Efficacy, Tolerability and Cost Benefit of a 5-Day Azacitidine Regimen

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5034-5034
Author(s):  
Francesca Pierdomenico ◽  
Antonio Almeida
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Total Dose ◽  
Haematological Toxicity ◽  
Cost Effective ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 5034 Background: Azacitidine is a hypomethylating agent indicated for treatment of higher risk Myelodysplastic Syndromes (MDS). A recently published phase III trial demonstrated improved overall survival (OS) of MDS patients treated with Azacitidine compared to those receiving conventional care regimens, thus establishing this treatment option as first line therapy in those patients for whom bone marrow transplantation is not an option. Standard regime has been 75 mg /m2/day during 7 days; however several other treatment schedules have been explored that may have equal efficacy and tolerability though being more cost-effective. Aims: Evaluate the efficacy of Azacitidine regimen in terms of transfusion independence (TI), overall response (OR), AML transformation and tolerability in patients with higher risk MDS and AML with dysplasia. Methods: Higher risk (IPSS INT-2 and high risk) MDS patients were treated at a single institution with Azacitidine with a dosing regime of 500 mg/m2 every 4 weeks administered over 5 days. The total dose was adjusted so that entire vials were used. OR, including complete response (CR), haematological response (HR) and partial response (PR) and TI, defined according to the 2000 International Working Group Criteria (IWG), were assessed by blood and bone marrow examination. Treatment cycles were repeated until toxicity or disease progression. Results: A total of 38 patients were treated with Azacitidine between January 2007 and December 2010. Mean age was 68 years old (range 85–33) and male sex was predominant (M:F of 1.5) Fifteen patients had refractory anaemia with excess blasts, eleven had AML with dysplasia, five had chronic myelomonocytic leukaemia, tree had refractory cytopenias with multilineage dysplasia and four had acute erythroblastic leukemia. Most patients were high risk according to IPSS scoring (82%). Azacytidine was used as first line therapy in 32% and as second line in 61%. An average of 5 cycles (1–22) per patient were administered. The TI rate was of 45%, with average response duration of 6.5 months. OR rate was of 32% (9 CR, 1 HR and 2 PR). Twenty-two patients died during the follow-up period. Six patients progressed to AML: five of them had never shown any response to Azacitidine, while the other one had obtained TI. Median survival from diagnosis was of 22 months, while median survival from beginning of treatment was of 12 months. Tolerability was good, mainly grades I and II gastrointestinal and skin toxicity. Eleven patients (26%) had Grade III haematological toxicity and four (11%) suffered Grade IV haematological toxicity. The Azacitidine schedule using 500 mg/m2/4 weeks with the total dose adjusted across the 5 days in order to avoid wastage, instead of 75 mg/m2/day during 7 days, allowed for significant costs reductions. Conclusion: The efficacy of Azacitidine in achieving TI and prolonging survival in MDS is well recognized. In this study, Azacitidine improved quality of life and overall survival regardless of the quality of response. Treatment was well tolerated, with limited toxicity. Our results, though coming from a small group of patients, were comparable to what reported in the literature in terms of efficacy and tolerability, and we showed that it is cost effective to use our schedule regime. Disclosures: Almeida: Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau.

scholarly journals Differential Response to Hypomethylating Agents Based on Sex: A Report on Behalf of the MDS Clinical Research Consortium (MDS CRC)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2889-2889
Author(s):  
Amy E. DeZern ◽  
Amer M. Zeidan ◽  
John Barnard ◽  
Wesley Hand ◽  
Najla Al Ali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
P Value ◽  
Continuous Variables ◽  
Hypomethylating Agents ◽  
First Line ◽  
Bone Marrow Blast ◽  
First Line Therapy ◽  
Line Therapy ◽  
Time Of Presentation

