Study of Imatinib Treatment Patterns and Outcomes Among US Veteran Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia

Size: px
Start display at page:

Download "Study of Imatinib Treatment Patterns and Outcomes Among US Veteran Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia"

Transcription

1 Health Care Delivery Original Contribution Study of Imatinib Treatment Patterns and Outcomes Among US Veteran Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia By Nancy Vander Velde, MD, Lei Chen, MD, PhD, Amy Guo, PhD, Hari Sharma, Maryna Marynchenko, MBA, Eric Q. Wu, PhD, Jinan Liu, PhD, Heidi Yang, MPH, and Lizheng Shi, PhD Tulane University; Southeast Louisiana Veterans Health Care System, New Orleans, LA; Novartis Pharmaceuticals Corporation, East Hanover, NJ; and Analysis Group, Boston, MA Abstract Purpose: This study investigated the treatment patterns and outcomes for US veteran patients with chronic myeloid leukemia chronic phase (CML-CP) initiated on imatinib (IM). Patients and Methods: Patients (age 18 years) with at least one CML diagnosis (International Classification of Diseases, Ninth Edition Clinical Modification: 205.1x) during the period January 1, 2000, to June 30, 2011, and initiated on IM as first-line therapy were identified in the VISN 16 data warehouse (N 137). Accelerated and blastic phases (AP/BP) were identified on the basis of WHO classification using complete blood count (CBC) data. Rates of IM dose adjustment, discontinuation, and switching to another drug therapy were estimated. Time to discontinuation, progression to AP/ BP, and survival were assessed using Kaplan-Meier analysis (KM). Results: During follow-up, 19.0% of patients had at least one dose increase; of these, 19.2% switched to another therapy. Dose reductions occurred in 25.6% of patients. Among patients who discontinued IM (n 74; 54.0%), whereas 16.2% switched to other therapies, 27.0% neither restarted IM nor switched to other therapies. KM showed that 25.6% and 42.4% of patients discontinued IM treatment by year 1 and 2, and 8.1% and 16.0% demonstrated disease progression by year 1 and 2, respectively. Among patients who experienced disease progression (n 28), 32.1% continued IM postprogression, 32.1% discontinued IM before progression, 28.6% discontinued IM postprogression without switching, and 7.1% switched to other therapies postprogression. The mortality rates were 3.0% and 9.5% after IM initiation, and 21.7% and 42.7% after disease progression by year 1 and 2, respectively. Conclusion: In this veteran population, a substantial number of IM-treated patients, including those with disease progression, either discontinued or interrupted IM use without switching to other therapies. Introduction Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disease resulting from DNA damage, and leading to the formation of the fusion gene BCR-ABL, which encodes a constitutively active tyrosine kinase. 1,2 CML accounts for 11.3% of all new leukemia cases, 3 with an annual incidence of approximately 4,800 cases in the United States alone. 3,4 The disease is usually diagnosed during a prolonged chronic phase in which most patients experience mild symptoms of fatigue, anorexia, and weight loss 2 ; overall survival rates from diagnosis of CML have been reported at 80% to 85% in 7- to 10-year periods. 5 Patients may, however, eventually progress to an accelerated phase characterized by rising numbers of poorly differentiated cells in the peripheral blood and bone marrow, a phase that can last for approximately 6 months before advancing to a rapidly fatal blastic phase. 6 Therapeutic options for CML vary according to disease phase, prior treatment history and outcomes, and other prognostic factors. Imatinib (IM), the prototype BCR-ABL tyrosine kinase inhibitor (TKI), received FDA approval in 2001 and has largely replaced conventional drug therapy (eg, interferon-alfa and hydroxyurea) as the first-line therapy for newly diagnosed CML chronic phase (CML-CP). The standard starting dose of IM for the chronic phase is 400 mg daily, with a recommended reduction to 300 mg in the event of toxicity. 7 IM induces complete cytogenetic response in a majority of newly diagnosed patients, 8 and has vastly improved survival in CML. 4 However, a subset of patients exhibit poor response or experience relapse despite standard-dose IM treatment. 9,10 Resistance to IM can occur as a result of amplification or mutation of the BCR-ABL gene, or through other mechanisms independent of BCR- ABL. 11 Dose escalation to 600 mg or 800 mg is considered one acceptable approach in this setting, though the observed benefits of dose increase have varied substantially. 7,10 Alternative options include switching to nilotinib or dasatinib, more potent second-generation TKIs, which have since been approved for newly diagnosed and IM-resistant or -intolerant CML. Although no improvement in overall survival compared with imatinib has been demonstrated in clinical trials, treatments with nilotinib or dasatinib are associated with higher rates of achieving major molecular responses (defined as 3 log reduction in BCR-ABL transcript level based on the International Scale). 12,13 In addition, fewer patients treated with nilotinib experienced progression to accelerated or blastic phase (AP/BP) when compared with patients treated with imatinib. 13 Nilotinib and dasatinib are active against many IM-resistant mutations of the BCR-ABL kinase domain, 14 have demonstrated superior efficacy to IM as first-line therapies in the jop.ascopubs.org 1

2 Vander Velde et al chronic phase, 15,16 and are effective after prior failure with standard- or high-dose IM therapy. 17,18 Consequently, National Comprehensive Cancer Network guidelines recommend switching to a second-generation TKI in patients with IM resistance or intolerance in the chronic phase. These drugs may also be appropriate for IM-treated patients who have progressed to an advanced phase, potentially combined with chemotherapy followed by stem-cell transplantation in the case of CML-BP. 7 In view of clinical data and guideline recommendations, research is warranted to identify usage patterns associated with first-line IM therapy and to examine the uptake of new TKIs as second-line options in clinical practice. Using retrospective health records, the present study sought to characterize treatment patterns and clinical end points among US veterans with chronic-phase CML receiving first-line IM therapy, including dose adjustments, therapy discontinuation or interruption, therapy switching, progression to advanced phases of CML, and mortality. Patients and Methods Data Source This observational study was conducted using electronic medical records from the South Central Veterans Affairs Health Care Network (VISN 16) data warehouse. The VISN 16 data warehouse is an integrated, de-identified, individual-level database that includes records for more than 445,000 veterans located in Arkansas, Louisiana, Mississippi, Oklahoma, and parts of Alabama, Florida, Missouri, and Texas. The health care network represents 10 medical centers and 40 community-based outpatient clinics. The database contains demographic data, medical records, pharmacy prescriptions, CBC data, and mortality information (date of death). Data covering the period from January 1, 2000, to June 30, 2011, were used for analysis. Sample Selection Eligible patients had at least one diagnostic code for CML (International Classification of Disease-9-Clinical Modification: 205.1x) in their medical records between January 1, 2000, and June 30, The date of the first CML diagnosis was defined as the index date. As of the index date, included patients were 18 years of age and were in CML-CP, identified by the absence of any evidence suggesting AP/BP disease in patients CBC data within 30 days around the index date. An algorithm to identify CML disease phase was based on the WHO classification of myeloproliferative diseases and the availability of data. Accelerated-phase CML (CML-AP) was detected on the basis of any of the following: (1) presence of 10% to 19% myeloblasts (a unipotent stem cell that differentiates into one of the actors of the granular series) in the peripheral blood, (2) presence of more than 20% basophils (the least common of the granucocytes) in the peripheral blood, (3) presence of platelet counts less than 100,000/ L, or (4) presence of platelet counts more than 1,000,000/ L. Blastic-phase CML (CML-BP) was identified by the presence of 20% myeloblasts or lymphoblasts in bone marrow or peripheral blood. 19 Finally, analyses were restricted to patients who received first-line IM therapy for CML on or after the index date, excluding patients with prescription fills for interferon-alfa, hydroxyurea, nilotinib, or dasatinib before IM initiation. Study Outcomes and Analyses IM treatment patterns were assessed after initiation of first-line IM therapy and included discontinuation or interruption, therapy switching, and dose adjustments. IM discontinuation was defined as having no available IM supply for 60 days during follow-up, as indicated by IM fill dates and days of supply in patients prescription drug records. Therapy switching, a subcategory of discontinuation, was identified by the use of a different CML drug (interferon-alfa, hydroxyurea, nilotinib, or dasatinib) after IM discontinuation. Time to discontinuation from IM initiation was evaluated using Kaplan-Meier survival analysis (KM); patients were censored at death or at the end of data availability. In addition, the overall proportion of patients who discontinued IM at any point was described; days to IM discontinuation, rates of IM reinitiation, and therapy switching were computed within this subgroup. IM dose increase was defined as any increase from a starting dose of 400 mg to 600 mg daily, or from more than 400 to 600 mg to 800 mg daily. This definition is based on the standard dose increases considered in the clinical trial setting (ie, 400 to 800 mg or 300 to 600 mg), 10 but allows for possible variations on these dose escalation protocols in line with the approved labeling in clinical settings. Conversely, dose reductions included any decrease in daily dose by 100 mg relative to the starting dose, where 100 mg represents the difference between 400 mg (standard-dose IM) and 300 mg (recommended for patients with dose-limiting adverse events). 7 Rates of IM dose adjustments were calculated within the study sample. Among patients who received dose increases, time to any dose increase, duration at higher dose, rate of subsequent therapy switching, and time to therapy switching were assessed. The KM method was applied to study clinical end points including disease progression to CML-AP/BP, overall mortality, and postprogression mortality. Time to progression and overall mortality were measured from IM initiation, whereas mortality among patients with disease progression was measured from the progression date. In addition, the patterns of IM discontinuation with or without therapy switching, length (in days) to disease progression, and median survival after progression were described in the subgroup of patients who experienced disease progression. Results Sample Characteristics A total of 512 veterans with one or more CML diagnoses were identified in the VISN 16 database, the majority of whom (63.1%) were initially diagnosed in the chronic phase. Among the veterans with chronic-phase CML, only 169 patients received IM therapy on or after the diagnosis; the final study 2 JOURNAL OF ONCOLOGY PRACTICE

