Economic analysis of decitabine versus best supportive care in the treatment of intermediate- and high-risk myelodysplastic syndromes (MDS).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 6600-6600
Author(s):  
E. Kim ◽  
F. Pan ◽  
S. Peng ◽  
R. Fleurence
Keyword(s):  
High Risk ◽  
Economic Analysis ◽  
Supportive Care ◽  
Myelodysplastic Syndromes ◽  
Best Supportive Care

A Retrospective Comparison of Matched Elderly Patients Treated with Laromustine (Cloretazine®) or Best Supportive Care or Low Dose Ara-C in the LRF AML14 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2960-2960 ◽  
Author(s):  
Robert Hills ◽  
Susan O’Brien ◽  
Verena Karsten ◽  
Alan K. Burnett ◽  
Francis Giles
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Low Dose ◽  
De Novo ◽  
Performance Status ◽  
Single Agent ◽  
Best Supportive Care ◽  
Cell Counts ◽  
Retrospective Comparison ◽  
De Novo Aml

Abstract Background : A substantial proportion of older patients with AML are considered unlikely to benefit from an intensive treatment approach. They often receive either best supportive care (BSC), low dose treatment such as Low Dose Ara-C (LDAC), or clinical trials of novel agents. In one of the few randomised studies where patients were prospectively considered likely to be unfit for intensive therapy, LDAC was superior to BSC with 18% v 1% patients achieving CR. No patients with high risk cytogenetics (Grimwade 1998), achieved CR (Burnett 2007). Laromustine (Cloretazine®) is a novel sulfonylhydrazine alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links. Laromustine has previously shown clinical activity in patients with de novo AML and high risk MDS (Giles et al. JCO 2007). A confirmatory phase II study of single agent laromustine was conducted in previously untreated patients ≥ 60 years old with de novo AML, prospectively considered likely to be unfit for intensive chemotherapy. Patients had at least one poor risk factor, defined by age ≥70, performance status 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Eighty-five patients received induction therapy with 600 mg/m2 laromustine. Second induction cycles were administered in 14 patients after partial response or hematologic improvement. Eighteen patients received at least one consolidation cycle of cytarabine 400 mg/m2/day CIV for 5 days. Methods: A retrospective non-randomised comparison was performed between the 85 patients treated with laromustine, and 121 patients satisfying the same entry criteria, treated in the AML 14 trial with either BSC or LDAC. Outcomes were compared using Mantel-Haenszel and logrank methods for unadjusted comparisons, and regression methods for adjusted analyses. Results : Patients in AML14 were slightly older than those treated with laromustine (median age 75 v 73), and tended to have higher white blood cell counts; by contrast, there were significantly fewer cardiac or respiratory comorbidities reported in the AML14 population. Other important risk factors such as performance status and cytogenetics were similar between the groups. Responses overall (CR/CRp) were seen in 33% (28/85) of patients treated with laromustine, compared with 2% (1/60) and 23% (14/61) in patients treated with BSC and LDAC (p<0.0001, p=0.2, respectively). In particular, 1 patient with −5/del(5q), and 3 patients with −7/del(7q) cytogenetics experienced a CR with laromustine; patients in AML 14 with adverse cytogenetics saw no remissions. Survival was significantly improved in the laromustine group compared to BSC (1 year survival 20% v 8%, unadjusted HR 0.58 [0.40–0.84] p=0.004), and roughly comparable to that of LDAC (1 year survival 20% v 25%, HR 1.04 [0.73–1.49] p=0.8). Analyses adjusted for differences in baseline demographics, and using propensity scores gave consistent figures. Conclusions: Retrospective comparison of unrandomised data has significant limitations even though care has been taken to match for factors known to be predictive for survival. Laromustine was able to achieve a higher CR rate than LDAC or BSC, and produced remissions in groups where no remissions have previously been seen with LDAC or BSC. Laromustine gave significantly better survival than BSC, and demonstrated similar survival to LDAC.

