Use and Patterns of Supportive Care Among Patients Receiving Myelosuppressive Chemotherapy for Breast Cancer, Colorectal Cancer, Lung Cancer, or Non-Hodgkin's Lymphoma in US Clinical Practice

Abstract Background: Supportive care with colony-stimulating factors (CSFs) and antimicrobials (AMBs) is recommended for many patients receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin's lymphoma (NHL). However, evidence on the use and patterns of pharmacotherapy given to prevent, control, or relieve complications and side effects (such as febrile neutropenia [FN]), and to improve patient comfort and quality of life, among this patient population in US clinical practice is limited. Method s: A retrospective cohort design and data from four US health systems-Geisinger Health System, Henry Ford Health System, Kaiser Permanente Northwest, and Reliant Medical Group-spanning 2009-2013 were employed. The study population comprised all patients who received myelosuppressive chemotherapy for invasive breast cancer, invasive colorectal cancer, invasive lung cancer, or NHL. Data were collected via a standardized case report form (CRF) using electronic medical records systems, administrative data warehouses, medical charts, and cancer registries, and included patient demographics and clinical profile, cancer, treatment, and outcomes. For each subject, the first qualifying chemotherapy course, and each cycle and each FN episode within the course, was identified. Supportive care included prophylactic use of CSF agents (i.e., filgrastim, tbo-filgrastim, pegfilgrastim, and sargramostim) and AMBs (including antibiotics, antifungals, and antivirals), and were characterized on a cycle-specific basis in terms of agent received, dose, route of administration, timing, and duration of administration, as appropriate. Analyses described herein were descriptive in nature, and were based on an interim dataset. Results: The study population included a total of 527 patients who received myelosuppressive chemotherapy for breast cancer (n=281), colorectal cancer (n=95), lung cancer (n=95), or NHL (n=56) (Table). Among all subjects, mean (SD) age was 60 (13) years (40% aged ≥65 years), 17% had cardiovascular disease, 16% had lung disease, and 11% had diabetes; 33% of all patients had metastatic disease (7% of these patients had metastasis to bone), and 36% had previously received myelosuppressive therapy. Forty-two percent of all patients received CSF prophylaxis in cycle 1, and 55% received CSF prophylaxis in ≥1 cycles during their course; the mean number of CSF prophylaxis cycles, among those receiving these agents, was 3.9 (mean number of cycles in total, 7.1). Most patients received prophylaxis with pegfilgrastim (66%), and the remainder with filgrastim (34%). AMB prophylaxis was administered to 5% of patients in cycle 1 and 10% of patients at any time during their course. FN incidence proportion during the chemotherapy course was 14.2%, and was highest in cycle 1 (6.6%). Conclusion: In this retrospective evaluation of patients receiving myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or NHL, less than one-half of all patients (on average) received supportive care with CSF or AMB prophylaxis beginning in cycle 1 and few additional patients received CSF/AMB prophylaxis in subsequent cycles. FN was not uncommon, especially in the first cycle. Careful consideration should be given to identifying patients within this population who are at elevated risk of FN to ensure appropriate use of supportive care. Disclosures Weycker: Amgen, Inc.: Research Funding. Silvia:Amgen, Inc.: Research Funding. Richert-Boe:Amgen, Inc.: Research Funding. Bensink:Amgen, Inc.: Employment, Equity Ownership. Brady:Amgen, Inc.: Research Funding. Lamerato:Amgen, Inc.: Research Funding. Lipkovich:Amgen, Inc.: Research Funding. Siddiqui:Amgen, Inc.: Research Funding. Chandler:Amgen, Inc.: Employment, Equity Ownership.

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Use of Chemotherapy and Same-Day Pegfilgrastim Prophylaxis in US Clinical Practice

Blood ◽

10.1182/blood.v124.21.4825.4825 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4825-4825 ◽

Cited By ~ 5

Author(s):