3 Imatinib Treatment in Ph CML sample included 137 individuals who received first-line therapy with IM on or after diagnosis (Appendix Figure A1, online only). Demographic characteristics of patients as of the index date are summarized in Appendix Table 1 (online only). Average age at first CML diagnosis was years, 96.4% of veterans were male, 64.2% were diagnosed during or after 2005, and average length of follow-up in the database was 4 years from the CML diagnosis. Dose Adjustments of IM Imatinib dose increases occurred in 26 patients (19.0% of the population), with a median time to increase of 400 days from initiation (Table 1). Most dose increases (n 23; 16.8%) occurred in patients initiated on standard or below-standard dosages ( 400 mg); doses were increased to 600 mg daily. Of the 26 patients with dose increase, five (19.2%) were switched to a different CML drug therapy after IM dose increase, with a median time to therapy switching of 1,315 days. Decreases in IM daily dosage were observed in 25.6% of patients (Table 1). In addition, 54.3% of all dose reductions were from the standard dose of 400 mg to 300 mg daily. Discontinuation or Interruption of IM Based on KM analysis, rates of IM discontinuation were 25.6% at 1 year and 42.4% at 2 years (Figure 1). Overall, 54.0% of veterans (n 74) discontinued IM at some point during follow-up, with median time to discontinuation of 395 days (Table 1). Within the subgroup of patients who discontinued IM, 47.3% reinitiated IM and16.2% switched to another CML drug; 9 of 12 patients who switched received second-generation TKI. Over one quarter (27%) of discontinuers neither restarted IM nor switched to a different drug for CML. Disease Progression and Mortality Disease progression to CML-AP/BP after IM initiation was 8.1% by 1 year and 16.0% by 2 years (Figure 2). Approximately 20.4% of patients experienced CML progression, with median time to disease progression of 446 days after IM initiation (Table 1). Among the 28 patients with disease progression, nine (32.1%) had discontinued IM before progression, and another nine (32.1%) continued to receive IM until the end of followup. In addition, eight patients (28.6%) discontinued IM after progression without switching to another therapy, and two (7.1%) discontinued IM and switched therapies postprogression; one patient received a second-generation TKI. In the full study sample (N 137), mortality rates from any cause were 3.0% at 1 year and 9.5% at 2 years from IM initiation (Appendix Figure A2, online only). Among patients who advanced to CML-AP/BP, any-cause mortality rates were 21.7% at 1 year and 42.7% at 2 years from the date of disease progression (Appendix Figure A3, online only). Discussion This observational study described treatment patterns and disease outcomes for a cohort of US veterans who were diagnosed with CML-CP and received first-line IM therapy. High rates of dose increase and discontinuation or interruption of IM treatment were observed in the years after IM initiation, which corroborates findings from previous analyses among IM-treated patients in Europe. 20,21 Decreases in IM dosage were also common (especially from 400 mg to 300 mg daily), a pattern that likely reflects dose adjustments to achieve better tolerability. 22 In contrast, few patients were observed switching to newer TKIs for CML, even among those who showed a progression to AP/BP. Among the 323 patients with CML-CP identified in the study, only 137 (42.4%) patients received IM as first-line therapy. Although this is in line with another study that found that 42.5% of CML-CP patients had first-line IM therapy, 23 the low use of IM as first-line therapy seems surprising, given that the majority (97.1%) of our patients were diagnosed with CML during or after 2001, the year IM was approved for the treatment of newly diagnosed CML. Most patients (54.0%) discontinued IM treatment at least once during the follow-up. A small proportion (16.2%) of patients in this study switched to other drugs therapies for CML on IM discontinuation, and 18.9% of the patients were already using other drugs before discontinuation and continued to use them after discontinuation. Among the 137 study participants, 35 (25.5%) restarted IM after discontinuation. Although we do not know the reasons for temporary discontinuation in our study, one European cohort study found that 23% of patients receiving IM temporarily discontinued as a result of toxicity. 21 Conversely, more than one half of discontinuers did not restart IM after the initial IM cease, including 27.0% who neither restarted IM nor filled prescriptions for other CML therapies. The study could not confirm reasons for stopping therapy, but they could include IM resistance, intolerance, or noncompliance. In a previous study, 34% of patients who received IM were no longer on treatment at 6 years, and common reasons for discontinuation included unsatisfactory therapeutic effect, adverse events, and withdrawal of consent. 24 Permanent IM discontinuation could also be a nonstandard treatment strategy (eg, some patients may have been purposefully taken off all therapeutic interventions after achieving molecular remission.). However, this strategy is not currently recommended outside of the clinical trial setting 7 because of contradictory evidence mitigating the acceptability of IM discontinuation in patients with molecular remission Patients eligible for care in the Veterans Affairs (VA) system can have private or other public insurances (eg, Medicare) and could use outside facilities for treatments, which can partially explain the discontinuation of IM. However, given the high copays for drugs under Medicare or private insurance, patients tend to use VA system to get medications. Although IM has greatly improved the health outcomes and prognosis of patients with CML, some individuals experience primary resistance or relapse under the standard dose. 9 Approaches for overcoming IM resistance include IM dose increase or switching to a second-generation TKI. Within the VA study sample, an increase in IM dose appeared to be the more common therapeutic approach. During the 48-month follow- jop.ascopubs.org 3

4 Vander Velde et al Table 1. Dose Adjustment, Treatment Discontinuation or Interruption, Disease Progression, and Switching After IM Initiation Patients (N 137) Treatment Patterns No. % Dose adjustments and switching Dose increase from 400 mg to 600 mg daily dose Switching to other therapy after dose increase Dose increase from 400 dose 600 mg to 800 mg daily dose Switching to other therapy after dose increase 0 0 Any dose increase (from 400 to 600 or 400 dose 600 to 800) Switching to other therapy after dose increase Days to any dose increase from IM initiation (to 600 or 800 mg) Median 400 Range 5-1,382 Days of therapy at higher dose from dose increase Median 48 Range 3-2,138 Days to switching to other therapies from dose increase Median 1,315 Range 895-2,519 Dose decrease by 100 mg daily dose compared with starting dose Starting dose 200 mg Starting dose 400 mg Starting dose 600 mg Starting dose 800 mg IM treatment discontinuation/interruption and switching Treatment discontinuation Switching to other therapy after discontinuation Switched to nilotinib or dasatinib Restarting IM therapy after discontinuation Use of other drugs prior to and after discontinuation of IM therapy No restarting of IM therapy or use of other drugs after discontinuation Days to treatment discontinuation from IM initiation Median 395 Range 31-2,056 Disease progression and switching Continued IM use after progression without switching Discontinued IM use prior to progression Discontinued IM use after progression without switching Discontinued IM use after progression with switching Switched to nilotinib or dasatinib Days to disease progression from IM initiation Median 446 Range 0-2,590 Survival days from disease progression* Median 661 Range 0-3,425 Abbreviation: IM, imatinib. *Survival days were measured from the date of disease progression to death, or the end of data, whichever occurred earlier. up, dose increase occurred in 19.0% of patients, and of these, 19.2% subsequently switched to an alternative therapy. Prior research has suggested that increasing the IM dose is effective for some patients with IM-resistant disease. 10 In a clinical trial study, increasing the dose to 600 or 800 mg daily among patients receiving standard-dose IM who experienced hematologic or cytogenetic failure resulted in 40% of patients achieving complete cytogenetic response, and 88% of patients 4 JOURNAL OF ONCOLOGY PRACTICE

