Cost Burden Analysis of Ineffective Induction Chemotherapy in Elderly Patients with AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4531-4531
Author(s):  
Aileen Cleary Cohen ◽  
Nancy Davidson ◽  
Jason Scharf ◽  
Derek Middlebrook

Abstract Abstract 4531 Introduction According to the Surveillance, Epidemiology, and End Results (SEER) database 12,810 patients will be diagnosed with acute myeloid leukemia (AML) in 2009 with an incidence rate of 3.5 per 100,000 persons in the United States. The SEER data estimates that 55% of those diagnosed are 65 years or older. Standard first line therapy for the treatment of AML consists of at least one round of chemotherapy commonly referred to as induction. A significant portion of those patients who receive standard induction chemotherapy will have leukemia that fails to show a complete response as defined by less than 5% leukemia blasts in the bone marrow with normal tri-lineage hematopoiesis and peripheral blood count recovery (Mueller S, et al. BMC Cancer 2006, 6:143). Age, patient performance status, the presence of secondary AML, cytogenetics, and molecular markers are prognostic for particular cohorts of patients, however, there is currently no means to predict whether an individual's leukemia will or will not undergo a complete response (CR) after the administration of standard AML induction chemotherapy. Methods A budget impact model was designed to assess the incremental societal cost and incremental cost to a typical national health plan of treating patients who will fail induction therapy. The analysis only evaluated elderly patients over the age of sixty five. Data were gathered from the peer reviewed literature. All costs have been updated to 2009 dollars using the medical care component of the consumer price index. The patient population was determined to be 6,981 patients in 2009 with 30% receiving induction therapy (Menzin J, et al. Arch Intern Med. 2002; 162:1597-1603) and only 38% demonstrating a CR (Appelbaum FR, et al. Blood 2006 107:3481-5) resulting in 1,303 patients failing during induction therapy. The costs were taken from Menzin et al., which used Medicare claims data to determine the associated costs of AML patients during the first two years post diagnosis. In the model Medicare payments are used as a proxy for direct costs to society and a national health plan. These reimbursements are able to capture the costs of the initial hospital visit, lab/diagnostic/radiology, supportive care, drugs, and adverse events through the observation of payments across all appropriate settings of care (inpatient hospitalization, skilled nursing facility, outpatient hospital/clinical, physician's office, home health, and hospice). A patient undergoing chemotherapy incurred costs of $120,468 over two years, while a patient avoiding chemotherapy only incurred costs of $40,720. Results The incremental cost of a patient receiving induction therapy was calculated to be $79,748. For a national health care plan with an assumed average of one million members results in a cost of $283,856 to treat patients whose leukemia would not respond to induction chemotherapy. The overall societal impact of treating this patient population with ineffective therapy is $104 million. Conclusions Patients who are subjected to ineffective chemotherapy face the cytotoxic effects of the treatment, none of the benefits of treatment response, and impose a significant cost burden to themselves and the healthcare payment system. Diagnostics currently in development that can identify patients at the time of diagnosis with disease unresponsive to therapy may have the ability to alleviate unnecessary costs, while steering patients to better tailored and more effective therapies. Disclosures: Cleary Cohen: Nodality, Inc: Employment. Middlebrook:Nodality Inc: Employment.

2007 ◽  
Vol 25 (31) ◽  
pp. 4909-4913 ◽  
Author(s):  
Megan Burke ◽  
James R. Anderson ◽  
Simon C. Kao ◽  
David Rodeberg ◽  
Stephen J. Qualman ◽  
...  

Purpose Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS. Patients and Methods We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response. Results Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS. Conclusion In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.


The Lancet ◽  
1998 ◽  
Vol 352 (9122) ◽  
pp. 125 ◽  
Author(s):  
Bruno Simini

Challenge ◽  
1979 ◽  
Vol 22 (3) ◽  
pp. 11-16
Author(s):  
Jimmy Carter

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 904-904 ◽  
Author(s):  
Naval Daver ◽  
Hagop M. Kantarjian ◽  
Gail J. Roboz ◽  
Patricia L. Kropf ◽  
Karen W.L. Yee ◽  
...  