Derek Weycker ◽

Hongsheng Wu ◽

May Hagiwara ◽

Xiaoyan Li ◽

Richard L Barron

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Lung Cancer ◽

Clinical Practice ◽

Research Funding ◽

Cancer Colorectal ◽

Tumor Type ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Equity Ownership

Abstract Background: Primary prophylaxis with pegfilgrastim has been shown to reduce the risk of febrile neutropenia, a life-threatening consequence of myelosuppressive chemotherapy. Pegfilgrastim is not indicated for administration during the interval between 14 days before and 24 hours after cytotoxic chemotherapy because pegfilgrastim induces proliferation of myeloid progenitor cells, and these proliferating cells may be especially sensitive to myelotoxic agents. A randomized, double-blind, phase 2 study (Burris 2010) and observational studies (Skarlos 2009, Cheng 2014) have reported poorer outcomes with same-day pegfilgrastim administration compared to next-day administration. Nonetheless, some healthcare providers administer pegfilgrastim to their patients on the same day as chemotherapy rather than requiring the patients to return for an injection the next day. This is the first large-scale analysis of same-day pegfilgrastim use in US clinical practice. Methods: In this retrospective cohort study, we examined the day of administration of pegfilgrastim prophylaxis relative to the completion of chemotherapy in adults with solid tumors (eg, breast cancer, colorectal cancer, and lung cancer) and non-Hodgkin’s lymphoma (NHL) treated in the outpatient setting. Data spanning 2003–2011 were obtained from 2 large private US healthcare claims databases—the Truven Health Analytics MarketScan® Database and the IMS Health PharMetrics Plus™ Database—and were pooled for analysis. Only patients who received triweekly (Q3W) or monthly (Q4W) chemotherapy regimens were included. For each patient, only the first documented chemotherapy course was included, and in the first course, only cycles with medical claims for pegfilgrastim prophylaxis were included. Administration of pegfilgrastim prophylaxis was classified as day 0 (same day), day 1, days 2-3, or days 4-5 relative to the last day of administration of myelosuppressive chemotherapy in the cycle. Analyses were conducted on an overall basis as well as by tumor type and chemotherapy regimen. Results: We identified 69,509 patients who received pegfilgrastim prophylaxis in 244,687 chemotherapy cycles. We found that pegfilgrastim was administered on the same day as chemotherapy in 13.4% of first cycles and 13.0% of subsequent cycles. Table 1 shows patient characteristics for 4 of the most common tumor types. Table 2 shows the day of pegfilgrastim administration. Conclusion: This large retrospective study provides data on the prevalence of same-day pegfilgrastim administration in US clinical practice. Despite dosing guidance on the pegfilgrastim label and prior research, an important minority of patients are receiving same-day prophylaxis. A future study will evaluate clinical outcomes in this study population. Table 1 Breast Cancer Colorectal Cancer Lung Cancer NHL No. of patients 33,076 1,251 12,888 10,433 Age, mean (SD), years 54.8 (10.3) 60.1 (11.3) 64.6 (9.9) 62.9 (13.7) Age < 65, % 84.7 68.5 53.3 56.5 Age ≥ 65, % 15.3 31.5 46.7 43.5 Male, % 0.0 42.9 54.2 54.2 Most common regimen, (%) AC/AC-T (27.4) FOLFOX (42.4) Carboplatin + paclitaxel (22.8) CHOP-R (62.1) Abstract 4825. Table 2 Cycle 1 Cycles 2+ Day of Administration of Pegfilgrastim Prophylaxis*, % Day of Administration of Pegfilgrastim Prophylaxis*, % No. of Cycles Same Day Day 1 Days 2-3 Days 4-5 No. of Cycles Same Day Day 1 Days 2-3 Days 4-5 All cancer 49,028 13.4 68.5 16.3 1.8 195,659 13.0 69.8 15.7 1.5 Breast cancer 24,074 12.5 74.1 12.6 0.9 98,955 12.1 75.4 11.6 1.0 AC/AC-T 5,260 16.1 70.1 12.9 0.8 27,563 13.9 72.9 12.1 1.1 Colorectal cancer 563 19.7 22.4 43.2 14.7 3,920 8.1 19.1 66.9 6.0 FOLFOX 163 11.0 16.0 69.9 3.1 2,127 5.3 17.1 74.0 3.7 Lung cancer 9,184 11.7 62.4 24.5 1.4 29,434 11.9 61.3 25.5 1.4 Carboplatin + paclitaxel 2,223 11.1 72.7 15.1 1.1 5,977 12.0 74.1 13.1 0.9 NHL 7,814 13.0 70.4 15.6 1.0 30,067 12.4 73.1 13.5 1.0 CHOP-R 4,891 12.2 73.0 14.0 0.8 20,905 11.7 75.7 11.9 0.8 *Relative to last day of administration of myelosuppressive chemotherapy Disclosures Weycker: Amgen Inc.: Research Funding. Wu:Amgen Inc.: Research Funding. Hagiwara:Amgen Inc.: Research Funding. Li:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership.

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Predictors of Febrile Neutropenia Among Cancer Patients Receiving Myelosuppressive Chemotherapy in US Clinical Practice

Blood ◽

10.1182/blood-2019-123524 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5854-5854

Author(s):

Gary H. Lyman ◽

Kathryn Richert-Boe ◽

Lois Lamerato ◽

Manpreet Kaur ◽

Neel Shah ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Risk Factors ◽

Lung Cancer ◽

Research Funding ◽

Risk Level ◽

Myelosuppressive Chemotherapy ◽

Study Population ◽

Equity Ownership ◽

Chemotherapy Initiation

Introduction: Febrile neutropenia (FN) is a common and serious complication of myelosuppressive chemotherapy. Assessment of FN risk has typically focused on the chemotherapy course or the first cycle of chemotherapy, and risk factors present at the time of chemotherapy initiation. However, a substantial proportion of FN episodes occur after the first chemotherapy cycle, and it is likely that the risk of these episodes is determined-at least in part-by events/care occurring during the course of chemotherapy (e.g., prior FN, chemotherapy dose reductions, colony-stimulating factor [CSF] prophylaxis). The objectives of this study were two-fold: (1) to evaluate FN risk factors that are ascertained at chemotherapy initiation as well as those ascertained on a cycle-specific basis during the chemotherapy course; and (2) to evaluate how use of CSF prophylaxis may reduce this risk. Methods: A retrospective cohort design and data from four US health systems-Henry Ford Health System, Kaiser Permanente Northwest, Reliant Medical Group, and Geisinger Health System-were employed. Data included patients' demographics and clinical profile, cancer, treatment, and outcomes, and were compiled from electronic medical records systems, administrative data warehouses, medical charts, and cancer registries. The study population comprised all patients who received a course of myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or non-Hodgkin's lymphoma (NHL) from 2009-2017. For each patient, each cycle of chemotherapy during the course was characterized and included as a separate observation in the analytic file; thus, each patient could contribute multiple chemotherapy cycles to the analysis. Candidate predictors were identified from national guidelines and published literature; cycle number, FN events occurring prior to the cycle of interest, chemotherapy relative dose intensity (RDI), and CSF prophylaxis were defined on a cycle-specific basis. Independent risk factors for FN were evaluated within a multivariable framework using generalized estimating equations with a logistic link function. Results: The study population included 4091 patients who received myelosuppressive chemotherapy for breast cancer (49%), colorectal cancer (17%), lung cancer (23%), or NHL (11%), and who contributed 29,964 cycles of observation; mean age was 61 years, 36% had metastatic disease, 36% received CSF prophylaxis in cycle 1, and 46% received prophylaxis in ≥1 cycle. During the course, 13.8% of patients developed FN; risk was greatest in cycle 1 (5.2%). Independent predictors of FN included patient, cancer, and chemotherapy characteristics ascertained at the time of chemotherapy initiation as well as those ascertained on a cycle-specific basis during the course; in particular, cycle-specific FN odds were markedly higher for regimens with an intermediate/high/unclassified FN risk level (odds ratio [OR] = 1.5-1.8), higher chemotherapy RDI (OR = 2.0), and prior FN (OR = 3.7), and were lower with use of CSF prophylaxis (OR = 0.60) (Table). Conclusions: In this retrospective evaluation of patients receiving myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or NHL, a number of risk factors were found to be important in predicting FN at the cycle level, most notably those that were ascertained on a cycle-specific basis during the chemotherapy course (e.g., chemotherapy RDI, prior FN). In addition, FN odds were found to be substantially higher for chemotherapy regimens with a high, intermediate, or unclassified (vs. low) FN risk level, and were found to be lower among patients who received CSF prophylaxis in that cycle. Careful consideration should be given to identifying patients at elevated risk of FN before administration of chemotherapy in all cycles. Disclosures Lyman: G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy; Janssen Scientific Affairs, LLC: Research Funding; Amgen Inc.: Other: Research support, Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees. Lamerato:National Cancer Institute, Centers for Disease Control and Prevention, Amgen Inc., AstraZeneca, Evidera, eMAX Health: Research Funding. Kaur:Amgen Inc., Evidera, eMAX Health: Research Funding. Shah:Amgen Inc.: Employment, Equity Ownership. Lawrence:Amgen Inc.: Employment, Equity Ownership. Silvia:Amgen Inc.: Research Funding. Hanau:Amgen Inc.: Research Funding. Weycker:Amgen Inc.: Research Funding.