5 Imatinib Treatment in Ph CML IM Discontinuation Rate (%) By the end of Year 1 Year 2 IM discontinuation 25.6% 42.4% Time Since Imatinib Initiation Date (days) Figure 1. Time to imatinib (IM) discontinuation, Kaplan-Meier analysis. Disease Progression Rate (%) By the end of Year 1 Year 2 disease progression 8.1% 16.0% Time Since Imatinib Initiation Date (days) Figure 2. Time to disease progression, Kaplan-Meier analysis. with major cytogenetic response maintaining this response beyond 2 years. 10 However, the study found that highest response rates were observed in patients who had previously achieved cytogenetic response with the standard dose; the authors also noted that patients with hematologic failure or those who had never achieved cytogenetic response were less likely to benefit from dose escalation. The notably higher frequency of dose increase compared with therapy switching in the present study may suggest a need for better identification of patients that may not respond to higher dose IM. In this study, 16.0% of patients experienced disease progression by 2 years. Although it is difficult to compare disease progression rates from other studies because of differences in design, treatment settings, and methodology, only 9% of the patients using imatinib had disease progression in a populationbased study conducted in the northwest of England. 28 Switching to a second-generation TKI at disease progression was also rare; a large proportion of patients with disease progression continued to use IM (32.1%) or discontinued IM without switching (28.6%) after disease progression. These results should be considered alongside available clinical data on the efficacy of nilotinib and dasatinib as second-line therapies in patients with IM resistance or intolerance, as second-generation TKIs are efficacious for IM-resistant CML-AP/BP. In a phase II study of patients with CML-CP and IM failure (n 321), nilotinib yielded major cytogenetic response and complete cytogenetic response in 59% and 44% of patients, respectively, at 24 months. 17 With a median follow-up of 15.2 months (n 387), dasatinib showed similar major and complete cytogenetic response rates of 59% and 49% among patients who were resistant or intolerant, respectively, to imatinib. 18 Of note, 72% of the patients in the nilotinib trial 17 and 55% of the patients in the dasatinib trial 18 experienced treatment failure with highdose IM ( 600 mg), indicating that switching to a secondgeneration TKI may be a viable strategy after poor response to IM dose optimization. In phase I studies of nilotinib 29 and dasatinib 30 after IM failure, both drugs induced sizable hematologic and cytogenetic response rates in all phases of CML. Overall, observed rates of therapy switching suggest possible gaps between clinical practice patterns and treatment guidelines 7 regarding the use of second-generation TKIs for CML, particularly among patients with disease progression. Underlying reasons for not switching treatments were unavailable in the database but could include insurance coverage restrictions and cost concerns from the patient s perspective, less familiarity with second-generation TKIs among prescribers, and individual clinical considerations (eg, poor prognosis, contraindications). Second-generation TKIs are not in the VA formulary, but physicians can order these drugs for justified treatment strategies and generally get approved within a matter of days. Because the VA covers the drug costs, it is unlikely that patients did not get second-generation TKIs because these drugs were not in the VA formulary. Future research based on medical chart reviews and clinician surveys would be useful in identifying and overcoming barriers currently preventing the use of other treatment options in patients with CML who are intolerant or resistant to IM therapy. Limitations This study is subject to some limitations, including the general limitations of observational, retrospective data analyses. Medical services provided outside of the VA health system would not be recorded in the electronic health data and may partially explain the lack of treatment among those who discontinued IM. However, patients in the VA system are less likely to use outside resources, and the effect of this limitation is expected to be minimal. As with many other studies using electronic medical record data, this study did not have access to medical charts and had to rely on dispensed prescriptions to determine dose modifications and other outcomes. The data did not have information on hematologic and cytogenetic responses or the monitoring of patients, and thus, the clinician s rationale for patient-specific treatment decisions is unclear. Dasatinib was approved for CML treatment in 2006 and nilotinib in 2007, thus these drugs were not available throughout the study period. However, the average follow-up period was approximately 4 years, and most patients had access to second-generation TKIs during the study period. Although CML has a higher incidence in men than in women, 31 the proportion of male patients in the current sample (96.4%) is considerably larger than in the general diseased population. Finally, as a result of the limited availability of bone marrow test results in VISN 16, identification of disease phase was instead based on peripheral blood findings. jop.ascopubs.org 5

6 Vander Velde et al Conclusion In this retrospective, observational analysis of US veterans in the south central region with CML-CP, a large proportion of patients required dose adjustments to their first-line IM therapy. Although a half of the patient population discontinued or temporarily stopped IM treatment during follow-up, switching to a second-generation TKI was uncommon, even among patients with disease progression. These data indicate potential opportunities for optimizing CML management in VA clinical practice. Further research based on primary data collection in the VA would be beneficial to elucidate reasons for the observed treatment patterns and identify actual barriers to the implementation of clinical guidelines in CML. Acknowledgment Supported by Novartis Pharmaceuticals Corporation. Previously presented at the Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2012, and at the European School of Hematology International Conference on Chronic Myeloid Leukemia, Baltimore, MD, September 20-23, We thank Arielle Bensimon, Analysis Group, for the support in writing this article. In addition, we thank the Department of Veterans Affairs VISN 16 data warehouse for the de-identified data set and the Southeast Louisiana Veterans Health Care System for additional resources. Lizheng Shi has access to the original data and serves as the guarantor for the scientific integrity of the manuscript. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a U are those for which no compensation was received; those relationships marked with a C were compensated. For a detailed description of the disclosure categories, or for more information about ASCO s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: Lei Chen, Novartis (C); Min Amy Guo, Novartis (C); Hari Sharma, Analysis Group (C); Maryna Marynchenko, Analysis Group (C); Eric Q. Wu, Analysis Group (C) Consultant or Advisory Role: None Stock Ownership: Lei Chen, Novartis; Min Amy Guo, Novartis Honoraria: None Research Funding: Lizheng Shi, Novartis Expert Testimony: None Other Remuneration: None Author Contributions Conception and design: All authors Financial support: Lei Chen Collection and assembly of data: Lizheng Shi Data analysis and interpretation: All authors Manuscript writing: All authors Final approval of manuscript: All authors Corresponding author: Lizheng Shi, PhD, Regents Associate Professor, Tulane University, 1440 Canal St Suite 1900, New Orleans, LA 70112; lshi1@tulane.edu. Authors Disclosures of Potential Conflicts of Interest Although all authors completed the disclosure declaration, the following author(s) and/or an author s immediate family member(s) indicated a DOI: /JOP ; published online ahead of print at jop.ascopubs.org on May 28, References 1. Faderl S, Talpaz M, Estrov Z, et al: The biology of chronic myeloid leukemia. N Engl J Med 341: , Sawyers CL: Chronic myeloid leukemia. N Engl J Med 340: , Jemal A, Siegel R, Xu J, et al: Cancer statistics, CA Cancer J Clin 60: , Huang X, Cortes J, Kantarjian H: Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer 118: , Kantarjian H, Cortes J: Considerations in the management of patients with Philadelphia chromosome positive chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy. J Clin Oncol 29: , Talpaz M, Silver RT, Druker BJ, et al: Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: Results of a phase 2 study. Blood 99: , National Comprehensive Cancer Network: National Comprehensive Cancer Network clinical practice guidelines in oncology: Chronic myelogenous leukemia Druker BJ, Guilhot F, O Brien SG, et al: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355: , Hochhaus A, La Roseé P: Imatinib therapy in chronic myelogenous leukemia: Strategies to avoid and overcome resistance. Leukemia 18: , Jabbour E, Kantarjian HM, Jones D, et al: Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy. Blood 113: , Gorre ME, Mohammed M, Ellwood K, et al: Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: , Kantarjian HM, Shah NP, Cortes JE, et al: Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 119: , Kantarjian HM, Hochhaus A, Saglio G, et al: Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol 12: , Weisberg E, Manley PW, Cowan-Jacob SW, et al: Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 7: , Kantarjian H, Shah NP, Hochhaus A, et al: Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362: , Saglio G, Kim DW, Issaragrisil S, et al: Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362: , Kantarjian HM, Giles FJ, Bhalla KN, et al: Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood 117: , Stone R, Kantarjian H, Baccarani M, et al: Efficacy of dasatinib in patients with chronic-phase chronic myelogenous leukemia with resistance or intolerance to imatinib: 2-year follow-up data from START-C (CA ). Blood (ASH Annual Meeting Abstracts) 110, 2007 (abstr 734) 19. Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100: , de Lavallade H, Apperley JF, Khorashad JS, et al: Imatinib for newly diagnosed patients with chronic myeloid leukemia: Incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 26: , Steegman J, Michallet M, Morra E, et al: Imatinib use in chronic phase CML in clinical practice: The UNIC study. J Clin Oncol 26:15S, 2008 (suppl; abstr 7077) 6 JOURNAL OF ONCOLOGY PRACTICE

