Use Of Pegfilgrastim Primary Prophylaxis By Chemotherapy Cycle Among Patients With Non-Hodgkin’s Lymphoma Or Breast Cancer

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5598-5598
Author(s):  
Wendy J Langeberg ◽  
Conchitina C Siozon ◽  
PK Morrow ◽  
John H Page ◽  
Victoria M Chia

Abstract Introduction A recent open-label, randomized, phase III study in patients with breast cancer (BC) treated with myelosuppressive chemotherapy found a 3-fold higher incidence of febrile neutropenia (FN) among patients who received pegfilgrastim (peg) prophylaxis during the first two chemotherapy cycles only compared with those who received peg prophylaxis during all chemotherapy cycles (36% vs 10%, respectively; Aarts et al. Journal of Clinical Oncology, April 29, 2013). We examined the use of peg prophylaxis in a real-world setting to assess if practice conforms to clinical guidelines, which recommend granulocyte colony-stimulating factor (G-CSF) every chemotherapy cycle where the risk of FN is ≥20%. Methods The study cohort was selected from the MarketScan Research Database of administrative claims maintained by Truven Health Analytics. The selection criteria included adults diagnosed with non-Hodgkin's lymphoma (NHL) or female BC who began chemotherapy between January 1, 2005 and December 31, 2010. Patients were excluded if they received filgrastim, radiotherapy, or a bone marrow or stem cell transplant during their first chemotherapy course. The proportion of patients in the study cohort who received peg prophylaxis was calculated during cycle 1. For each subsequent cycle, the proportion of patients who received peg prophylaxis was calculated among the patients who had received peg in cycle 1 and continued on the same regimen. Results Table 1 shows the use of peg prophylaxis among patients with NHL who received CHOP (cyclophosphomide, doxorubicin, vincristine, prednisone), with or without rituxumab (R) in cycle 1, for 2-week (Q2W) or 3-week (Q3W) cycles, and did not receive filgrastim during their course. Of the 81 patients who received CHOP or CHOP-R Q2W, 61% received peg in cycle 1; of those who remained on the regimen, 74% to 95% received peg in subsequent cycles. Of the 892 patients who received CHOP or CHOP-R Q3W, 54% received peg in cycle 1; of those who remained on the regimen, 90%-95% received peg in subsequent cycles. Table 2 shows the use of peg among patients with BC who received TAC (docetaxel, doxorubicin, cyclophosphamide), ddAC-T (dose-dense doxorubicin, cyclophosphamide followed by dose-dense paclitaxel), or TC (docetaxel, cyclophosphamide) in cycle 1 and did not receive filgrastim during their course. Of the 1,730 patients who received TAC, 78% received peg in cycle 1; of those who remained on the regimen, 88% to 94% received peg in subsequent cycles. Of the 3,170 patients who received ddAC-T, 76% received peg in cycle 1; of those who remained on the regimen, 86% to 93% received peg cycles 2 to 4. Of the 3,639 patients who received TC, 51% received peg in cycle 1; of those who remained on the regimen, about 90% received peg in subsequent cycles. Conclusions Despite clinical guidelines recommending G-CSF prophylaxis with chemotherapy regimens with a high risk of FN, many NHL and BC patients do not receive appropriate FN prophylaxis. However, among NHL and BC patients who receive peg in cycle 1 and remain on the regimen, the majority appear to continue prophylaxis as indicated. The dataset has some limitations: we could not determine dose, complete risk factors for FN, or reasons patients did not receive or discontinued peg. Disclosures: Langeberg: Amgen: Employment, Equity Ownership. Siozon:Amgen: Employment. Morrow:Amgen: Employment, Equity Ownership. Page:Amgen Inc. : Employment, Equity Ownership. Chia:Amgen: Employment, Equity Ownership.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2161-2161 ◽  
Author(s):  
Jun Chen ◽  
Sha Jin ◽  
Paul Tapang ◽  
Stephen K Tahir ◽  
Morey Smith ◽  
...  