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Effectiveness of Prophylaxis with Granulocyte Colony-Stimulating Factor Among Cancer Patients Receiving Myelosuppressive Chemotherapy in US Clinical Practice

Blood ◽

10.1182/blood-2019-123559 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4688-4688

Author(s):

Kathryn Richert-Boe ◽

Lois Lamerato ◽

Gary H. Lyman ◽

Manpreet Kaur ◽

Neel Shah ◽

...

Keyword(s):

Clinical Practice ◽

Health System ◽

Research Funding ◽

Cancer Colorectal ◽

Granulocyte Colony Stimulating Factor ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Study Population ◽

Equity Ownership ◽

Stimulating Factor

Introduction: Clinical practice guidelines recommend prophylaxis with granulocyte colony-stimulating factor (G-CSF) for most patients receiving chemotherapy with an intermediate risk or high risk for febrile neutropenia (FN). In real-world settings, however, many of these patients do not receive G-CSF prophylaxis, while other patients receiving low-risk or unclassified chemotherapy regimens receive G-CSF prophylaxis. Evidence on the effectiveness of G-CSF prophylaxis among diverse patient populations based on clinically rich data sources is currently limited. Methods: A retrospective cohort design and data from four US health systems-Henry Ford Health System, Kaiser Permanente Northwest, Reliant Medical Group, and Geisinger Health System-were employed. Data included patients' demographics and clinical profile, cancer, treatment, supportive care, and outcomes, and were compiled from electronic medical records systems, administrative data warehouses, medical charts, and cancer registries. The study population comprised all patients who received a course of myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or non-Hodgkin's lymphoma (NHL) from 2009-2017. For each patient, each cycle of chemotherapy during the course, and use of G-CSF primary/secondary prophylaxis and FN events in each cycle, were characterized and included as a separate observation in the analytic file; thus, each patient could contribute multiple chemotherapy cycles to the analysis. Odds ratios (OR) for FN in cycle 1 and all cycles, respectively, were estimated for patients who did versus did not receive G-CSF prophylaxis in the corresponding cycle, and odds ratios were adjusted for clustering (by patient and health system [i.e., across cycles]) as well as for differences in baseline characteristics between G-CSF prophylaxis groups using inverse probability of treatment weighting (IPTW). Results: The study population included 3,775 cancer chemotherapy patients who contributed 24,076 cycles of observation. The distribution of patients by cancer was: breast, 47%; lung, 26%; colorectal, 17%; and NHL, 10%; the distribution of patients by chemotherapy FN risk level was: high, 54%; intermediate, 12%; low, 15%; and unclassified, 19%. In cycle 1, 33% of patients received G-CSF prophylaxis (filgrastim, 53%; pegfilgrastim, 47%), and odds of FN in this subgroup were one-half those of patients who did not receive G-CSF prophylaxis (OR = 0.49 [0.35-0.67]) (Table). Across all cycles, 31% of patients received G-CSF prophylaxis (filgrastim, 55%; pegfilgrastim, 45%), and FN odds in these cycles were comparably reduced (OR = 0.76 [0.64-0.91]). Findings considering other model specifications, and across subgroups of the study population, were similar. Conclusions: In this retrospective evaluation of patients receiving myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or NHL in US clinical practice, about one-third of patients received G-CSF prophylaxis in cycle 1 and subsequent cycles, and FN incidence was significantly lower among patients who did (versus did not) receive G-CSF prophylaxis. These findings highlight the effectiveness of G-CSF prophylaxis in reducing FN risk across cycles of chemotherapy among a diverse population of cancer patients receiving myelosuppressive regimens. Disclosures Lamerato: National Cancer Institute, Centers for Disease Control and Prevention, Amgen Inc., AstraZeneca, Evidera, eMAX Health: Research Funding. Lyman:G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy; Amgen Inc.: Other: Research support, Research Funding; Janssen Scientific Affairs, LLC: Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees. Kaur:Amgen Inc., Evidera, eMAX Health: Research Funding. Shah:Amgen Inc.: Employment, Equity Ownership. Lawrence:Amgen Inc.: Employment, Equity Ownership. Silvia:Amgen Inc.: Research Funding. Hanau:Amgen Inc.: Research Funding. Weycker:Amgen Inc.: Research Funding.

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Pegfilgrastim Use Associated with Lower Risk of Hospitalization Than Filgrastim Use: A Retrospective US Claims Analysis.

Blood ◽

10.1182/blood.v116.21.3801.3801 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3801-3801 ◽

Cited By ~ 1

Author(s):

Arash Naeim ◽

Henry J Henk ◽

Laura Becker ◽

Victoria Chia ◽

Sejal Badre ◽

...