UK Estimates of Burden of Disease Associated with Management of Intermediate-2 or High-Risk Myelodysplastic Syndromes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4749-4749
Author(s):  
Nic Brereton ◽  
Lars Nicklasson ◽  
Ghulam J. Mufti
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Economic Analysis ◽  
Myelodysplastic Syndromes ◽  
Burden Of Disease ◽  
Standard Care ◽  
Economic Evaluations ◽  
Blood Transfusions ◽  
Haematological Cancer ◽  
The Uk

Abstract Abstract 4749 BACKGROUND: Previous UK studies into the burden of disease (BoD) of intermediate-2 (INT-2) or high-risk myelodysplastic syndromes (MDS) have focused on the potential budget impact of azacitidine. No estimates have been published for the UK that incorporate the costs associated with basic disease management in the UK for this group of patients. OBJECTIVE: To estimate the annual burden of MDS in the UK. METHODS: The research comprised a systematic review of studies in haematological cancer, and a subsequent economic analysis. The systematic review extracted all relevant BoD information from identified papers, including not only patient or healthcare elements, but also the burden on carers and family. The economic analysis combined all available, relevant evidence into annual, UK-specific cost estimates. RESULTS: The systematic literature review identified and extracted information from 23 papers. Study designs were comprised of economic evaluations (n=6), observational studies (n=2), RCTs (n=2), retrospective analyses involving registries or hospital data (n=6), review articles (n=3) and surveys (n=4). The National Institute for Health and Clinical Excellence appraisal of azacitidine was also included as was information from the pivotal trial of azacitidine, AZA-001. Across the literature reviewed, three main types of standard care were identified: supportive care (SC) alone, low-dose chemotherapy (LDC) and, more rarely, standard dose chemotherapy (SDC). Many papers provided estimates of transfusion burden, which had the largest BoD impact in patients who were considered transfusion dependent. Use of erythropoiesis-stimulating agents was identified as an additional important resource, and the societal burden of haematological cancer was also quantified in one study, which examined time required of carers and family for transfusion visits. The most recent UK epidemiological estimates were used to convert average per-patient BoD figures to national estimates. Each type of standard care had a different associated burden of blood transfusions; therefore, the subsequent economic analysis weighted the estimated BoD according to the proportion of patients expected to be eligible for BSC, LDC and SDC. It is expected that 761 INT-2 and high-risk MDS patients will be treated each year. Among these, it was estimated that a total 5,121 blood transfusions would be required per year. These transfusions are expected to be associated with a total UK annual cost of approximately £1.4 million to the NHS, as well as £17,955 to carers and family members based on expected time off work to attend transfusion sessions with the patient. Values ranging between £10 million and £14 million per year were estimated for the likely national BoD on hospitals for inpatient stays, and the national cost of NHS community nurse visits was estimated to be £115,877 per year. The societal cost of inpatient stays was also experimentally calculated based on hospitalisation statistics from the AZA-001 trial; this produced an estimated annual burden of £312,010 for the UK. CONCLUSION: The annual burden of disease associated with MDS in the UK is estimated at between £12 million and £16 million. Major components of this burden include hospitalisation and transfusion costs. Indirect costs associated with MDS such as productivity costs for patients and carers appear relatively modest but are nonetheless an important consideration and should not be overlooked. Disclosures: Brereton: Celgene Ltd: Consultancy. Nicklasson:Celgene Ltd: Employment. Mufti:Celgene: Consultancy, Research Funding.

Novel Strategy for MDS with Thalidomide, 5-Azacitidine and Stem Cell Transplantaion

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4960-4960
Author(s):  
Kunio Hayashi ◽  
Kazuhiro Ikegame ◽  
Hiroyasu Ogawa
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Supportive Care ◽  
Cell Transplantation ◽  
Lower Risk ◽  
Immunosuppressive Agents ◽  
Best Supportive Care ◽  
First Line ◽  
Line Therapy