Abstract All authors are employees of AbbVie and participated in the design, conduct, and interpretation of these studies. AbbVie and Genentech provided financial support for these studies and participated in the review and approval of this publication. The BCL-2-selective inhibitor ABT-199 has demonstrated efficacy in numerous preclinical models of hematologic malignancies without causing thrombocytopenia, a dose-limiting toxicity associated with the BCL-2/BCL-XL inhibitor navitoclax (Souers et al. 2013. Nat. Med. 19, 202-208). ABT-199 has also demonstrated clinical activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL) (Seymour et al. 2014. J. Clin. Oncol. 32, 448s; Davids et al. 2014. J. Clin. Oncol. 32, 544s). Despite these encouraging early clinical data, some subjects do not respond to ABT-199 or progress while on treatment. Pre-clinical models indicate that both intrinsic and acquired resistance may be a consequence of MCL-1 expression. Consequently, we have explored potent and selective small molecule inhibitors of CDK9, a kinase known to maintain the expression of MCL-1 through its role in p-TEFb-mediated transcription. Inhibition of CDK9 resulted in the rapid loss in RNA polymerase II phosphorylation (Serine 5) and MCL-1 expression that was closely followed by the induction of apoptosis in MCL-1-dependent cell lines, a cellular response that could be rescued by overexpression of BCL-2. Substantial synergy was observed between CDK9 inhibitors and ABT-199 in a number of hematologic cell lines with intrinsic or acquired resistance to ABT-199. Direct inhibition of MCL-1 with the small molecule BH3 mimetic A-1210477 was also highly synergistic with ABT-199, further validating the utility of co-inhibiting MCL-1 and BCL-2 function simultaneously in ABT-199 resistant tumors. Importantly, the CDK9 inhibitor-ABT-199 combination was well tolerated in vivo and demonstrated efficacy superior to either agent alone in xenograft models of non-Hodgkin’s lymphoma (NHL) and acute myelogenous leukemia (AML). These data indicate that CDK9 inhibitors may be highly efficacious when used in combination with ABT-199 for the treatment of hematologic malignancies. Disclosures Chen: Abbvie: Employment, Equity Ownership. Jin:Abbvie: Employment, Equity Ownership. Tapang:abbvie: Employment, Equity Ownership. Tahir:abbvie: Employment, Equity Ownership. Smith:abbvie: Employment, Equity Ownership. Xue:abbvie: Employment, Equity Ownership. Zhang:abbvie: Employment, Equity Ownership. Gao:abbvie: Employment, Equity Ownership. Tong:abbvie: Employment, Equity Ownership. Clark:abbvie: Employment, Equity Ownership. Ricker:abbvie: Employment, Equity Ownership. Penning:abbvie: Employment, Equity Ownership. Albert:abbvie: Employment, Equity Ownership. Phillips:abbvie: Employment, Equity Ownership. Souers:abbvie: Employment, Equity Ownership. Leverson:abbvie: Employment, Equity Ownership.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1730-1730
Author(s):  
Derek Weycker ◽  
David Chandler ◽  
Rich Barron ◽  
Hairong Xu ◽  
Hongsheng Wu ◽  
...  

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.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5229-5229 ◽  
Author(s):  
Roy Louis Maute ◽  
James Y Chen ◽  
Kristopher David Marjon ◽  
Jiaqi Duan ◽  
Timothy Choi ◽  
...  