Keyword(s):

Breast Cancer ◽

Emergency Room ◽

Lower Risk ◽

Research Funding ◽

Emergency Room Visits ◽

Claims Analysis ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Equity Ownership ◽

Prophylactic Use

Abstract Abstract 3801 Objective: Patients receiving myelosuppressive chemotherapy are at risk for developing febrile neutropenia, a major dose-limiting toxicity associated with hospitalization, morbidity, and mortality. Prophylactic use of recombinant human granulocyte colony-stimulating factors (G-CSF), such as daily filgrastim and once-per-cycle pegfilgrastim, can decrease the incidence of febrile neutropenia. This study examined real-world effects of G-CSF on hospitalization risk. Methods: This retrospective U.S. claims analysis utilized data from 1/1/2004 to 2/28/2009 to examine hospitalization rates for filgrastim- and pegfilgrastim-treated patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL), breast cancer, lung cancer, ovarian cancer, and colorectal cancer. Claims with the ICD-9 code for neutropenia (288) were categorized as neutropenia-related. Cycles were included if they were 20–60 days, as defined by chemotherapy claims. G-CSF use was designated ‘prophylactic' if initiated in the first 5 days of a chemotherapy cycle, or ‘delayed', if after day 5. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by generalized estimating equations models. ORs were adjusted for potential confounders such as patient, tumor, and treatment characteristics. Healthcare utilization and costs were calculated during each cycle, as well as for emergency room, inpatient, and ambulatory visits. Cycles were considered highly myelosuppressive if patients received one or more chemotherapy agents deemed highly myelosuppressive per NCCN guidelines. Results: We identified 3,958 patients, representing 13,070 chemotherapy cycles during which G-CSF was administered (12,218 pegfilgrastim, 852 filgrastim). Most patients were female, with a mean age of 55. The most frequent cancers were breast cancer (57%), lung cancer (18%), and NHL (17%). Pegfilgrastim was used prophylactically (96% of cycles) more frequently than filgrastim (44% of cycles). Compared to chemotherapy cycles with filgrastim, those with pegfilgrastim had a decreased risk of neutropenia-related hospitalization (OR=0.33, 95% CI 0.19–0.58) and all-cause hospitalization (OR=0.56, 95% CI 0.43–0.72). Chemotherapy cycles with prophylactic initiation of either G-CSF had decreased risk of neutropenia-related hospitalization (OR=0.30, 95% CI 0.18–0.50) and all-cause hospitalization (OR=0.55, 95% CI 0.43–0.69) compared with delayed initiation of G-CSF. In subgroups of cycles with or without highly myelosuppressive chemotherapy, similar reductions in all-cause and neutropenia-related hospitalization risk were observed both with pegfilgrastim vs. filgrastim and prophylactic vs. delayed G-CSF. The two types of cycles were generally similar in patient characteristics, with the exception of proportion female, 84% vs. 67%, and baseline Deyo-Charlson comorbidity score, 4.2 vs. 5.3, for cycles with or without highly myelosuppressive chemotherapy, respectively. For all-cause utilization by cycle, the mean numbers of ambulatory visits (8.6 vs. 5.5, P<0.001) and inpatient stays (0.13 vs. 0.06, P<0.001) were greater with filgrastim as compared with pegfilgrastim, while the numbers of emergency room visits were the same (0.11 for both). For neutropenia-related utilization by cycle, there were also more ambulatory visits (1.5 vs. 0.36, P<0.001) and inpatient stays (0.02 vs. 0.01, P<0.01) with filgrastim as compared with pegfilgrastim, while mean emergency room visits were 0 for both groups. Mean total per-cycle costs (for all claims and pharmacy costs) due to all causes were similar for filgrastim and pegfilgrastim ($9,581 vs. $9,881) while mean total per-cycle costs due to neutropenia-related causes were numerically greater with filgrastim than pegfilgrastim ($1,615 vs. $1,190, P=0.054). Inpatient stays were more costly with filgrastim than pegfilgrastim for both all causes ($2,002 vs. $862, P<0.005) and neutropenia-related causes ($468 vs. $89, P=0.062). Conclusions: In this comparative effectiveness study, use of pegfilgrastim resulted in a lower risk of neutropenia-related and all-cause hospitalization compared to use of filgrastim. Inpatient stays were more frequent and more costly during cycles in which patients received filgrastim. Prophylactic use of either G-CSF was associated with a consistent reduction in hospitalization risk as compared with delayed use. Disclosures: Naeim: Amgen Inc.: Consultancy. Henk:i3 Innovus: Employment; Amgen Inc.: Research Funding. Becker:i3 Innovus: Employment; Amgen Inc.: Research Funding. Chia:Amgen Inc.: Employment, Equity Ownership. Badre:Amgen Inc.: Employment, Equity Ownership. Deeter:Amgen Inc.: Employment, Equity Ownership, Research Funding.

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ACE-011, a Soluble Activin Receptor Type Iia IgG-Fc Fusion Protein, Increases Hemoglobin (Hb) and Improves Bone Lesions in Multiple Myeloma Patients Receiving Myelosuppressive Chemotherapy: Preliminary Analysis.

Blood ◽

10.1182/blood.v114.22.749.749 ◽

2009 ◽

Vol 114 (22) ◽

pp. 749-749 ◽

Cited By ~ 11

Author(s):

Kudrat M. Abdulkadyrov ◽

Galina N. Salogub ◽

Nuriet K. Khuazheva ◽

Rachel Woolf ◽

Eric Haltom ◽

...

