of mRCC patients admitted to 13 outpatient clinics in Turkey between 2008 and 2018 were reviewed retrospectively. Demographic characteristics, pre-treatment clinical evaluations, information about treatment approaches and survival outcomes of the patients were collected. All medical records were collected by a detailed review of the patients’ charts. The median and percentage values were frequently signified for defining of central trends. Kaplan-Meier method was applied for OS analyzes and log-rank test with Cox-regression models were applied for the evaluation of prognostic factors. Results: Data from files of 262 patients were reviewed. Twelve of these patients were excluded from the study because they could not receive treatment due to comorbidities and other reasons at metastatic stage of the disease. Of the patients, 100 (40%) were female and 150 (60%) were male. Median age was 60 (range 21-83). For the entire group, the median PFS (mPFS) was 27.6 months and the median overall survival (mOS) was 46.1 months. In terms of first-line treatment of metastatic disease, 41.3% of the patients received sunitinib, 48.8% of the patients received pazopanib, 15.8% of the patients received other treatments. PFS of the patients receiving sunitinib, pazopanib and the other treatments were 26.3 months, 34.2 months and 14.2 months, respectively. There was no statistically significant difference between PFS of the patients receiving sunitinib and pazopanib (p = 0.05). mOS was 54 months in sunitinib arm, 54.9 months in pazopanib arm and 23.3 months in the other treatment arm. There was no statistically significant difference between two treatment agents in terms of mOS (p = 0.43). Conclusions: Pazopanib was more commonly prescribed in Turkey. There were no statistically significant differences between mPFS and mOS of the patients who received sunitinib and pazopanib for the first-line treatment of mRCC. With increased use of immunotherapeutic agents for the first-line treatment of mRCC in our country, improvement in mOS could be expected.

Analysis of the Impact and Burden of Illness of Myelofibrosis in the US

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 972-972
Author(s):  
Hongwei Wang ◽  
Jyotsna Mehta ◽  
Usman Iqbal ◽  
Ruben A. Mesa
Keyword(s):  
Annual Cost ◽  
Research Funding ◽  
Burden Of Illness ◽  
National Database ◽  
Control Group ◽  
Employment Equity ◽  
Patient Demographics ◽  
The Us ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 972 Background: Myelofibrosis (MF) is a Philadelphia chromosome–negative myeloproliferative neoplasm. Common disease manifestations include bone marrow failure, enlarged spleen due to extramedulary hematopoiesis (splenomegaly), debilitating symptoms including fatigue, night sweats, pruritus, early satiety, abdominal pain and discomfort, and marked decrement in patient's quality of life (QoL). Decreased survival is a hallmark of the disease as a result of infections, bleeding and leukemic transformations. There are no recent literature estimates looking at clinical and economic burden of illness of this rare disease. The objective of this study was to describe patient demographics, prevalence, comorbidities, utilization and costs for MF using real-world data. Methods: The US IMPACT® insurance claims database was used to retrospectively identify unique patients with any MF (including all primary and secondary MF cases) between 1/1/08 and 12/31/10. The IMPACT database is a fully de-identified, HIPAA compliant national database that captures the complete medical history for over 100 million managed-care individuals, including patient demographics, disease description, laboratory results, details of medical, pharmacy, outpatient, and inpatient claims. These databases can track patients longitudinally over multiple years, are linked at the patient level by a unique identifier that is consistent across services, health plans, and time and are representative of the US population. ICD-9-CM codes were used to identify MF. The Charlson Comorbidity Index (CCI) was employed to assess overall comorbid disease status. Enrollment was restricted to those with full year of medical and pharmacy benefit. Control group was age and gender matched but without any diagnosis of myelofibrosis. Medical costs include inpatient, outpatient and emergency room cost. Results: In 2010, 433 patients with MF (mean age 60, 50% female) were identified from about 12 million enrollees. This corresponds to an age-adjusted prevalence of 5.4 per 100,000 patients. Compared with age-gender matched control patients, MF patients had higher overall comorbidities (mean CCI of 2.1 vs. 0.9), were hospitalized more often (34% vs. 11%), had higher number of average hospital days (7 vs. 1 day), and had more outpatient office visits (58 vs. 22) in 2010. Accordingly, MF patients incurred much higher average annual cost ($54,168 vs $10,203) driven by both medical ($45,646 vs $7,987) and pharmacy ($8,523 vs $2,216) cost. Over a period of 3 years, annual cost of MF ranged from $54,000-$68,000. The utilization rate and total cost in each of conditions were significantly higher than those of their matched patients in each of the three years. Conclusions: Myelofibrosis is associated with a significant burden of illness. Patient with MF incurred about five times healthcare expenditure than those in the control group. Our study indicates that MF-associated medical resource utilization and the corresponding expenditures for those services are substantive. Continued efforts in the development of more efficacious treatments for myelofibrosis are needed in order to reduce the burden of illness associated with this disease. Disclosures: Wang: Sanofi: Employment, Equity Ownership. Mehta:Sanofi: Employment. Iqbal:Sanofi: Employment, Equity Ownership. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

scholarly journals Molecular Classification of AML-MRC Reveals a Distinct Profile and Identifies MRC-like Patients with Poor Overall Survival