Abstract Background The standard first-line therapy for higher-risk myelodysplastic syndromes (MDS) are the hypomethylating agents (HMA). While clinical characteristics, molecular markers, and karyotype can contribute to predicting prognosis in MDS, these parameters have not identified differential response rates between the HMAs decitabine (DAC) and azacitidine (AZA). Gender differences have been associated with varied outcomes in multiple cancers, and are thought to be related to differences in disease biology, treatment response, or adherence to therapy. Relevant to MDS, gender can effect expression of cytidine deaminase, which inactivates the HMAs. Male have increased levels compared to females. The impact of gender on response to HMAs is not established. Methods A dataset from the MDS CRC database was analyzed. Patients (pts) were diagnosed with higher-risk MDS (International Prognostic Scoring System (IPSS) Int-2 or High) and per 2008 WHO criteria and were treated with AZA or DAC as first-line therapy. Response was assessed per International Working Group (IWG) criteria (2006). The IPSS and its revision (IPSS-R) were calculated at presentation. Missing data were multiply imputed 100 times using the mice approach. Differences among variables were evaluated by the chi-square test and Mann-Whitney U test for categorical and continuous variables, respectively, with continuous variables summarized by median and range. Overall survival (OS) was calculated from presentation date to date of death or last follow up. Propensity scores were calculated for DAC vs AZA using all variables available pre-treatment. Propensity weighted Cox proportional analysis and log-rank tests were used to model and test OS. Results Of 625 higher-risk MDS pts, 33.7% were women (Table 1). The median OS for the cohort was 16.9 months (95% CI 15.6-18.2); 17.8 months for men (95% CI 16.4-19.2) and 15.0 months for women (95% CI 12.1-18.6). Approximately one third of pts received DAC as front line HMA in both gender groups. While most variables had similar distributions between DAC and AZA within genders, two variables showed differences between HMA treatments in both genders: bone marrow blast percentage at diagnosis and IPSS-R cytogenetic category, with blast percentage consistently higher in the DAC treated set. In addition, DAC-treated females were on treatment longer than AZA-treated females There was no difference in median OS across gender (p=0.33). DAC-treated pts had marginally better OS than AZA pts (p=0.043), (median OS of 18.7 months vs 16.3 months), but the difference varied strongly by gender (Figure 1). Female DAC pts had much better OS than female AZA pts (p=0.0014), with a median OS of 21.2 months (95% CI 16.1-27.9) versus 13.1 months (95% CI 10.7-15.9). Males showed no significant difference (p=0.59), with a median OS of 18.3 months (95% CI 14.9-22.2) compared to 17.6 years (95% CI 16.0-19.5). Female DAC survival improvement remained significant in a Cox PH analysis after adjusting for cytogenetic category and bone marrow blast % at diagnosis. (Figure 1) Conclusion Women with higher-risk MDS may live longer when treated with DAC than with AZA. While factoring in gender as a variable in therapeutic choice between the HMAs remains premature, future prospective investigations of both drugs in men and women are warranted. Table 1. Patient characteristics by Sex FemaleN=210, 33.7% MaleN=415, 66.3% Parameter DAC AZA P-value DAC AZA P-value N=7234.3% N=138 65.7% N=130 31.3% N=285 68.7% Age, years 67.4 35-84 68.9 36-91 0.222 70.0 38-89 70.8 31-99 0.641 ANC X 109 L 1.06 0.04-27.7 0.83 0.10-20.4 0.085 1.04 0.02-44.9 1.01 0.01-42.6 0.900 Platelets X 109 L 57.8 2.0-412.4 59.4 4.9-655.2 0.820 55.6 3.0-654 66.2 2.5-451.3 0.095 Hemoglobin g/dL 9.53 4.38-12.90 9.27 4.91-14.04 0.271 9.40 4.10-13.93 9.13 3.00-15.91 0.086 Bone marrow blasts % 13.0 0.27-29 10.0 0-84 <0.001 13.1 0-29.1 9.9 0-83 <0.001 Time on HMA (months) 6.0 0.16-30.1 4.2 0.14-41.3 0.055 4.7 0.10-38.8 5.4 0.03-55.0 0.840 IPSS-R CategoryLow/Very LowIntermediateHighVery High 0.3 12.5 36.9 50.4 0.1 10.2 29.5 60.2 0.496 0.1 11.8 33.6 54.5 1.8 9.5 35.3 53.3 0.567 IPSS-R Cytogenetic CatVery PoorPoorIntermediateGood/Very Good 47.3 3.2 21.1 29.7 43.1 21.6 16.9 18.8 0.0011 42.4 8.1 18.5 31.0 42.4 11.7 25.3 20.6 0.086 Progression to AML (Y) 46.5 47.4 0.936 44.8 43.1 0.803 Figure 1. Overall survival by HMA and Sex (and breakdown by HMA) from Time of Presentation to CRC Institution Figure 1. Overall survival by HMA and Sex (and breakdown by HMA) from Time of Presentation to CRC Institution Disclosures Komrokji: Incyte: Consultancy; Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau; Celgene: Consultancy, Research Funding. Steensma:Celgene: Consultancy; Amgen: Consultancy; Incyte: Consultancy; Onconova: Consultancy. Sekeres:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

Diffuse Pattern of Bone Marrow Involvement in MRI Is Associated with High Risk Cytogenetics and Poor Outcome in Newly Diagnosed, Symptomatic Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3920-3920
Author(s):  
Lia A Moulopoulos ◽  
Efstathios Kastritis ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Maria Roussou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Newly Diagnosed ◽  
Poor Survival ◽  
Normal Pattern ◽  
First Line ◽  
Agent Based ◽  
First Line Therapy ◽  
Line Therapy ◽  
Novel Agent