Keyword(s):

Breast Cancer ◽

Multiple Myeloma ◽

Placebo Group ◽

Bone Formation ◽

Fusion Protein ◽

Research Funding ◽

Receptor Type ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Equity Ownership

Abstract Abstract 749 Background: Anemia is frequently observed in multiple myeloma (MM) patients and can result from cumulative marrow suppression by chemotherapy, invasion of bone marrow by tumor cells, renal insufficiency and other causes. The vast majority of therapies approved or in development for anemia target the erythropoietin (EPO) pathway. However, recent studies suggest that the use of recombinant EPO and its derivatives may be associated with an increased risk of mortality by stimulating tumor progression and/or the occurrence of thromboembolic events. The TGF-β superfamily of proteins has been reported to play a major role in red blood cell (RBC) development, but utilizes a fundamentally different pathway from EPO. ACE-011 is a novel, fully human, fusion protein derived from the activin receptor type IIA (ActRIIA) that binds to and prevents signaling of certain members of the TGF-β superfamily through the ActRIIA receptor. In animal studies, administration of ACE-011 has been shown to increase hemoglobin and RBC levels, promote bone formation, and inhibit breast cancer and MM tumor growth. We previously reported significant increases of hemoglobin, RBC levels, and bone mineral density observed in healthy volunteers who received ACE-011 (ASH, 2008). Here, we report the preliminary results of a randomized, double-blind, placebo-controlled study of ACE-011 in MM patients receiving a regimen of melphalan, prednisolone, and thalidomide (MPT). Methods: Patients with stage II/III multiple myeloma and evidence of osteolytic bone disease were eligible to be enrolled in this study, and randomized to receive either up to 4 monthly subcutaneous (SC) doses of ACE-011 at 0.1, 0.3 and 0.5 mg/kg (n=8 each) or placebo (n=6). All patients received a standardized regimen of MPT. Patients could not have received ESAs ≤ 21 days prior to initiation or during the course of study; bisphosphonate (BP) use was allowed only as a continuation of established therapy at stable doses (≥ 2 months). Results: A total of 30 patients were enrolled. The median age was 61.5 years (ranging from 41 to 79 years). Twenty-eight patients had at least one prior MM therapy (range 1-7 prior therapies), and 13 were on stable BPs. A total of 20 patients skipped at least one dose of ACE-011 or placebo based on dose modification rules. Two patients discontinued study drug prematurely: 1 withdrew consent and 1 due to an adverse event. An SAE of sudden death, cause unknown and considered “probably”-related to MPT or “possibly”-related to ACE-011, occurred 18 days after the last dose of ACE-011 (0.1 mg/kg). Dose-dependent increases in hemoglobin were observed after the first dose of ACE-011. After the first dose, the mean maximum Hb increase was 1.3 g/dL (±1.1) in the 0.5 mg/kg cohort compared to 0.68 g/dL (±0.29) in the placebo group. On day 29 of the study, 75% patients had an increase in Hb of ≥1 g/dL in the 0.5 mg/kg cohort compared to 33% in placebo group. A hemoglobin response defined as an increase of at least 1.5 g/dL increase for consecutive 28 days during study was achieved by 10 (45%) ACE-011 treated patients and 1 (17%) patient on placebo. ACE-011 substantially increased BSAP and slightly decreased S-CTX levels among BP-naïve patients. After the first dose of ACE-011, 6 patients (20%) were reported to have ≥10 mm reduction in pain, as measured by the Visual Analog Scale (VAS), which was sustained during the study. A greater trend to improvement in osteolytic lesions by skeletal X-rays was seen in ACE-011-treated patients. Of 22 evaluable patients treated with ACE-011, 7 patients (32%) achieved a CR or VGPR. Conclusions: ACE-011 is well-tolerated and has significant hematologic activity in MM patients receiving myelosuppressive chemotherapy. ACE-011 treatment also demonstrated clinically significant increases in biomarkers of bone formation, improvement in skeletal metastases, decreases in bone pain, and anti-tumor activity. The unique pharmacology of ACE-011 enables it to address multiple complications of MM, and presents a novel target to treat the underlying disease as well. These findings also demonstrate that ACE-011 has potential as a novel therapy for chemotherapy-induced anemia and may be an effective alternative to EPO-based treatments. To further explore the potential of this novel agent, a phase 2 study investigating ACE-011 in metastatic breast cancer patients with chemotherapy-induced anemia is currently underway. This study was supported in part by a grant from the Multiple Myeloma Research Foundation. Disclosures: Abdulkadyrov: Acceleron: Research Funding. Salogub:Acceleron: Research Funding. Khuazheva:Acceleron: Research Funding. Woolf:Acceleron: Employment, Equity Ownership. Haltom:Acceleron: Employment, Equity Ownership. Borgstein:Acceleron: Employment, Equity Ownership. Knight:Celgene: Employment, Equity Ownership. Renshaw:Celgene: Employment, Equity Ownership. Yang:Acceleron: Employment, Equity Ownership. Sherman:Acceleron: Employment, Equity Ownership.

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Risk Factors For Bone Pain Among Patients Receiving Myelosuppressive Chemotherapy and Primary Prophylactic Pegfilgrastim

Blood ◽

10.1182/blood.v122.21.1710.1710 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1710-1710

Author(s):