Introduction Magrolimab (Hu5F9-G4, 5F9) is a first-in-class IgG4 antibody targeting CD47, a macrophage immune checkpoint and "don't eat me" signal expressed on cancer cells. Blockade of CD47 leads to phagocytosis of tumor cells. Magrolimab synergizes with rituximab to eliminate CD20-positive lymphoma by enhancing antibody-dependent cellular phagocytosis. Magrolimab +rituximab demonstrated encouraging safety and efficacy in a Phase (Ph)1b dose escalation cohort in patients with relapsed/refractory (r/r) DLBCL and FL that were rituximab-refractory (Advani et al., NEJM 2018). CD24 is an additional "don't eat me" signal, and has been proposed as a potential target for immunotherapy (Barkal et al. Nature 2019). Here we describe immunohistochemical analysis of CD47 and CD24 in primary patient biopsies from an ongoing follow-up Phase 2 trial of Non-Hodgkin's lymphoma (including DLBCL and indolent lymphoma) patients treated with magrolimab+rituximab. Results By immunohistochemistry, 54 out of 54 patients assessed were positive for expression of CD47 at screening. High levels of CD47 expression were maintained during treatment with clinically-efficacious doses of magrolimab. Therapeutic response did not correlate with CD47 H-score expression levels. At screening, patients presented with highly variable levels of CD24 expression, with 40 of 54 samples showing positive staining in >30% of cells. We observed no significant correlation between CD24 expression by H-score and response to therapy (complete response + partial response) in either DLBCL or indolent lymphoma. Conclusions CD47 shows consistently high expression in primary biopsies from Non-Hodgkin's lymphoma patients and remains persistently high during treatment. In our Phase 2 trial, therapeutic response did not correlate with CD47 expression levels, suggesting that the degree of target expression is not a primary driver of magrolimab efficacy in Non-Hodgkin's lymphoma. Although we observe wide variation in CD24 expression within this cohort, its levels are not predictive of outcome for this disease indication. We are evaluating the expression of additional biomarkers to identify those Non-Hodgkin's lymphoma patients most likely to benefit from magrolimab+rituximab combination therapy. Disclosures Maute: Forty Seven Inc.: Employment, Equity Ownership, Patents & Royalties. Chen:Forty Seven Inc.: Consultancy, Equity Ownership. Marjon:Forty Seven Inc.: Employment, Equity Ownership. Duan:Forty Seven Inc.: Employment, Equity Ownership. Choi:Forty Seven Inc.: Employment, Equity Ownership. Chao:Forty Seven, Inc.: Employment, Equity Ownership, Patents & Royalties. Takimoto:Forty Seven, Inc.: Employment, Equity Ownership, Patents & Royalties. Agoram:Forty Seven Inc.: Employment, Equity Ownership. Volkmer:Forty Seven, Inc.: Employment, Equity Ownership, Patents & Royalties.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3697-3697
Author(s):  
Michael J. Robertson ◽  
John Bauman ◽  
Olivia Gardner ◽  
Zdenka Jonak ◽  
Herbert Struemper ◽  
...  

Abstract Abstract 3697 Background: Iboctadekin (recombinant human interleukin-18; rhIL-18) is an immunostimulatory cytokine with anti-tumor activity in preclinical animal models. Phase I clinical trials have demonstrated that rhIL-18 is well-tolerated as monotherapy for patients with advanced solid tumors. Preclinical and clinical data indicate that rhIL-18 acts a costimulatory cytokine that may be optimally used in combination with other agents such as monoclonal antibodies. Methods: Patients with CD20+ B-cell non-Hodgkin's lymphoma (NHL) were given rituximab 375 mg/m2 IV weekly for 4 consecutive weeks in combination with rhIL-18 (in six dose cohorts of 1, 3, 10, 20, 30, and 100 mcg/kg) IV weekly for 12 weeks. Eligible patients had disease which progressed after standard therapy or for which there was no effective standard treatment. Assessments included safety/tolerability, pharmacokinetics, pharmacodynamics (serum cytokines, peripheral blood phenotypic markers and tumor biomarkers), immunogenicity, and anti-tumor activity. Results: Nineteen patients were enrolled on study (10 follicular NHL, 5 mantle cell lymphoma, 2 diffuse large B-NHL, 2 other subtypes). The combination was well-tolerated with a safety profile similar to that observed with rituximab or rhIL-18 given as monotherapy. The pharmacodynamic response is as expected based on results of prior clinical trials of rhIL-18 as monotherapy for cancer. Using the IWC response criteria, two (11%) of 18 evaluable patients had complete responses (CR) and 3 (16%) had partial responses (PR). Six (33%) patients had stable disease. Overall response rate for follicular lymphoma was 33% (1 CR, 2 PR). Conclusions: The combination of rhIL-18 and rituximab is safe, well-tolerated, and induces potent biological activity. A maximum tolerated dose of rhIL-18 was not identified. Further study of rhIL-18 plus rituximab in patients with CD20+ B cell malignancies is warranted. Disclosures: Bauman: GlaxoSmithKline: Employment, Equity Ownership. Gardner:GlaxoSmithKline: Employment, Equity Ownership. Jonak:GlaxoSmithKline: Employment, Equity Ownership. Struemper:GlaxoSmithKline: Employment, Equity Ownership. Germaschewski:GlaxoSmithKline: Employment, Equity Ownership. Koch:GlaxoSmithKline: Employment, Equity Ownership. Murray:GlaxoSmithKline: Employment, Equity Ownership. Toso:GlaxoSmithKline: Employment, Equity Ownership.


2009 ◽  
Vol 23 (6) ◽  
pp. 387-393 ◽  
Author(s):  
Karen Brajão de Oliveira ◽  
Julie Massayo Maeda Oda ◽  
Julio Cesar Voltarelli ◽  
Thiago Franco Nasser ◽  
Mario Augusto Ono ◽  
...  

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