Abstract Abstract 4960 Background: MDS ‘s clinical pathology is heterogeneous such as the intensity of cytopenia and the rate and the timing of AML evolution. The definite algorithm is difficult to be settled. We have several approved agents as the MDS therapy in Japan, Thalidomide, Lenalidomide and 5-Azacytidine (AZA) in addition to the conventional agents such as immunosuppressive agents (predonisolone and cyclospoline-A) and hematopoietic cytokines (G-CSF, Erythropoietin). We retrospectively analyze 36 MDS patients who were treated since 2004 in our hospital. The first current treatment was the conventional agents and transfusion that we call best supportive care (BSC). Since 2006 we could treat by thalidomide in addition to the conventional ones. Lenalidomide is limited to use only for 5q- MDS that is not included in 36 MDS. It was 2011 that we applied stem cell transplantation (SCT) for AML/MDS (AML evoluted from MDS). This conditioning regimen is low dose or non-myeloablative that is feasible to older individuals. The stem cell source of haploidentical donor or cord blood is immediately available at the time of urgent transplantation. The rate of GVHD of these HLA-mismatch transplantations is not so high as generally thought. The optimal SCT timing is very difficult and important. Patients and methods: In the baseline characteristics of consecutive 36 MDS patients, the median age was 70 (range 39 ∼ 90), F/M was 24/12. The 26 of them were treated by thalidomide daily 50mg∼100mg as the first line therapy, whose diagnosis was RCUD n=6, RARS n=2, RCMD n=9, RAEB-1 n=2 RAEB-2 n=4 and AML/MDS n=3. Using IPSS score, there were 9 patients with low, 6 int-1, 7 int-2 and 4 high (including 3 AML/MDS). 8 int-2 and 1 high had complex karyotype that is cytogenetically high risk. The other 8 patients received the best supportive care (BSC) by immunosuppressive agents, cytokines and transfusion. Two another patients were treated by AZA as the first line. Two of three AML/MDS had received stem cell transplantation (62 years male received haplo-mini SCT and 75 years female received cord blood SCT). Results: Thalidomide produced hematological improvement in 70% of lower IPSS (low and int-1) simultaneously with transfusion independency. On the contrary, int-2 improved only in 14%, high and AML/MDS in 0% (Fig 1). The improvement by thalidomide of RARS was 100% and RCMD was 67%. The p value about the improvement about WHO classification was 0. 182 because of the insufficiency of the number of patients. When the over all survival of thalidomide treated patients is compared with BSC patients, there was no statistically difference between them in lower risk MDS. In higher risk MDS, two int-2 patients who had failed with the single use of thalidomide achieved the hematological improvement by the combination of thalidomide and AZA. One of them was cytogenetically high risk. Their AZA cycles were 14 and 12. They were still receiving AZA. After the long-term follow-up, it will be clear that this combination makes statistical predominant in OS. This combination was completely ineffective against AML/MDS who received stem cell transplantation as second-line therapy. After the transplantation they received AZA maintenance that is expected to suppress minimal residual disease while monitoring WT1 expression. They are alive now for 1. 41 and 1. 01 years since they were diagnosed as AML/MDS. Conclusion: Thalidomide makes good hematological response of lower risk MDS and bring the free of transfusion that elevates and maintains the QOL of the patients. About the higher risk of MDS, thalidomide single therapy has no works but its' combination with AZA is very effective and bring not only the hematological improvement but also the possibility of longer overall survival. For AML/MDS, stem cell transplantation is the only potential curative treatment. Disclosures: No relevant conflicts of interest to declare.

Therapy With Demethylating Agents Significantly Improves Overall- and AML-Free Survival In Patients With MDS Classified As High-Risk By IPSS Or Very High Risk By IPSS-R and Partial Or Total Monosomy 7-Results From a German Multicenter Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2784-2784 ◽  
Author(s):  
Julie Schanz ◽  
Friederike Braulke ◽  
Katayoon Shirneshan ◽  
Kathrin Nachtkamp ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Median Time ◽  
Research Funding ◽  
Risk Group ◽  
Best Supportive Care ◽  
High Risk Group ◽  
Monosomy 7 ◽  
Free Survival ◽  
Very High