Hairong Xu ◽

Qi Gong ◽

Florian D Vogl ◽

Esteban Abella ◽

John H Page

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Risk Factors ◽

Bone Pain ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Increased Risk ◽

History Of ◽

Equity Ownership ◽

Reduced Risk

Abstract Introduction Febrile neutropenia (FN) is a common, life-threatening side effect of myelosuppressive chemotherapy. Prophylactic pegfilgrastim (Neulasta) beginning with the first cycle of chemotherapy has been shown to reduce the incidence of FN (Vogel CL et al., J Clin Oncol., 2005). Bone pain is the most common adverse event associated with pegfilgrastim, and most incidences of bone pain can be managed with nonsteroidal anti-inflammatory drugs (NSAIDs). However, little is known about risk factors for bone pain in patients treated with pegfilgrastim. Methods This study used individual patient data from 23 Amgen-sponsored, randomized clinical trials and included adults receiving myelosuppressive chemotherapy and primary prophylactic pegfilgrastim. Bone pain was identified based on the adverse events reported in the trials. Multivariable logistic regression models were used to identify risk factors associated with the occurrence of moderate to severe bone pain (grade 2+) in cycle 1 (the primary outcome) and across cycles 1-6 and any grade bone pain in cycle 1 and across cycles 1-6. Data collected in the trials and included in the regression model include baseline patient characteristics (gender, race, and age); disease characteristics (primary tumor type and tumor stage); treatment characteristics (taxane vs no taxane treatment and dose of pegfilgrastim); and medical history (osteoporosis/osteopenia, hypercholesterolemia, anemia, neutropenia, osteomyelitis/osteonecrosis, arthritis, peripheral neuropathy, chronic fatigue syndrome, gout, bone fracture, and bone pain). Results This study included data from 1974 patients who received myelosuppressive chemotherapy and primary prophylactic pegfilgrastim. The most frequent tumor types in the study sample were breast cancer (54.8%), non-small cell lung cancer (17.1%), and non-Hodgkins lymphoma (13.6%). 41.2% of patients had stage IV disease. Grade 2+ bone pain was reported in 372 patients (18.8%) in cycle 1 and 564 patients (28.6%) across the first 6 cycles, while any grade bone pain was reported in 709 patients (35.9%) in cycle 1 and 1016 patients (51.5%) across the first 6 cycles. In the first cycle of chemotherapy, previous history of osteoporosis/osteopenia (odds ratio [OR] 1.28; 95% CI 1.04-1.56), gout (1.44; 0.98-2.13), and bone pain (1.28; 1.09-1.49), and pegfilgrastim dose (100 mcg/kg vs a fixed dose of 6 mg; 1.68; 1.13-2.51) were associated with increased risk of grade 2+ bone pain; compared with breast cancer, colorectal cancer was associated with reduced risk of grade 2+ bone pain (0.26; 0.11-0.60) and ovarian cancer with increased risk of grade 2+ bone pain (1.89; 0.98-3.64); compared with age <45 years, age ≥65 years was associated with reduced risk of grade 2+ bone pain (0.80; 0.63-1.01) (table). Conclusions History of osteoporosis/osteopenia, history of bone pain, breast cancer (vs colorectal cancer), and younger age appear to be risk factors for bone pain in chemotherapy-treated patients who received primary prophylactic pegfilgrastim. The study results may be used to identify patients at increased risk of bone pain who may benefit from pain therapy. Disclosures: Xu: Amgen Inc. : Employment, Equity Ownership. Gong:Amgen Inc. : Employment, Equity Ownership. Vogl:Amgen Inc. : Employment, Equity Ownership. Abella:Amgen Inc. : Employment. Page:Amgen Inc. : Employment, Equity Ownership.

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Risk Factors for Febrile Neutropenia among Breast, Lung, and Colorectal Cancer Patients: A Retrospective Analysis of Health Plan Databases

Blood ◽

10.1182/blood.v112.11.4696.4696 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4696-4696

Author(s):

Scott Davi d Ramsey ◽

Jeannine S McCune ◽

David K Blough ◽

Lauren C Clarke ◽

Cara L McDermott ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Lung Cancer ◽

Cancer Patients ◽

Chemotherapy Regimen ◽

Patient Factors ◽

Myelosuppressive Chemotherapy ◽

Chemotherapy Administration ◽

Factors Influencing ◽

Colorectal Cancer Patients

Abstract Chemotherapy regimens, patient factors, and the use of colony stimulating factor (CSF) influence cancer patients’ risk for febrile neutropenia (FN) when they receive myelosuppressive chemotherapy. The incidence of FN and patient factors influencing that risk are relatively unknown in community settings. Using claims from Medicare, Medicaid and two private health insurance plan enrollees linked to the Puget Sound SEER registry, we examined the incidence of FN among breast, lung and colorectal cancer patients diagnosed 2002–05 who received adjuvant chemotherapy. We used logistic regression models to determine factors influencing the risk for FN within the first chemotherapy cycle, controlling for cancer stage, age, sex, race, comorbidities, chemotherapy-regimen related FN risk (as designated by the National Comprehensive Cancer Network), CSF use, health insurance type, and surgery or radiation ≤30 days from administration of first chemotherapy. Over the time horizon, 1096 breast, 1142 lung, and 755 colorectal cancer patients received chemotherapy. The incidence of any FN in the first chemotherapy cycle was (counts per 100 recipients by high, intermediate, and low-risk myelosuppressive chemotherapy according to NCCN categories respectively) 7.36, 10.0, 4.70 for breast cancer, 17.12, 14.15, 12.22 for lung cancer, and 25.0, 8.96, 6.37 for colorectal cancer. Significant predictors (p<0.05) of any FN were: breast cancer—radiation ≤ 30 days from first chemotherapy administration (OR 2.90, 95% CI 1.21–6.94), other non-black race vs. white race (OR 2.82, 95% CI 1.29–6.17), or Medicaid insurance (OR 2.31, 95% CI 1.10–4.89); lung cancer—radiation ≤ 30 days from first chemotherapy administration (OR 1.63, 95% CI 1.01–2.61), surgery ≤ 30 days from first chemotherapy administration (OR 2.08, 95% CI 1.02–4.25), Medicaid insurance (OR 2.29, 95% CI 1.08–4.84), or a Charlson comorbidity score ≥ 2 (OR 2.56, 95% CI 1.11–5.91); colorectal cancer—female gender (OR 1.86, 95% CI 1.02–3.41) or high myelosuppressive risk chemotherapy regimen (OR 7.66, 95% CI 2.95–19.89). In this analysis, predictors of FN varied between cancers. Limitations of this analysis include lack of information about chemotherapy and CSF doses, as this is not captured in the SEER registry or claims data. These results indicate that several factors may interact to influence a patient’s likelihood of developing FN in the first cycle of adjuvant chemotherapy.

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Clinic Staff Time and Labor Costs Associated with Administering Pegfilgrastim as Compared with Filgrastim to Patients Receiving Myelosuppressive Chemotherapy: Results of a Health Economic Model

Blood ◽

10.1182/blood.v116.21.1515.1515 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1515-1515

Author(s):

Douglas C.A. Taylor ◽

Michelle Skornecki ◽

Gregory Hill ◽

Richard Barron ◽

Chris Anstead ◽

...