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2735-2735 ◽  
Author(s):  
Constance Baer ◽  
Wencke Walter ◽  
Anna Stengel ◽  
Stephan Hutter ◽  
Manja Meggendorfer ◽  
...  
Keyword(s):  
Machine Learning ◽  
Overall Survival ◽  
Genetic Model ◽  
Fusion Gene ◽  
Molecular Profile ◽  
Point System ◽  
Employment Equity ◽  
Cytogenetic Abnormalities ◽  
Equity Ownership ◽  
The Impact

Background: AML with myelodysplasia related changes (AML-MRC) is as specific WHO category with poor prognosis. It requires ≥ 20% of blasts, and (1) the history of MDS or MDS/MPN, or (2) "MDS related cytogenetic abnormalities", or (3) multilineage dysplasia. Drugs such as Vyxeos® have been approved by FDA and EMA only for treatment of t-AML or AML-MRC. However, counting blasts or grading dysplasia in clinical routine is hampered by limited reproducibility due to different levels of expertise and small phenotypic alterations, challenging upfront treatment decisions. Cytogenetics is not available in all cases and has 5-10 days of turnaround time (TAT). In contrast, next-generation sequencing (NGS) panels for AML are now broadly available at faster TAT. Aim: (1) Use machine learning to define a molecular AML-MRC signature; (2) compare the impact of conventional WHO definitions and molecular factors on classification and outcome. Patients and Methods: Gold standard routine AML diagnosis was performed on 739 cases. Overall survival (OS) data was available for 619 patients. Amplification-free whole genome sequencing was performed on HiSeqX and NovaSeq with median coverage of 106x. Gender-matched reference DNA was used for unmatched normal variant calling with Strelka2. Pindel was used for FLT3-ITD. For variant classification, we applied a GnomAD cutoff of 0.0005 and filtered on protein-truncating and (likely) pathogenic variants from databases. Results: According to WHO standards 165/739 (22%) cases fulfilled MRC criteria (96 male; 69 female). The non-MRC cohort (n=574) represents a heterogeneous AML population incl. the WHO defined recurrent cytogenetic abnormalities or t-AML (301 male, 273 female). Median age was higher in the MRC cohort (73 [22-90] vs. 64 [18- 93] years, p<.001) and OS was significantly shorter (median 6 vs. 23 months, p<.001). Mutation analysis was limited to 73 frequently mutated genes, in order to allow application of our model on prospective diagnostic cases analyzed by common routine panels. In the MRC group, up to seven mutations were found per patient and an average of 2.7 genes per patient were mutated. The most frequently mutated gene in AML-MRC was TP53 (62/165, 38%) as expected by the inclusion of complex karyotypes. TP53 mutations were associated with shorter OS in the MRC cohort (median: 3 vs. 11 months, p =.001). We used machine learning (ML) approaches to identify with LASSO regression and 10-fold cross-validation the most informative features to distinguish between MRC and patients without MRC. The dataset was randomly divided into a training (90%) and test set (10%) and the procedure was repeated 500 times to cover all the variance in the dataset and to extract the most reliable factors. Factors with the highest weight on AML-MRC prediction were mutations in TP53, RUNX1, SETBP1, splicing factors and epigenetic regulators, and absence of mutations in NPM1, CEBPA and others (s. figure). In order to allow our model to be used in a routine diagnostic workflow, we also used the genes identified by ML but classified mutations by a simpler point system (≥2 points as cutoff for MRC, s. figure). This allowed us to identify 83% (137/165 by ML) and 70% (116/165 by points) of cases currently defined as MRC solely by molecular genetics. Including cytogenetic data and patient's history in an informed genetic model results in 99% (164/165 by ML) and 96% (159/165 by points) of true positive MRC definition. However, the molecular models classified 112 (ML) and 80 (points) of the 574 non-MRC cases, as being AML-MRC. Even after excluding AML with recurrent cytogenetic abnormalities and t-AML, 14% (82/574 DL) or 11% (63/574 points) show a MRC-like molecular profile. In both models MRC-like patients had dismal outcome analogous to AML-MRC (median OS: 6 months for both) and significantly inferior to remaining non-MRC patients (6 vs. 35 months, s. figure). Conclusions: (1) Using patients' history and genetic information instead of morphology allow to identify 96-99% of AML-MRC as defined in WHO today. In the future, extended NGS panels (e.g. incl. fusion gene detection) will allow fast and standardized AML-MRC classification even without chromosome banding analysis. (2) The molecular MRC-like pattern can be found in >10% of patients currently not classified as AML-MRC but with comparably poor OS. This suggests considering MRC treatment strategies for patients with MRC-like molecular profile. Disclosures Baer: MLL Munich Leukemia Laboratory: Employment. Walter:MLL Munich Leukemia Laboratory: Employment. Stengel:MLL Munich Leukemia Laboratory: Employment. Hutter:MLL Munich Leukemia Laboratory: Employment. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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