7 Imatinib Treatment in Ph CML 22. Hehlmann R, Lauseker M, Jung-Munkwitz S, et al: Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol 29: , Gambacorti-Passerini C, Antolini L, Mahon FX, et al: Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst 103: , Hochhaus A, O Brien SG, Guilhot F, et al: Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23: , Cortes J, O Brien S, Kantarjian H: Discontinuation of imatinib therapy after achieving a molecular response. Blood 104: , Mahon FX, Réa D, Guilhot J, et al: Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11: , Rousselot P, Huguet F, Rea D, et al: Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 109:58-60, Lucas CM, Wang L, Austin GM, et al: A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials. Leukemia 22: , Kantarjian H, Giles F, Wunderle L, et al: Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 354: , Talpaz M, Shah NP, Kantarjian H, et al: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354: , SEER statistics: Chronic myeloid leukemia, National Cancer Institute. seer.cancer.gov/statfacts/html/cmyl.html jop.ascopubs.org 7

8 Vander Velde et al Appendix Table A1. Patient Characteristics Patients with CML-CP (N 137) Characteristics No. % Age at first CML diagnosis, years Mean 64.8 SD 12.5 Race White Sex Male Primary insurance other than VA Medicare Preferred providers Other None Average follow-up duration, years Mean 4.0 SD 2.4 Year of CML diagnosis Abbreviations: CML, chronic myeloid leukemia; SD, standard deviation; VA, Veterans Affairs. Patients with at least one CML diagnosis between January 1, 2000, and June 30, 2011; the first diagnosis date is defined as the index date (N = 512) Patients 18 years as of the index date (n = 512) Patients in chronic phase of the disease as of the diagnosis (n = 323) Patients using imatinib treatment on or after the index date (n = 169) Patients using imatinib treatment on or after the index date as first-line therapy (n = 137) Figure A1. Sample counts. CML, chronic myeloid leukemia. 8 JOURNAL OF ONCOLOGY PRACTICE

9 Imatinib Treatment in Ph CML Survival Rate (%) By the end of Year 1 Year 2 survival 97.0% 90.5% Time Since Imatinib Initiation (days) Figure A2. Overall survival time, Kaplan-Meier analysis. 100 Survival Rate (%) By the end of Year 1 Year 2 Survival 78.3% 57.3% Figure A3. Survival time after disease progression, Kaplan-Meier analysis. Time Since Disease Progression Date (days) jop.ascopubs.org 9

CML Drugs and their Availability in the UK. Jane Apperley

CML Drugs and their Availability in the UK. Jane Apperley CML Drugs and their Availability in the UK Jane Apperley Drugs used in the treatment of CML Traditional chemotherapy Busulphan Hydoxycarbamide Interferon-alpha Omacetaxine Tyrosine kinase inhibitors Imatinib

More information

Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib

Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib Published Ahead of Print on September 12, 2014, as doi:10.3324/haematol.2013.085977. Copyright 2014 Ferrata Storti Foundation. Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and

More information

nilotinib 150mg hard capsules (Tasigna ) SMC No. (709/11) Novartis Pharmaceuticals UK Ltd

nilotinib 150mg hard capsules (Tasigna ) SMC No. (709/11) Novartis Pharmaceuticals UK Ltd nilotinib 150mg hard capsules (Tasigna ) SMC No. (709/11) Novartis Pharmaceuticals UK Ltd 08 July 2011 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product and advises

More information

A Time Line Of Chronic Myeloid Leukemia

A Time Line Of Chronic Myeloid Leukemia Chronic Myeloid Leukemia in 2011 An Update on Treatment and Monitoring Michael Deininger MD PhD Chief, Division of Hematology and Hematologic Malignancies M. M. Wintrobe Professor of Medicine A Time Line

More information

Initial choice of therapy among plenty for newly diagnosed chronic myeloid leukemia

Initial choice of therapy among plenty for newly diagnosed chronic myeloid leukemia CHRONIC MYELOID LEUKEMIA:THE PRISTINE PARADIGM FOR SUCCESSFUL TARGETED THERAPY Initial choice of therapy among plenty for newly diagnosed chronic myeloid leukemia David Marin 1 1 Hammersmith Hospital,

More information

treatments) worked by killing cancerous cells using chemo or radiotherapy. While these techniques can

treatments) worked by killing cancerous cells using chemo or radiotherapy. While these techniques can Shristi Pandey Genomics and Medicine Winter 2011 Prof. Doug Brutlag Chronic Myeloid Leukemia: A look into how genomics is changing the way we treat Cancer. Until the late 1990s, nearly all treatment methods

More information

CHRONIC MYELOGENOUS LEUKEMIA

CHRONIC MYELOGENOUS LEUKEMIA CHRONIC MYELOGENOUS LEUKEMIA Executive Summary We propose the inclusion of treatment options for chronic myelogenous leukemia (CML), in the category of anti-neoplastic agents, including imatinib, nilotinib,

More information

Previously Published Works UC Irvine

Previously Published Works UC Irvine Previously Published Works UC Irvine A University of California author or department has made this article openly available. Thanks to the Academic Senate s Open Access Policy, a great many UC-authored

More information

Creation of a Chronic Myeloid Leukemia Retrospective Outcomes Research Registry

Creation of a Chronic Myeloid Leukemia Retrospective Outcomes Research Registry Creation of a Chronic Myeloid Leukemia Retrospective Outcomes Research Registry David Stenehjem, Pharm.D. Research Assistant Professor Department of Pharmacotherapy Clinical Hematology/Oncology Pharmacist

More information

Recommendations for the Management of BCR-ABL-positive Chronic Myeloid Leukaemia. British Committee for Standards in Haematology.