Abstract Abstract 3920 Magnetic Resonance Imaging (MRI) and specific recurrent cytogenetic abnormalities offer important prognostic information for multiple myeloma (MM) patients. However, limited data are available about the association between cytogenetic abnormalities and MRI patterns of marrow infiltration. To address this issue, we analyzed 203 newly-diagnosed, symptomatic patients who were treated in a single center, in Athens (Greece). The pattern of marrow involvement in MRI was recognized as: (1) normal when there was no evidence of abnormal signal; (2) focal which consisted of localized areas of abnormal marrow; (3) diffuse, in which the normal bone marrow is completely replaced; and (4) variegated which consists of innumerable small foci of disease on a background of intact marrow. Cytogenetic studies by FISH were performed in CD138 selected plasma cells using standard methodology. Eighty-six (42%) patients had focal pattern, 79 (39%) diffuse, 28 (14%) normal and 10 (5%) variegated pattern. Due to the low number of patients with variegated pattern and to our previous finding that variegated and diffuse patterns have similar outcomes, we analyzed these two patterns together. Patients with normal MRI pattern presented with better performance status (86% had ECOG PS ≤1 vs. 47% and 45% of patients with focal or diffuse patterns, p<0.001). Patients with focal or diffuse infiltration had features of advanced disease, such as anemia (Hb <10 g/dl; p<0.001), elevated serum LDH ≥300 IU/L (p=0.008) and advanced ISS stage (p<0.001). Patients with focal MRI pattern presented less often with renal impairment (eGFR <50 ml/min; p=0.017) but more often with lytic bone disease (p<0.001). The presence of del17p was more common in patients with diffuse pattern (22% vs. 10% in patients with focal and none in those with normal pattern, p=0.04). Similarly, add1q21 was more common in patients with diffuse pattern (37% vs. 13% and 15% for patients with focal or normal pattern; p=0.038). Del13q was observed also more frequent in diffuse pattern (48% vs. 28% and 24% for focal and normal pattern, p=0.056) while there were no significant differences in the frequency of t(4;14) and t(14;16) among patients with different MRI patterns. In general, 56% of patients with diffuse MRI pattern had high risk cytogenetics [any of del17p, add1q21, t(4;14) or t(14;16)] vs. 31% and 22% of patients with focal and normal patterns (p=0.012). Most patients (70%) received first line therapy based on novel agents (thalidomide, bortezomib or lenalidomide). Response to first line therapy was similar for patients with different MRI patterns (76%, 77.5% and 75% for focal, diffuse and normal pattern, respectively). However, patients who were treated upfront with conventional chemotherapy (CC) and had a diffuse MRI pattern had inferior response (46% vs. 79% and 83% for patients with focal and normal patterns, respectively, p=0.024). When patients were treated with novel agent-based frontline therapy, the response rates were similar among MRI patterns (89%, 74% and 73% for diffuse, focal and normal MRI patterns, respectively; p=NS). The median survival for patients with normal, focal and diffuse MRI patterns was 102, 57 and 37 months, respectively (p<0.001). The respective median survival for patients who were treated with CC was: not reached yet, 51 and 23.5 months (p<0.001) and in those who received novel agent-based regimens was 47 months for diffuse pattern vs. not reached for patients with focal or normal MRI pattern (p=0.05). When we adjusted for other clinical factors and for treatment type, then diffuse MRI pattern was independently associated with poor survival (HR: 3.018, p=0.024). Other factors that were independently associated with poor survival were age (>75 years; p<0.001), CC (p=0.001), ISS (p<0.001) and serum LDH ≥ 300 IU/L (p=0.05). When high risk cytogenetics were included in the multivariate model then only high risk cytogenetics (HR: 2, p=0.046), ISS stage (p=0.027) and serum LDH ≥300 IU/L were independently associated with poor survival. In conclusion, diffuse MRI pattern of bone marrow infiltration is associated with the presence of high risk cytogenetics, such as del17p and add1q21. The strong correlation of diffuse pattern with poor survival, even in the era of novel agents, suggests the need for more effective therapies for those patients and highlights the importance of the performance of baseline MRI in all patients with symptomatic disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Life Expectancy ◽  
Cost Effective ◽  
Base Case ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

scholarly journals Efficiency of lenalidomide, bortezomib and prednisone (RVP) in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 14 (1) ◽  
pp. 14-19 ◽  
Author(s):  
K. A. Belousov ◽  
T. A. Mitina ◽  
Yu. Yu. Chuksina ◽  
A. K. Golenkov ◽  
E. V. Kataeva ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Objective Response ◽  
Hematological Toxicity ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM). Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses. Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted. Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

Mo1310 OVER-THE-SCOPE CLIP AS FIRST-LINE THERAPY IN THE MANAGEMENT OF HIGH RISK BLEEDING PEPTIC-ULCERS: A CASE-MATCH CONTROL STUDY

2019 ◽  
Vol 89 (6) ◽  
pp. AB484
Author(s):  
Carlos Robles-Medranda ◽  
Juan M. Alcívar-Vásquez ◽  
Roberto Oleas ◽  
Jorge Baquerizo-Burgos ◽  
Juan I. Olmos ◽  
...  
Keyword(s):  
High Risk ◽  
Peptic Ulcers ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Bleeding Peptic Ulcers ◽  
Over The Scope Clip ◽  
Control Study
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