Age Disparity in the Dissemination of Imatinib Mesylate (Gleevec) for Treating Chronic Myeloid Leukemia

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Age Disparity in the Dissemination of Imatinib Mesylate (Gleevec) for Treating Chronic Myeloid Leukemia Chuck Wiggins, Ph.D. Director and Principal Investigator New Mexico Tumor Registry North American Association of Central Cancer Registries June 23, 2011 University of New Mexico Health Sciences Center

Collaborators Linda C. Harlan, Ph.D. National Cancer Institute Harold E. Nelson, M.A. New Mexico Tumor Registry Jennifer Stevens, B.A. IMS, Incorporated Cheryl L. Willman, M.D. University of New Mexico Edward N. Libby, M.D. University of New Mexico Robert A. Hromas, M.D. University of New Mexico Funding National Cancer Institute Leukemia and Lymphoma Society

Chronic Myeloid Leukemia Myeloproliferative disorder Philadelphia chromosome Course of disease: Chronic phase Accelerated phase Blast phase Annual number of new cases: United States 4,830 Annual number of deaths: United States 450

1960 Identification of the Philadelphia Chromosome Peter Nowell University of Pennsylvania School of Medicine David Hungerford Fox Chase Cancer Center

1972 Philadelphia Chromosome results from translocation Janet Rowley University of Chicago t(9,22;q34,q11)

1982 Abl gene translocated from 9q to 22q Annelies de Klein and colleagues Erasmus University

Protein Tyrosine Kinases Enzymes agents of change Modulate a number of cellular events: Differentiation Growth Metabolism Apoptosis

The BCR ABL gene produces an abnormal tyrosine kinase protein that results in the disordered myelopoiesis found in Chronic Myeloid Leukemia

Imatinib Mesylate (Gleevec TM, Novartis, Basel, Switzerland) Tyrosine Kinase Inhibitor FDA approved in May, 2001 Highly active against Chronic Myeloid Leukemia and Gastro Intestinal Stromal Tumors (GIST)

Late 1990 s to Mid 2000 s: Clinical Trials for Imatinib Brian Druker

Data Sources 1. SEER Program Patterns of Care Study, 2003 2. Survival data from SEER Program, 1990 2004 3. Mortality rates based on death certificates from the National Center for Health Statistics, 1990 2004

Study Objectives 1. Characterize dissemination of imatinib mesylate therapy for chronic myeloid leukemia in the general population 2. Determine if administration of imatinib mesylate therapy influenced survival rates for chronic myeloid leukemia in the general population 3. Determine if administration of imatinib mesylate therapy influenced mortality rates for chronic myeloid leukemia in the general population

SEER Program Patterns of Care Studies Overview Conducted annually since 1987 Document trends in cancer related care, with emphasis on diagnosis and treatment Targets 3 4 cancer sites/types each year Methods Detailed re abstract of medical records Brief questionnaire sent to physicians

SEER Program Patterns of Care Study 2003 Target Cancers Chronic Myeloid Leukemia Multiple Myeloma Bladder B Cell Lymphoma Focus on Chronic Myeloid Leukemia Documented use of imatinib mesylate n=403

Percentage of Chronic Myeloid Leukemia cases treated with imatinib, by race/ethnicity 100 90 80 70 60 50 40 30 20 10 0 Non Hispanic White Black Hispanic Other

Percentage of Chronic Myeloid Leukemia cases treated with imatinib, by quartile of median family income 100 90 80 70 60 50 40 30 20 10 0 Q 1 Q 2 Q 3 Q 4

Percentage of Chronic Myeloid Leukemia cases treated with imatinib, by age at diagnosis 100 90 80 70 60 50 40 30 20 10 0 20 29 30 39 40 49 50 59 60 69 70 79 80+

Patterns of Care Study Participants: 20 59 years of age at diagnosis Survival (months) by imatinib status (yes/no)

Patterns of Care Study Participants: 60 79 years of age at diagnosis Survival (months) by imatinib status (yes/no)

Patterns of Care Study Participants: 80+ years of age at diagnosis Survival (months) by imatinib status (yes/no)

Population Based Survival SEER Program Chronic Myeloid Leukemia cases newly diagnosed 1990 2004 1990 1997 Pre Imatinib 1998 2000 Peri Imatinib 2001 2004 Post Imatinib Percent surviving by month up to 36 months following CML diagnosis Survival function from Cox model

Chronic Myeloid Leukemia: 20 59 years of age at diagnosis Survival (months) by time period of diagnosis

Chronic Myeloid Leukemia: 60 79 years of age at diagnosis Survival (months) by time period of diagnosis

Chronic Myeloid Leukemia: 80+ years of age at diagnosis Survival (months) by time period of diagnosis

Population Based Mortality Rates National Center for Health Statistics Death certificates from all 50 United States Chronic Myeloid Leukemia deaths, 1990 2004 Age specific mortality rates

1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 10.00 1.00 0.10 Chronic Myeloid Leukemia Age specific mortality rates, 1975 2004 by age at death 80+ years 60-79 years 20-59 years Year of Death Annual Percent Change (Final Period) -7.8-11.9-17.6 Mortality Rate per 100,000

Summary Imatinib mesylate was widely disseminated for the treatment of chronic myeloid leukemia in 2003 The percentage of patients with chronic myeloid leukemia who received imatinib mesylate decreased with age Administration of imatinib mesylate did not vary by sex, race/ethnicity, socioeconomic status, or place of residence (i.e., urban vs. rural residence) Widespread dissemination of imatinib mesylate improved survival from chronic myeloid leukemia in the general population; least beneficial for elderly Dissemination of imatinib mesylate resulted in an overall decrease in mortality rates for chronic myeloid leukemia; least beneficial for elderly

Chuck Wiggins New Mexico Tumor Registry MSC 11 6020 1 University of New Mexico Albuquerque, New Mexico 87131 (505) 272-3127 cwiggins@salud.unm.edu http://hsc.unm.edu/som/nmtr