Recommendations for the Management of BCR-ABL-positive Chronic Myeloid Leukaemia. British Committee for Standards in Haematology. Recommendations for the Management of BCR-ABL-positive Chronic Myeloid Leukaemia British Committee for Standards in Haematology. Author; Professor John Goldman Department of Haematology Imperial College

More information

Relative Risk (Sokal & Hasford): Relationship with Treatment Results. Michele Baccarani

Relative Risk (Sokal & Hasford): Relationship with Treatment Results. Michele Baccarani Relative Risk (Sokal & Hasford): Relationship with Treatment Results Michele Baccarani European LeukemiaNet EVOLVING CONCEPTS IN THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA VENICE 8 9 MAY 2006 Disease risk

More information

Cancer chemotherapy has long relied on generalized

Cancer chemotherapy has long relied on generalized n report n Value of Survival Gains in Chronic Myeloid Leukemia Wesley Yin, PhD; John R. Penrod, PhD; J. Ross Maclean, MD; Darius N. Lakdawalla, PhD; and Tomas Philipson, PhD Cancer chemotherapy has long

More information

NCCN Task Force Report: Tyrosine Kinase Inhibitor Therapy Selection in the Management of Patients With Chronic Myelogenous Leukemia

NCCN Task Force Report: Tyrosine Kinase Inhibitor Therapy Selection in the Management of Patients With Chronic Myelogenous Leukemia S-1 NCCN Task Force Report: Tyrosine Kinase Inhibitor Therapy Selection in the Management of Patients With Chronic Myelogenous Leukemia Susan O Brien, MD; Ellin Berman, MD; Joseph O. Moore, MD; Javier

More information

Response Definition, Evaluation and Monitoring. Michele Baccarani

Response Definition, Evaluation and Monitoring. Michele Baccarani Response Definition, Evaluation and Monitoring Michele Baccarani European LeukemiaNet EVOLVING CONCEPTS IN THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA VENICE 8 9 MAY 2006 Response definition, evaluation

More information

Treatment Recommendations for People Living with CML

Treatment Recommendations for People Living with CML Treatment Recommendations for People Living with CML Foreword by CML Workgroup Chronic myeloid leukaemia (CML) is a disease of the blood and bone marrow that results when there is a cancerous transformation

More information

CAS Chemistry Research Report Delivering the latest trends in global chemistry research

CAS Chemistry Research Report Delivering the latest trends in global chemistry research Delivering the latest trends in global chemistry research Human Genome Discoveries Spur Growth of Cancer Treatments www.cas.org Strength of the Human Genome Project and Targeted Drugs In, President Clinton

More information

in silico hematology

in silico hematology in silico hematology Application of mathematical modeling to predict the outcome of leukemia treatment by Ingmar Glauche and Ingo Röder Chronic Myeloid Leukemia (CML) accounts for about 20 % of all leukemias

More information

CML. cure. A Patient s Guide. Molecular Biology Diagnosis Stem Cell Transplant Monitoring New Drugs Questions to Ask and More

CML. cure. A Patient s Guide. Molecular Biology Diagnosis Stem Cell Transplant Monitoring New Drugs Questions to Ask and More A Patient s Guide to CML Molecular Biology Diagnosis Stem Cell Transplant Monitoring New Drugs Questions to Ask and More cure C a n c e r U p d at e s, R e s e a r c h & E d u c at i o n Based on science,

More information

Available online at www.jbr-pub.org. Open Access at PubMed Central. The Journal of Biomedical Research, 2014, 28(0):000-000.

Available online at www.jbr-pub.org. Open Access at PubMed Central. The Journal of Biomedical Research, 2014, 28(0):000-000. Available online at www.jbr-pub.org Open Access at PubMed Central The Journal of Biomedical Research, 2014, 28(0):000-000 Case Report The combination therapy of imatinib and dasatinib achieves longterm

More information

BRIEFING BOOK ONCOLOGY DRUGS ADVISORY COMMITTEE MEETING NDA 22-374. (omacetaxine mepesuccinate)

BRIEFING BOOK ONCOLOGY DRUGS ADVISORY COMMITTEE MEETING NDA 22-374. (omacetaxine mepesuccinate) BRIEFING BOOK ONCOLOGY DRUGS ADVISORY COMMITTEE MEETING NDA 22-374 OMAPRO (omacetaxine mepesuccinate) ChemGenex Pharmaceuticals, Inc. 3715 Haven Avenue, Suite 100 Menlo Park, CA 94025 AVAILABLE FOR PUBLIC

More information

PROGNOSIS IN ACUTE LYMPHOBLASTIC LEUKEMIA PROGNOSIS IN ACUTE MYELOID LEUKEMIA

PROGNOSIS IN ACUTE LYMPHOBLASTIC LEUKEMIA PROGNOSIS IN ACUTE MYELOID LEUKEMIA PROGNOSIS IN ACUTE LYMPHOBLASTIC LEUKEMIA UNFAVORABLE Advanced age High leukocyte count at diagnosis Presence of myeloid antigens Late achievement of CR Chromosomal abnormalities: t(9:22)(q34:q11) t(4;11)(q21;q23)

More information

Synopsis of Causation. Chronic Myeloid Leukaemia

Synopsis of Causation. Chronic Myeloid Leukaemia Ministry of Defence Synopsis of Causation Chronic Myeloid Leukaemia Author: Dr M A Vickers, University of Aberdeen, Aberdeen Validator: Professor John Goldman, Hammersmith Hospital, London September 2008

More information

La Targeted Therapy e l appropriatezza terapeutica

La Targeted Therapy e l appropriatezza terapeutica TRAINING REGIONALE PER FARMACISTI OSPEDALIERI SU LEUCEMIA MIELOIDE CRONICA (LMC), NUOVE TECNOLOGIE ED APPROCCI Roma, 16 Novembre 2015 La Targeted Therapy e l appropriatezza terapeutica Cinzia Dello Russo

More information

Health Insurance and Cancer Drug Reimbursement

Health Insurance and Cancer Drug Reimbursement Quality health plans & benefits Healthier living Financial well-being Intelligent solutions Health Insurance and Cancer Drug Reimbursement Michael Kolodziej, M.D., FACP National Medical Director, Oncology

More information

Improving Frontline Treatment for Chronic Myeloid Leukemia: Emerging Evidence for Use of Nilotinib and Dasatinib

Improving Frontline Treatment for Chronic Myeloid Leukemia: Emerging Evidence for Use of Nilotinib and Dasatinib Improving Frontline Treatment for Chronic Myeloid Leukemia: Emerging Evidence for Use of Nilotinib and Dasatinib Harry P. Erba, MD, PhD Dr. Erba is an Associate Professor in the Department of Internal

More information

Tutor Prof. Monica Bocchia Dissertation of Dr. Marzia Defina

Tutor Prof. Monica Bocchia Dissertation of Dr. Marzia Defina Doctorate in Genetics, Oncology and Clinical Medicine (GenOMeC) Allergology and clinical and experimental Immunology section XXV cicle Director: Prof. Alessandra Renieri Evaluation of residual CD34+Ph+

More information

Imatinib Mesylate in Chronic Myeloid Leukemia: A Prospective, Single Arm, Non-randomized Study

Imatinib Mesylate in Chronic Myeloid Leukemia: A Prospective, Single Arm, Non-randomized Study Original Article Imatinib Mesylate in Chronic Myeloid Leukemia: A Prospective, Single Arm, Non-randomized Study C Deshmukh*, T Saikia**, A Bakshi*, P Amare - Kadam***, C Baisane+, P Parikh++ Abstract Chronic

More information

I was just diagnosed, so my doctor and I are deciding on treatment. My doctor said there are several

I was just diagnosed, so my doctor and I are deciding on treatment. My doctor said there are several Track 3: Goals of therapy I was just diagnosed, so my doctor and I are deciding on treatment. My doctor said there are several factors she ll use to decide what s best for me. Let s talk about making treatment

More information

Protocol. Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia

Protocol. Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia Hematopoietic Stem Cell Transplantation for Chronic Myelogenous (80130) Medical Benefit Effective Date: 04/01/13 Next Review Date: 03/16 Preauthorization Yes Review Dates: 04/07, 05/08, 03/10, 03/11, 03/12,

More information

The Blood Cancer Twice As Likely To Affect African Americans: Multiple Myeloma

The Blood Cancer Twice As Likely To Affect African Americans: Multiple Myeloma The Blood Cancer Twice As Likely To Affect African Americans: Multiple Myeloma 11 th Annual National Leadership Summit on Health Disparities Innovation Towards Reducing Disparities Congressional Black

More information

Early mortality rate (EMR) in Acute Myeloid Leukemia (AML)

Early mortality rate (EMR) in Acute Myeloid Leukemia (AML) Early mortality rate (EMR) in Acute Myeloid Leukemia (AML) George Yaghmour, MD Hematology Oncology Fellow PGY5 UTHSC/West cancer Center, Memphis, TN May,1st,2015 Off-Label Use Disclosure(s) I do not intend

More information

Is the third-line chemotherapy feasible for non-small cell lung cancer? A retrospective study

Is the third-line chemotherapy feasible for non-small cell lung cancer? A retrospective study Turkish Journal of Cancer Volume 34, No.1, 2004 19 Is the third-line chemotherapy feasible for non-small cell lung cancer? A retrospective study MUSTAFA ÖZDO AN, MUSTAFA SAMUR, HAKAN BOZCUK, ERKAN ÇOBAN,