Keyword(s):

Febrile Neutropenia ◽

Research Funding ◽

Opportunity Costs ◽

Labor Costs ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Community Oncology ◽

Equity Ownership ◽

Delivery Scheduling ◽

Delivery Models

Abstract Abstract 1515 Objective: Patients receiving myelosuppressive chemotherapy are at risk for developing febrile neutropenia, a major dose-limiting toxicity of systemic chemotherapy. Prophylactic use of recombinant human granulocyte colony-stimulating factors (G-CSF), such as filgrastim used daily for up to two weeks and pegfilgrastim used once per cycle, decreases the incidence of febrile neutropenia. Cancer delivery models are under pressure to become more efficient in an increasingly cost-restrictive environment. The use of growth factors to help prevent febrile neutropenia is well established, but little is known regarding the use of practice resources necessary to deliver therapy. The objective of this study was to construct an empirical model to calculate the human resource time and cost associated with delivery of filgrastim and pegfilgrastim. Methods: A practice-level model was constructed detailing staff tasks required for the administration of G-CSF on a monthly basis. Key model inputs include specific clinic characteristics, such as the number of patients treated with G-CSF, the number of filgrastim injections administered per cycle, and hourly pay rates for nurses and clerks. As described by Fortner et al (Community Oncology 2004, 1:23-28), interviews were conducted with 400 medical professionals at 20 US community oncology practices to provide data for the time required for the tasks involved in G-CSF delivery (scheduling, front desk, phlebotomy, laboratory, triage, injection, and billing). Model outputs were time expended for each staff type for administration of filgrastim or pegfilgrastim and corresponding labor costs. Costs for drug (filgrastim or pegfilgrastim), laboratory tests, and other materials were excluded from this model. The base-case scenarios contrasted 1 patient vs. 30 patients per month. Also examined were results for patients who received 11 injections of filgrastim per chemotherapy cycle, reflecting the mean number of injections received per cycle in the pegfilgrastim registrational clinical trials, and patients receiving 6 injections per cycle, as observed in current clinical practice. Using Bureau of Labor Statistics data, hourly pay rates were assumed to be $31.28 for nurses and $12.35 for clerks. Results: Table 1 displays monthly opportunity costs in hours and dollars of using once-per-cycle pegfilgrastim injection as compared with filgrastim given as either 6 or 11 injections per cycle. Alternate cost and time assumptions, with 95% confidence intervals for salary and time inputs, are shown in parentheses. Conclusions: The 30-patient model predicts monthly opportunity costs with pegfilgrastim as compared with filgrastim of 378 to 756 staff hours and between $9,000 and $18,000. On a per-patient basis, the monthly opportunity cost would be 13 to 25 staff hours and $300 to $600. Use of pegfilgrastim as compared with filgrastim is associated with substantial savings in time and labor costs. Future medical care delivery models should consider practice resource requirements as a means of increasing efficiency and cost effectiveness. Disclosures: Taylor: i3 Innovus: Employment; Amgen Inc.: Consultancy, Research Funding. Skornecki:i3 Innovus: Employment; Amgen Inc.: Consultancy, Research Funding. Hill:i3 Innovus: Employment; Amgen Inc.: Consultancy, Research Funding. Barron:Amgen Inc.: Employment, Equity Ownership, Research Funding. Anstead:Amgen Inc.: Employment, Equity Ownership. Fortner:P4 Healthcare: Employment. Ozer-Deniz:i3 Innovus: Employment; Amgen Inc.: Consultancy, Research Funding.

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Same-Day Administration of Pegfilgrastim Following Myelosuppressive Chemotherapy: Practices and Rationale

Blood ◽

10.1182/blood.v126.23.5585.5585 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5585-5585

Author(s):

Christina Darden ◽

Mark A. Price ◽

James A. Kaye ◽

Bintu Sherif ◽

Sarah Marion ◽

...

Keyword(s):