Abstract Introduction Total (-7) or partial (7q-) monosomy 7 is frequent in malignant myeloid disorders, observed in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. Monosomy 7 is associated with poor outcome, high susceptibility to infections and poor response to chemotherapy. A therapeutic benefit for 5-azacytidine was previously described (Fenaux et al., 2009). The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with monosomy 7 in a multicentric, retrospective German cohort study. Patients and methods Currently, 231 patients with MDS/AML following MDS and monosomy 7 were included. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, age ≥18 years, bone marrow blast count ≤30% and presence of -7 or 7q-. The data was assembled from centers in Düsseldorf, (n=120; 52%), Cologne (n=38; 17%), Freiburg (n=31; 13%), Göttingen (n=14; 6%), Munich (n=13; 6%), Dresden (n=11; 5%) and Mannheim (n=4; 2%). The median age in the study cohort was 67 years, 65% of patients were males. 29/231 patients (13%) were diagnosed as AML following MDS. MDS/AML was therapy-associated in 24 patients (11%). Regarding IPSS, 38 (19%) were classified as low/intermediate 1 risk and 165 (81%) as intermediate-2/high-risk. According to IPSS-R, 2 (1%) were assigned to the very-low/low risk group, 31 (16%) to the intermediate group, 52 (27%) to the high-risk group and 107 (56%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), demethylating agents (DMA; either 5-azacytidine or decitabine), and others. Results A best supportive care regimen was chosen in nearly half of the patients (49%). The remaining patients received 1-4 sequential therapies (1: 29%; 2: 11%; 3: 10%; 4: 1%). As the first line therapy, 64 patients (54%) received DMA, 24 (20%) an allo-Tx, 9 (8%) HDC, 5 (4%) LDC, and 16 (14%) were treated with other therapies. The best prognosis was observed in patients eligible for allo-Tx: The median OS in transplanted patients was 924 days as compared to 361 days (p<0.01) in patients not eligible for transplantation. In the latter cohort, patients who received DMA at any course of their disease did not differ from those receiving other therapies: The median OS was 468 days in patients treated with DMA as compared to 325 on those with alternative therapies (p not significant) and the median time to AML-transformation was 580 versus 818 days (p not significant), respectively. However, by classifying patients according to IPSS- and IPSS-R, it became obvious that patients with an IPSS high-risk or an IPSS-R very high risk showed a clear benefit from DMA: In the first group, median OS was 444 days in DMA-treated and 201 days in non-DMA-treated patients (p=0.048), in the latter group, median OS 444 days in the DMA-treated and 203 days in the non-DMA treated cohort (p=0.017). Comparable results were observed regarding AML-free survival: Median time to AML was 580 (DMA) vs. 186 (no DMA) days in IPSS high risk patients (p=0.031) and 580 (DMA) vs. 273 (no DMA) days in the IPSS-R very high risk group (p not significant). Conclusions Patients with MDS, partial or total monosomy 7 and a high risk according to IPSS or a very high risk according to IPSS-R show a pronounced benefit when treated with DMA, regarding overall- as well as AML-free survival. Further results from the ongoing data analysis will be presented in detail. The study was supported by research funding from Celgene. Disclosures: Schanz: Celgene: Research Funding. Braulke:Celgene: Research Funding. Germing:Celgene: Honoraria, Research Funding. Schmitz:Novartis: Research Funding; Celegene: Consultancy, Research Funding, Speakers Bureau. Götze:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Research Funding. Haase:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Analysis of the impact of adherence to guidelines and expert advice in patients with myelodysplastic syndromes

2020 ◽  
Author(s):  
A. Kasprzak ◽  
K. Nachtkamp ◽  
M. Kondakci ◽  
T. Schroeder ◽  
G. Kobbe ◽  
...  
Keyword(s):  
Supportive Care ◽  
Myelodysplastic Syndromes ◽  
Treatment Options ◽  
Iron Chelation ◽  
Best Supportive Care ◽  
Expert Advice ◽  
Adherence To Guidelines ◽  
A Prospective Study ◽  
Low Dose Chemotherapy ◽  
The Impact

Abstract The European Leukemia Net (ELN) guidelines for treatment of myelodysplastic syndromes (MDS) connect heterogeneous MDS subgroups with a number of therapeutic options ranging from best supportive care to allogeneic stem cell transplantation (alloSCT). However, it is currently unknown whether adherence to guideline recommendations translates into improved survival. The sizeable database of the Duesseldorf MDS Registry allowed us to address this question. We first performed a retrospective analysis including 1698 patients (cohort 1) to whom we retrospectively applied the ELN guidelines. We compared patients treated according to the guidelines with patients who deviated from it, either because they received a certain treatment though it was not recommended or because they did not receive that treatment despite being eligible. We also performed a prospective study with 381 patients (cohort 2) who were seen in our department and received guideline-based expert advice. Again, we compared the impact of subsequent guideline-adherent versus non-adherent treatment. For the majority of treatment options (best supportive care, lenalidomide, hypomethylating agents, low-dose chemotherapy, and intensive chemotherapy), we found that adherence to the ELN guidelines did not improve survival in cohort 1. The same was true when patient management was prospectively enhanced through guideline-based treatment advice given by MDS experts (cohort 2). The only exceptions were alloSCT and iron chelation (ICT). Patients receiving ICT and alloSCT as recommended fared significantly better than those who were eligible but received other treatment. Our analysis underscores the limited survival impact of most MDS therapies and suggests to pursue alloSCT in all suitable candidates.

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