More information

Long Term Low Dose Maintenance Chemotherapy in the Treatment of Acute Myeloid Leukemia

Long Term Low Dose Maintenance Chemotherapy in the Treatment of Acute Myeloid Leukemia Long Term Low Dose Chemotherapy in the Treatment of Acute Myeloid Leukemia Murat TOMBULO LU*, Seçkin ÇA IRGAN* * Department of Hematology, Faculty of Medicine, Ege University, zmir, TURKEY ABSTRACT In

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: hematopoietic_stem-cell_transplantation_for_epithelial_ovarian_cancer 2/2001 11/2015 11/2016 11/2015 Description

More information

The CML Guide Information for Patients and Caregivers

The CML Guide Information for Patients and Caregivers The CML Guide Information for Patients and Caregivers LEUKEMIA LYMPHOMA CHRONIC MYELOGENOUS LEUKEMIA MYELOMA Printing of this publication made possible by a grant from A Message from John Walter President

More information

Introduction. About 10,500 new cases of acute myelogenous leukemia are diagnosed each

Introduction. About 10,500 new cases of acute myelogenous leukemia are diagnosed each Introduction 1.1 Introduction: About 10,500 new cases of acute myelogenous leukemia are diagnosed each year in the United States (Hope et al., 2003). Acute myelogenous leukemia has several names, including

More information

Treatment of Metastatic Non-Small Cell Lung Cancer: A Systematic Review of Comparative Effectiveness and Cost-Effectiveness

Treatment of Metastatic Non-Small Cell Lung Cancer: A Systematic Review of Comparative Effectiveness and Cost-Effectiveness Department of Veterans Affairs Health Services Research & Development Service Treatment of Metastatic Non-Small Cell Lung Cancer: A Systematic Review of Comparative Effectiveness and Cost-Effectiveness

More information

Stakeholder Insight: Acute Leukemias - Reaching the Limits of Cytotoxic Chemotherapy

Stakeholder Insight: Acute Leukemias - Reaching the Limits of Cytotoxic Chemotherapy Brochure More information from http://www.researchandmarkets.com/reports/1088137/ Stakeholder Insight: Acute Leukemias - Reaching the Limits of Cytotoxic Chemotherapy Description: The drug therapy of acute

More information

Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate

Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate Original Article Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate Joshi S, Sunita P, Deshmukh C, Gujral S, Amre P, Nair CN Department of Pathology,

More information

Update in Hematology Oncology Targeted Therapies. Mark Holguin

Update in Hematology Oncology Targeted Therapies. Mark Holguin Update in Hematology Oncology Targeted Therapies Mark Holguin 25 years ago Why I chose oncology People How to help people with possibly the most difficult thing they may have to deal with Science Turning

More information

Avastin in Metastatic Breast Cancer

Avastin in Metastatic Breast Cancer Non-interventional study Avastin in Metastatic Breast Cancer ML 21165 / 2007 Clinical Study Report Synopsis ROCHE ML21165 / WiSP Project RH09 / V. 1.0 / 24.06.2013 ROCHE ML21165-2 - Name of Sponsor Roche

More information

Imatinib blood level testing. A new initiative in the era of targeted therapy for Ph+ CML

Imatinib blood level testing. A new initiative in the era of targeted therapy for Ph+ CML Imatinib blood level testing A new initiative in the era of targeted therapy for Ph+ CML Imatinib (Gleevec /Glivec, formerly STI571) has sparked a revolution in cancer therapy by dramatically improving

More information

Big Data and Oncology Care Quality Improvement in the United States

Big Data and Oncology Care Quality Improvement in the United States Big Data and Oncology Care Quality Improvement in the United States Peter P. Yu, MD, FACP, FASCO President, American Society of Clinical Oncology Director of Cancer Research, Palo Alto Medical Foundation

More information

If several different trials are mentioned in one publication, the data of each should be extracted in a separate data extraction form.

If several different trials are mentioned in one publication, the data of each should be extracted in a separate data extraction form. General Remarks This template of a data extraction form is intended to help you to start developing your own data extraction form, it certainly has to be adapted to your specific question. Delete unnecessary

More information

DECISION AND SUMMARY OF RATIONALE

DECISION AND SUMMARY OF RATIONALE DECISION AND SUMMARY OF RATIONALE Indication under consideration Clinical evidence Clofarabine in the treatment of relapsed acute myeloid leukaemia (AML) The application was for clofarabine to remain in

More information

Methodological Challenges in Analyzing Patient-reported Outcomes

Methodological Challenges in Analyzing Patient-reported Outcomes Methodological Challenges in Analyzing Patient-reported Outcomes Elizabeth A. Hahn Center on Outcomes, Research and Education (CORE), Evanston Northwestern Healthcare, Evanston, IL Dept. of Preventive

More information

The CML Guide. Information for Patients and Caregivers. Chronic Myeloid Leukemia. Matthew, CML survivor. This publication was supported by

The CML Guide. Information for Patients and Caregivers. Chronic Myeloid Leukemia. Matthew, CML survivor. This publication was supported by The CML Guide Information for Patients and Caregivers Chronic Myeloid Leukemia Matthew, CML survivor This publication was supported by Revised 2014 A Message from Louis J. DeGennaro, PhD President and

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Cancer Drug and Biological Products Clinical Data in Marketing Applications U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and

More information

Chao-Sung Chang 1,2, Yi-Hsin Yang 3,4, Chien-Ning Hsu 5,6* and Min-Ting Lin 2

Chao-Sung Chang 1,2, Yi-Hsin Yang 3,4, Chien-Ning Hsu 5,6* and Min-Ting Lin 2 Chang et al. BMC Health Services Research 2012, 12:359 RESEARCH ARTICLE Open Access Trends in the treatment changes and medication persistence of chronic myeloid leukemia in Taiwan from 1997 to 2007: a

More information

Elderly males, especially white males, are the people at highest risk for suicide in America.

Elderly males, especially white males, are the people at highest risk for suicide in America. Statement of Ira R. Katz, MD, PhD Professor of Psychiatry Director, Section of Geriatric Psychiatry University of Pennsylvania Director, Mental Illness Research Education and Clinical Center Philadelphia

More information

Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns

Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns July 2013 Edition Vol. 7, Issue 7 Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns By Julie Katz, MPH, MPhil Biomarkers played a prominent role in the research presented in

More information

Stem Cell Transplantation

Stem Cell Transplantation Harmony Behavioral Health, Inc. Harmony Behavioral Health of Florida, Inc. Harmony Health Plan of Illinois, Inc. HealthEase of Florida, Inc. Ohana Health Plan, a plan offered by WellCare Health Insurance

More information

Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) Chronic Myelogenous Leukemia Version 3.2014 NCCN.org Continue Version 3.2014, 01/15/14 National Comprehensive Cancer Network, Inc. 2014,

More information

What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals

What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals What is New in Oncology Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals Personalized Medicine Personalized Genomics Genomic Medicine Precision Medicine Definition Application

More information

Chronic Myeloid Leukaemia: Molecular Abnormalities and Treatment Options

Chronic Myeloid Leukaemia: Molecular Abnormalities and Treatment Options Chronic Myeloid Leukaemia: Molecular Abnormalities and Treatment Options Niamh Appleby, Eimear Burke, Terry-Ann Curran and Elaine Neary, 4 th Year Medicine ABSTRACT Chronic myeloid leukaemia (CML) is a

More information

Cancer Treatments Subcommittee of PTAC Meeting held 18 September 2015. (minutes for web publishing)

Cancer Treatments Subcommittee of PTAC Meeting held 18 September 2015. (minutes for web publishing) Cancer Treatments Subcommittee of PTAC Meeting held 18 September 2015 (minutes for web publishing) Cancer Treatments Subcommittee minutes are published in accordance with the Terms of Reference for the

More information

Evaluation of Treatment Pathways in Oncology: An Example in mcrpc

Evaluation of Treatment Pathways in Oncology: An Example in mcrpc Evaluation of Treatment Pathways in Oncology: An Example in mcrpc Sonja Sorensen, MPH United BioSource Corporation Bethesda, MD 1 Objectives Illustrate selection of modeling approach for evaluating pathways