Abstract Introduction: Guadecitabine (SGI-110) is a novel next-generation hypomethylating agent (HMA) administered as a small volume subcutaneous (SC) injection which results in extended decitabine exposure. Phase 2 study has been conducted in r/r AML patients using two different doses and schedules of guadecitabine. We report here long term survival and clinical complete response rates in various prognostic subgroups of r/r AML patients Methods: r/r AML patients who were either refractory to or relapsed after induction chemotherapy were enrolled in this Phase 2 study. In the first cohort, patients were randomized (1:1) to either 60 mg/m2/d or 90 mg/m2/d on Days 1-5 (5-day regimen). In the second cohort, patients were assigned to treatment with 60 mg/m2/d on Days 1-5 and Days 8-12 (10-day regimen) for up to 4 cycles, followed by 60 mg/m2/d Days 1-5 in subsequent cycles. Cycles were scheduled every 28 days for both regimens with dose reductions/delays allowed based on response and tolerability. Patients remained on treatment as long as they continued to benefit without unacceptable toxicity. The primary endpoint was the composite Complete Response (CRc) rate: CR + CR with incomplete platelet recovery and normal neutrophils count (CRp) + CR with incomplete neutrophil recovery (CRi) using modified International Working Group (IWG) criteria (Cheson et al, 2003). Secondary endpoints included overall survival (OS), and safety as measured by Adverse Events (AEs) using CTCAE v4.0, and early 30 and 60-day all-cause mortality. Individual dose and schedule results were previously reported (Roboz et al, European Society of Medical Oncology, 2014) where there was no difference between the 2 doses of 60 and 90 mg/m2/d and a trend of higher CRc and CR for the 10-day initial intensification regimen. We report here long tem survival and CRc data in various prognostic subgroups in the overall r/r AML patient population treated with guadecitabine. Results: 103 r/r AML patients were treated with guadecitabine (50 with 5-day regimen and 53 with the initial 10-day intensification regimen). Eight six patients (84%) received prior standard 7+3 induction; 15 patients (14%) received other prior induction chemotherapy regimens mostly with high dose cytarabine; clofarabine or cladribine with or without cytarabine; and only 2 patients (2%) received HMA as prior front line induction treatment. Median age was 60y (range 22-82y); male 60%; PS 2 in 14%; poor risk cytogenetics 41%; prior Hematopoietic Cell Transplant (HCT) 18%, and median number of 2 prior regimens (range 1-10) including 11% with prior HMA treatment. CRc was achieved in 24 patients (23%). After a median follow up of 29 months, the median OS was 6.6 months with 1-y and 2-y survival rates of 28 and 19% respectively. CRc was associated with statistically significant longer survival; median OS not reached for patients in CRc and was 5.6 months for patients with no CRc (p<0.01). Table 1 shows CRc rates and Median OS in some of the standard prognostic subgroups. Clinical activity in terms of CRc was observed in all subgroups with no statistically significant difference between any of the prognostic subgroups examined based on age; PS; cytogenetics risk; prior HCT; and time from last therapy. However OS was significantly worse in patients with PS 2 (p<0.001); patient with poor risk cytogenetics (p<0.001); and those with <6 months from last therapy (p=0.015). Safety was acceptable in all doses and schedules, the most common Grade ≥3 AEs regardless of relationship to therapy were febrile neutropenia (60%), pneumonia and thrombocytopenia (36% each), and anemia (31%). All-cause early mortality was relatively low for this patient population with 3.8% at 30 days and 11.6% at 60 days in all guadecitabine treated patients with no higher mortality with the 10-day initial intensification regimen. Conclusions: Guadecitabine showed good clinically activity in terms of CRc with acceptable safety profile in r/r AML patients with various standard poor prognostic factors. CRc with guadecitabine was associated with longer survival. While CRc was observed in all subgroups, patients with poor PS; poor risk cytogenetics; or with short time from last therapy had significantly worse survival. A randomized phase 3 study is being initiated with guadecitabine using the 10-day initial intensification regimen vs Treatment Choice in r/r AML patients. Disclosures Daver: Sunesis: Consultancy, Research Funding; Ariad: Research Funding; Karyopharm: Honoraria, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Kiromic: Research Funding; Otsuka: Consultancy, Honoraria. Kantarjian:Amgen: Research Funding; Bristol-Myers Squibb: Research Funding; ARIAD: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Kropf:Celgene: Consultancy; Takeda: Consultancy. Yee:Novartis Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Su:Astex Pharmaceuticals, Inc.: Employment. Azab:Astex Pharmaceuticals, Inc.: Employment. Issa:Astex Pharmaceuticals, Inc.: Consultancy; Teva: Consultancy.


1993 ◽  
Vol 4 (3) ◽  
pp. 344-348
Author(s):  
Richard Enochs ◽  
Amy Cato ◽  
Irene Jillson-Boostrom ◽  
Gordon Bonnyman ◽  
Ronald Braithwaite ◽  
...  

2012 ◽  
Vol 38 (2) ◽  
pp. 43-46 ◽  
Author(s):  
N Islam ◽  
MM Rahman ◽  
MA Aziz ◽  
F Begum ◽  
ABM Yunus

Cure rates for adult acute lymphoblastic leukaemia (ALL) in developing countries are significantly lower because of problems unique to these countries. Recent studies have reported complete response rates for any induction regimen of more than 90% in adult ALL patients. This study was conducted to evaluate the response rate of induction chemotherapy in adult ALL patients in the Department of Haematology, Bangabandhu Sheikh Mujib Medical University, from January 2007 to December 2008.  In this observational study, 35 newly diagnosed ALL patients classified either as L1/L2 according to  French-American-British (FAB) classification, aged between 15 to 60 years were assigned for  induction therapy with modified MRC UKALL XII/ECOG E2993 protocol. But ultimately 30 patients completed therapy and available for statistical analysis. Among the studied 30 cases 12(40%) patients after phase 1 and overall 24(80%) patients after phase 2 induction therapy, achieved morphologic complete remission (CR). After phase 2 therapy 6(20%) patients fell in the group of non responders (NR) as the blast percentage was ?5% at the time of bone marrow evaluation. This study shows the response rates in adult ALL with induction therapy slightly below the anticipated response rates of developed countries which may be due to little modification of the original protocol. DOI: http://dx.doi.org/10.3329/bmrcb.v38i2.12879 Bangladesh Med Res Counc Bull 2012; 38: 43-46


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