Febrile Neutropenia ◽

Patient Outcomes ◽

Clinical Judgment ◽

Research Funding ◽

Employment Equity ◽

Related Factors ◽

Myelosuppressive Chemotherapy ◽

Equity Ownership ◽

Prescribing Information

Abstract Introduction: Granulocyte colony-stimulating factors such as pegfilgrastim (Neulasta®) can reduce the incidence of febrile neutropenia, a life-threatening side effect of myelosuppressive chemotherapy. According to current FDA-approved prescribing information, pegfilgrastim should not be administered between 14 days before and 24 hours after administration of myelosuppressive chemotherapy. Previous research indicates that same- vs next-day administration of pegfilgrastim may be associated with worse patient outcomes, and current guidelines from both ASCO and NCCN recommend use of pegfilgrastim 1-3 days after chemotherapy. A recent health care claims database analysis has shown that same-day pegfilgrastim was administered in ~13% of chemotherapy cycles, but little is known about physician rationale for administering same-day pegfilgrastim. Here, we describe the results of a cross-sectional, web-based physician survey describing the practice- and patient-related factors that physicians report to have affected their decision to administer same-day pegfilgrastim. Methods: Survey invitations were sent via e-mail to a sample of US medical oncologists, hematologists, and hematologist-oncologists who were enrolled in a national physician panel. Physicians who reported experience prescribing same-day pegfilgrastim within the last 6 months and provided informed consent were included. Physician reasons for prescribing same-day pegfilgrastim were assessed. The analysis was descriptive; summary statistics are presented. Results: Of 17,478 physicians who were invited to participate, 386 were screened, and 186 (48%) reported administering same-day pegfilgrastim within the previous 6 months. A total of 183 physicians (47%) agreed to participate in the survey, and 151 (39%) completed the survey. Mean (SD) years in practice was 14.6 (8.2) years. Most physicians practiced in a private group practice (39%), at a cancer hospital/referral center (25%), or at other types of academic hospitals/clinics (23%). Physicians were relatively evenly distributed across the US and most (54%) practiced in towns with a population ≥250,000. Breast cancer and non-small cell lung cancer were the most common primary cancers in patients followed by the physicians. Physicians estimated that ~41% of their patients received pegfilgrastim, and that among patients who received pegfilgrastim, ~32% received same-day pegfilgrastim, with ~43% of those patients receiving same-day pegfilgrastim across all chemotherapy cycles. 36% of physicians relied primarily on clinical judgment when deciding to administer same-day pegfilgrastim. The most common patient risk factors reported by physicians as moderately or very important when deciding to administer same-day pegfilgrastim were previous febrile neutropenia (78%), presence of infection or open wounds (70%), and poor ECOG performance status (67%). When asked to rank 7 different clinical and logistic reasons to administer same-day pegfilgrastim (with 1 being most important), "it was more practical for the patient" was the most important reason (mean rank = 3.0; SD = 1.7), and "it was more practical for the practice due to patient scheduling burden/load" was the least important (mean rank = 4.2; SD = 1.7). 85% of physicians reported travel distance for the patient/caregiver and 79% reported method or availability of transportation for the patient/caregiver as moderately or very important patient-related factors for same-day administration of pegfilgrastim. The most important administrative consideration for same-day administration of pegfilgrastim was burden of actual prophylactic administration of pegfilgrastim on the next day and follow-up (65% of physicians cited as moderately or very important). Conclusions: Physicians rely primarily on clinical judgment when deciding whether to administer same-day pegfilgrastim, and clinical risk factors such as previous febrile neutropenia affect the decision to administer same-day pegfilgrastim. Additional physician considerations include patient/caregiver travel distance, method or availability of transportation, and burden of actual prophylactic administration of pegfilgrastim on the next day and follow-up. Continued education of patients and physicians on the potential risks of same-day pegfilgrastim administration could increase compliance and improve patient outcomes. Disclosures Darden: Amgen Inc: Research Funding; RTI Health Solutions: Employment. Off Label Use: This abstract assesses physician rationale for same-day administration of pegfilgrastim, which is an off-label use of pegfilgrastim. As noted in the abstract text, "According to current FDA-approved prescribing information, pegfilgrastim should not be administered between 14 days before and 24 hours after administration of myelosuppressive chemotherapy.". Price:Amgen Inc.: Research Funding; RTI Health Solutions: Employment. Kaye:Amgen Inc.: Research Funding; RTI Health Solutions: Employment. Sherif:Amgen Inc.: Research Funding; RTI Health Solutions: Employment. Marion:RTI Health Solutions: Employment; Amgen Inc.: Research Funding. Tzivelekis:Amgen Inc.: Employment, Equity Ownership. Garcia:Amgen Inc: Employment, Equity Ownership. Chandler:Amgen Inc.: Employment, Equity Ownership.

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Risk of Infection Among Patients with Non-Metastatic Solid Tumors or Non-Hodgkin’s Lymphoma Receiving Myelosuppressive Chemotherapy and Antimicrobial Prophylaxis in US Clinical Practice

Blood ◽

10.1182/blood.v122.21.1730.1730 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1730-1730

Author(s):

Derek Weycker ◽

David Chandler ◽

Rich Barron ◽

Hairong Xu ◽

Hongsheng Wu ◽

...

Keyword(s):

Clinical Practice ◽

Solid Tumors ◽

Research Funding ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Employment Equity ◽

Myelosuppressive Chemotherapy ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Equity Ownership

Abstract Background Clinical practice guidelines recommend oral antimicrobials (AMB)—principally, the fluoroquinolones—for prophylaxis against chemotherapy-related infections (CRI) in intermediate- and high-risk patients undergoing myelosuppressive chemotherapy. Available evidence on the risk of CRI among patients with non-metastatic solid tumors or non-Hodgkin's lymphoma (NHL) receiving myelosuppressive chemotherapy and AMB prophylaxis in US clinical practice is currently limited. Methods A retrospective cohort design and data from two US private healthcare claims repositories (2008-2011) were employed. The study population included adult patients who received myelosuppressive chemotherapy for non-metastatic cancer of the breast, colon/rectum, or lung, or for NHL. For each study subject, the first qualifying chemotherapy course, and each chemotherapy cycle and episode of CRI within the course, were identified. Use of prophylaxis with oral AMB agents—including antibacterial, antifungal, and antiviral drugs—as well as colony-stimulating factors (CSF) in each cycle also was identified. CRI was ascertained based on admission to an acute-care inpatient facility with a corresponding diagnosis (1⁰ or 2⁰) or an ambulatory encounter with a corresponding diagnosis and evidence of AMB therapy. Risk of CRI was evaluated during chemotherapy cycles in which patients received AMB prophylaxis; only results for the most frequently observed regimen for each tumor type are reported herein. Results The most common regimens—by tumor—were: breast cancer, docetaxel + cyclophosphamide (“TC”, 29% of 34,876); colorectal cancer, folinic acid (leucovorin) + fluorouracil + oxaliplatin (“FOLFOX”, 34% of 14,334); lung cancer, paclitaxel + carboplatin (“PC”, 25% of 17,334); and NHL, cyclophosphamide + doxorubicin + vincristine + prednisone with Rituxan (“CHOP-R”, 45% of 9,612). Across these four regimens, use of AMB prophylaxis in cycle 1 ranged from 3.5-8.6%; fluoroquinolones were the most common agents administered (range, 27.1-43.5%) (Table 1). Use of CSF prophylaxis in cycle 1 ranged from 10.4-61.2%. Among subjects who received first-cycle AMB prophylaxis, risk of CRI in that cycle ranged from 1.2-7.5%; among these subjects, 45-68% had CRI in the inpatient setting (Table 2). CRI risks in subsequent cycles with AMB prophylaxis were generally comparable. Conclusion Among patients with non-metastatic solid tumors or NHL receiving common myelosuppressive chemotherapy and AMB prophylaxis in US clinical practice, risk of CRI ranged from 1.2-8.6% in cycles in which AMB prophylaxis was administered. Disclosures: Weycker: Amgen Inc.: Research Funding. Chandler:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership. Xu:Amgen Inc.: Employment, Equity Ownership. Wu:Amgen Inc.: Research Funding. Girardi:Amgen Inc.: Employment, Equity Ownership. Edelsberg:Amgen Inc.: Research Funding. Lyman:Amgen Inc.: PI on a research grant to Duke University Other.

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