More information

Clinical trial enrollment among older cancer patients

Clinical trial enrollment among older cancer patients Clinical trial enrollment among older cancer patients Sharon H. Giordano MD, MPH Professor, Health Services Research Mariana Chavez Mac Gregor MD, MSc Assistant Professor, Breast Medical Oncology Department

More information

NATIONAL CANCER DRUG FUND PRIORITISATION SCORES

NATIONAL CANCER DRUG FUND PRIORITISATION SCORES NATIONAL CANCER DRUG FUND PRIORITISATION SCORES Drug Indication Regimen (where appropriate) BORTEZOMIB In combination with dexamethasone (VD), or with dexamethasone and thalidomide (VTD), is indicated

More information

Molecular Biology: Measuring and Reporting BCR-ABL Transcripts Level. Giuseppe Saglio

Molecular Biology: Measuring and Reporting BCR-ABL Transcripts Level. Giuseppe Saglio Molecular Biology: Measuring and Reporting BCR-ABL Transcripts Level Giuseppe Saglio 1 st Question to be addressed Why is it so important to measure BCR- ABL transcript levels in the follow-up of CML patients

More information

Targeting Cancer: Innovation in the Treatment of Chronic Myelogenous Leukemia EXECUTIVE SUMMARY. New England Healthcare Institute

Targeting Cancer: Innovation in the Treatment of Chronic Myelogenous Leukemia EXECUTIVE SUMMARY. New England Healthcare Institute Targeting Cancer: Innovation in the Treatment of Chronic Myelogenous Leukemia New England Healthcare Institute NEHI Innovation Series March 2004 Executive Summary From drugs and medical devices, to information

More information

Not All Clinical Trials Are Created Equal Understanding the Different Phases

Not All Clinical Trials Are Created Equal Understanding the Different Phases Not All Clinical Trials Are Created Equal Understanding the Different Phases This chapter will help you understand the differences between the various clinical trial phases and how these differences impact

More information

Hodgkin Lymphoma Disease Specific Biology and Treatment Options. John Kuruvilla

Hodgkin Lymphoma Disease Specific Biology and Treatment Options. John Kuruvilla Hodgkin Lymphoma Disease Specific Biology and Treatment Options John Kuruvilla My Disclaimer This is where I work Objectives Pathobiology what makes HL different Diagnosis Staging Treatment Philosophy

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for CLL and SLL File Name: Origination: Last CAP Review: Next CAP Review: Last Review: hematopoietic_stem-cell_transplantation_for_cll_and_sll

More information

Everolimus plus exemestane for second-line endocrine treatment of oestrogen receptor positive metastatic breast cancer

Everolimus plus exemestane for second-line endocrine treatment of oestrogen receptor positive metastatic breast cancer LONDON CANCER NEWS DRUGS GROUP RAPID REVIEW Everolimus plus exemestane for second-line endocrine treatment of oestrogen receptor positive metastatic breast cancer Everolimus plus exemestane for second-line

More information

Treatment of Low Risk MDS. Overview. Myelodysplastic Syndromes (MDS)

Treatment of Low Risk MDS. Overview. Myelodysplastic Syndromes (MDS) Overview Amy Davidoff, Ph.D., M.S. Associate Professor Pharmaceutical Health Services Research Department, Peter Lamy Center on Drug Therapy and Aging University of Maryland School of Pharmacy Clinical

More information

Type of intervention Treatment. Economic study type Cost-effectiveness analysis.

Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Impact of uncertainty on cost-effectiveness analysis of medical strategies: the case of highdose chemotherapy for breast cancer patients Marino P, Siani C, Roche H, Moatti J P Record Status This is a critical

More information

Pharmacogenomic markers in EGFR-targeted therapy of lung cancer

Pharmacogenomic markers in EGFR-targeted therapy of lung cancer Pharmacogenomic markers in EGFR-targeted therapy of lung cancer Rafal Dziadziuszko, MD, PhD University of Colorado Cancer Center, Aurora, CO, USA Medical University of Gdansk, Poland EMEA Workshop on Biomarkers,

More information

Cytogenetics for the Rest of Us: A Primer

Cytogenetics for the Rest of Us: A Primer Cytogenetics for the Rest of Us: A Primer James J. Stark, MD, FACP Medical Director Cancer Program Maryview Medical Center Diane Maia, M.D. Pathologist, Bon Secours Hampton Roads Case #1 78 y.o. lady seen

More information

Estimated New Cases of Leukemia, Lymphoma, Myeloma 2014

Estimated New Cases of Leukemia, Lymphoma, Myeloma 2014 ABOUT BLOOD CANCERS Leukemia, Hodgkin lymphoma (HL), non-hodgkin lymphoma (NHL), myeloma, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) are types of cancer that can affect the

More information

Introduction of a Standard Drug Formulary in Hospital Authority

Introduction of a Standard Drug Formulary in Hospital Authority Introduction of a Standard Drug Formulary in Hospital Authority PURPOSE This paper seeks Members views on the introduction of a Standard Hospital Authority Drug Formulary ( ) ( Standard Drug Formulary

More information

Answering your questions on Chronic Myeloid Leukaemia (CML)

Answering your questions on Chronic Myeloid Leukaemia (CML) Answering your questions on Chronic Myeloid Leukaemia (CML) Your guide to understanding CML and Glivec (imatinib) treatment The information in this booklet is designed to help you understand chronic myeloid

More information

Community Center Readiness Guide Additional Resource #17 Protocol for Physician Assistants and Advanced Practice Nurses

Community Center Readiness Guide Additional Resource #17 Protocol for Physician Assistants and Advanced Practice Nurses Community Center Readiness Guide Additional Resource #17 Protocol for Physician Assistants and Advanced Practice Nurses PROTOCOL FOR PHYSICIAN ASSISTANTS AND ADVANCED PRACTICE NURSES 1. POLICY Advanced

More information

REFERENCE CODE GDHC212DFR PUBLICAT ION DATE JUNE 2013 GSK1572932A (NON-SMALL CELL LUNG CANCER) FORECAST AND MARKET ANALYSIS TO 2022

REFERENCE CODE GDHC212DFR PUBLICAT ION DATE JUNE 2013 GSK1572932A (NON-SMALL CELL LUNG CANCER) FORECAST AND MARKET ANALYSIS TO 2022 REFERENCE CODE GDHC212DFR PUBLICAT ION DATE JUNE 2013 GSK1572932A (NON-SMALL CELL LUNG CANCER) GSK1572932A (NON-SMALL CELL LUNG CANCER) - Executive Summary GSK1572932A (MAGE-A3): Key Metrics in NSCLC Markets

More information

Stem Cell Transplantation for Acute Lymphoblastic Leukemia

Stem Cell Transplantation for Acute Lymphoblastic Leukemia Stem Cell Transplantation for Acute Lymphoblastic Leukemia Mona Shafey MD, FRCPC Bone Marrow Transplant Fellow Alberta Blood and Marrow Transplant Program 1 of 14 Stem Cell Transplantation for Acute Lymphoblastic

More information

Chronic myeloid leukemia (CML) is one of the most extensively. Current and Emerging Treatment Options in Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is one of the most extensively. Current and Emerging Treatment Options in Chronic Myeloid Leukemia 2171 Current and Emerging Treatment Options in Chronic Myeloid Leukemia Elias Jabbour, MD Jorge E. Cortes, MD Francis J. Giles, MD Susan O Brien, MD Hagop M. Kantarjian, MD Department of Leukemia, The

More information

What is chronic myeloid leukaemia?

What is chronic myeloid leukaemia? Chronic Myeloid Leukaemia What is chronic myeloid leukaemia? Let us explain it to you. www.anticancerfund.org www.esmo.org ESMO/ACF Patient Guide Series based on the ESMO Clinical Practice Guidelines CHRONIC

More information

MEDICAL COVERAGE POLICY

MEDICAL COVERAGE POLICY Important note Even though this policy may indicate that a particular service or supply is considered covered, this conclusion is not necessarily based upon the terms of your particular benefit plan. Each

More information

Is going for cure in chronic myeloid leukemia possible and justifiable?

Is going for cure in chronic myeloid leukemia possible and justifiable? CHRONIC MYELOID LEUKEMIA:THE PRISTINE PARADIGM FOR SUCCESSFUL TARGETED THERAPY Is going for cure in chronic myeloid leukemia possible and justifiable? François-Xavier Mahon 1,2 1 Laboratoire d Hématologie,

More information

The Treatment of Leukemia

The Treatment of Leukemia The Treatment of Leukemia Guest Expert: Peter, MD Associate Professor of Hematology Director, Yale Cancer Center Leukemia Program www.wnpr.org www.yalecancercenter.org Hi, I am Bruce Barber and welcome

More information

Prior Authorization Guideline

Prior Authorization Guideline Prior Authorization Guideline Guideline: PS Inj - Alimta Therapeutic Class: Antineoplastic Agents Therapeutic Sub-Class: Antifolates Client: PS Inj Approval Date: 8/2/2004 Revision Date: 12/5/2006 I. BENEFIT

More information

A Career in Pediatric Hematology-Oncology? Think About It...

A Career in Pediatric Hematology-Oncology? Think About It... A Career in Pediatric Hematology-Oncology? Think About It... What does a pediatric hematologist-oncologist do? What kind of training is necessary? Is there a future need for specialists in this area? T

More information

Cytogenetic Profile of Variant Philadelphia Translocations in Chronic Myeloid Leukemia

Cytogenetic Profile of Variant Philadelphia Translocations in Chronic Myeloid Leukemia International Journal of Scientific and Research Publications, Volume 4, Issue 12, December 2014 1 Cytogenetic Profile of Variant Philadelphia Translocations in Chronic Myeloid Leukemia Chin Yuet Meng,

More information

OCT-1, ABCB1, and ABCG2 Expression in Imatinib-Resistant Chronic Myeloid Leukemia Treated with Dasatinib or Nilotinib

OCT-1, ABCB1, and ABCG2 Expression in Imatinib-Resistant Chronic Myeloid Leukemia Treated with Dasatinib or Nilotinib Original Article www.cmj.ac.kr,, and Expression in Imatinib-Resistant Chronic Myeloid Leukemia Treated with Dasatinib or Nilotinib Yeo-Kyeoung Kim 1, *, Seung-Shin Lee 1, Sung-Hoon Jeong 1, Jae-Sook Ahn

More information

Verso un interruzione dei farmaci nella leucemia mieloide cronica

Verso un interruzione dei farmaci nella leucemia mieloide cronica Verso un interruzione dei farmaci nella leucemia mieloide cronica Giuseppe Saglio Rational to try to discontinue therapy Quality of life Long-term side effects of therapy still unknown Cost Terms and definitions

More information

Treating Chronic Myeloid Leukemia: Improving Management Through Understanding of the Patient Experience

Treating Chronic Myeloid Leukemia: Improving Management Through Understanding of the Patient Experience Oncology Nursing Society. Unauthorized reproduction, in part or in whole, is strictly prohibited. For permission to photocopy, post online, reprint, adapt, or otherwise reuse any or all content from this

More information

Robert Okwemba, BSPHS, Pharm.D. 2015 Philadelphia College of Pharmacy

Robert Okwemba, BSPHS, Pharm.D. 2015 Philadelphia College of Pharmacy Robert Okwemba, BSPHS, Pharm.D. 2015 Philadelphia College of Pharmacy Judith Long, MD,RWJCS Perelman School of Medicine Philadelphia Veteran Affairs Medical Center Background Objective Overview Methods

More information

Guidance for Industry FDA Approval of New Cancer Treatment Uses for Marketed Drug and Biological Products

Guidance for Industry FDA Approval of New Cancer Treatment Uses for Marketed Drug and Biological Products Guidance for Industry FDA Approval of New Cancer Treatment Uses for Marketed Drug and Biological Products U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation

More information

Breast cancer treatment for elderly women: a systematic review

Breast cancer treatment for elderly women: a systematic review Breast cancer treatment for elderly women: a systematic review Gerlinde Pilkington Rumona Dickson Anna Sanniti Funded by the NCEI and POI Elderly people less likely to receive chemotherapy than younger

More information

2. Background This was the fourth submission for everolimus requesting listing for clear cell renal carcinoma.

2. Background This was the fourth submission for everolimus requesting listing for clear cell renal carcinoma. PUBLIC SUMMARY DOCUMENT Product: Everolimus, tablets, 5 mg and 10 mg, Afinitor Sponsor: Novartis Pharmaceuticals Australia Pty Ltd Date of PBAC Consideration: November 2011 1. Purpose of Application To

More information

Hematologic Malignancies Chronic Myeloid Leukemia

Hematologic Malignancies Chronic Myeloid Leukemia Chronic Myeloid Leukemia What Else is there Beyond Protein Kinase Inhibitors? Elias Jabbour, MD Associate Professor, Leukemia Department, MD Anderson Cancer Center, Houston, Texas, US Abstract Chronic

More information

Department of Veterans Affairs Health Services Research and Development - A Systematic Review

Department of Veterans Affairs Health Services Research and Development - A Systematic Review Department of Veterans Affairs Health Services Research & Development Service Effects of Health Plan-Sponsored Fitness Center Benefits on Physical Activity, Health Outcomes, and Health Care Costs and Utilization:

More information

Chronic myeloid leukemia in Asia

Chronic myeloid leukemia in Asia Int J Hematol (2009) 89:14 23 DOI 10.1007/s12185-008-0230-0 REVIEW ARTICLE Chronic myeloid leukemia in Asia Wing Y. Au Æ Priscilla B. Caguioa Æ Charles Chuah Æ Szu Chun Hsu Æ Saengsuree Jootar Æ Dong-Wook

More information

AML: How to characterize and treat elderly patients non fit for standard chemotherapy

AML: How to characterize and treat elderly patients non fit for standard chemotherapy m1 AML: How to characterize and treat elderly patients non fit for standard chemotherapy Clinic for Medicine III University Hospital Munich Campus Grosshadern AMLCG study group Karsten Spiekermann, MD

More information

pan-canadian Oncology Drug Review Final Economic Guidance Report Lenalidomide (Revlimid) for Multiple Myeloma October 22, 2013

pan-canadian Oncology Drug Review Final Economic Guidance Report Lenalidomide (Revlimid) for Multiple Myeloma October 22, 2013 pan-canadian Oncology Drug Review Final Economic Guidance Report Lenalidomide (Revlimid) for Multiple Myeloma October 22, 2013 DISCLAIMER Not a Substitute for Professional Advice This report is primarily

More information

Shaji Kumar, M.D. Multiple Myeloma: Multiple myeloma (MM) is the second most common hematological

Shaji Kumar, M.D. Multiple Myeloma: Multiple myeloma (MM) is the second most common hematological An update on the management of multiple myeloma and amyloidosis Shaji Kumar, M.D. Multiple Myeloma: Multiple myeloma (MM) is the second most common hematological malignancy in this country affecting nearly

More information

GUIDELINES ADJUVANT SYSTEMIC BREAST CANCER

GUIDELINES ADJUVANT SYSTEMIC BREAST CANCER GUIDELINES ADJUVANT SYSTEMIC BREAST CANCER Author: Dr Susan O Reilly On behalf of the Breast CNG Written: December 2008 Agreed at CNG: June 2009 & June 2010 Review due: June 2011 Guidelines Adjuvant Systemic

More information

Prior Authorization, Pharmacy and Health Case Management Information. Prior Authorization. Pharmacy Information. Health Case Management

Prior Authorization, Pharmacy and Health Case Management Information. Prior Authorization. Pharmacy Information. Health Case Management Prior Authorization, Pharmacy and Health Case Management Information The purpose of this information sheet is to provide you with details on how Great-West Life will be assessing and managing your claim

More information

Low dose capecitabine is effective and relatively nontoxic in breast cancer treatment.

Low dose capecitabine is effective and relatively nontoxic in breast cancer treatment. 1 Low dose capecitabine is effective and relatively nontoxic in breast cancer treatment. John T. Carpenter, M.D. University of Alabama at Birmingham NP 2508 1720 Second Avenue South Birmingham, AL 35294-3300

More information

National Horizon Scanning Centre. Vandetanib (Zactima) for advanced or metastatic non-small cell lung cancer. December 2007

National Horizon Scanning Centre. Vandetanib (Zactima) for advanced or metastatic non-small cell lung cancer. December 2007 Vandetanib (Zactima) for advanced or metastatic non-small cell lung cancer December 2007 This technology summary is based on information available at the time of research and a limited literature search.

More information