Cost-Effectiveness Of Lenalidomide and Bortezomib In Patients With Previously Untreated Multiple Myeloma (MM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5604-5604 ◽  
Author(s):  
Gerry Oster ◽  
Ariel Berger ◽  
Rebecca Bornheimer ◽  
Gary Binder ◽  
Yasir Nagarwala
Keyword(s):  
Multiple Myeloma ◽  
Cost Effectiveness ◽  
Incremental Cost ◽  
Research Funding ◽  
Quality Adjusted Life Year ◽  
Novel Agents ◽  
Published Data ◽  
Employment Equity ◽  
Equity Ownership ◽  
Quality Adjusted Life

Abstract Introduction The efficacy and safety of the novel agents, lenalidomide and bortezomib, in previously untreated MM has been demonstrated in several randomized controlled trials (Online-OnlyTs). In this study, we examine the cost-effectiveness of lenalidomide-melphalan–prednisone induction followed by lenalidomide maintenance (MPR-R), and bortezomib-melphalan-prednisone (VMP), respectively, versus melphalan-prednisone (MP), in patients with previously untreated MM. Methods We developed a partitioned-survival model to estimate expected clinical outcomes and costs in newly diagnosed MM patients receiving MPR-R, VMP, or MP as first-line therapy. The model had 3 mutually exclusive health states: (1) “progression-free, alive”; (2) “post-progression, alive”; and (3) “death.”  Progression-free survival (PFS) for MP was estimated by aggregating data across five Online-OnlyTs (Palumbo 2012, San Miguel 2008, Facon 2007, Hulin 2009, Palumbo 2006). Estimates of PFS for MPR-R and VMP were based on an adjusted indirect treatment comparison with MP, using data from MM-015 for MPR-R (Palumbo 2012) and VISTA for VMP (San Miguel 2008). Since many MP patients in both MM-015 and VISTA “crossed over” to lenalidomide and bortezomib following disease progression in these trials, we estimated post-progression survival (PPS) for MPR-R and VMP based on a review of novel agents in MM (Messori 2011), which reported mean PPS of 30.9 months. Costs of MPR-R and VMP were estimated based on actual use of study drug in Online-OnlyTs; costs of adverse events as well as other disease-related costs were estimated based on published data. Health-state utilities also were estimated using published data.  All costs were expressed in 2012 US$.  Cost-effectiveness of MPR-R and VMP versus MP was examined in terms of cost per life-year (LY) gained, cost per quality-adjusted life-year (QALY) gained, and cost per progression-free life-year gained.  Future costs and benefits were discounted at 3% annually. Results Mean estimated PFS was 3.4 years for MPR-R, 2.6 years for VMP, and 1.7 years for MP; corresponding estimates for OS were 6.0 years, 5.2 years, and 4.3 years, respectively (Table 1). Mean total expected lifetime costs (discounted) are reported in the Table. The incremental cost per life-year (LY) gained versus MP was $75,392 for MPR-R and $86,213 for VMP; corresponding estimates of the incremental cost per QALY gained were $91,794 and $106,211, respectively (Figure 1).  The incremental cost per progression-free LY (PFLY) gained versus MP was $70,666 for MPR-R and $80,565 for VMP. Conclusions In patients with previously untreated MM, cost-effectiveness ratios for MPR-R and VMP are well within the range reported for other well-accepted novel therapies in oncology. $/LY: Incremental cost per life-year gained; $/QALY: Incremental cost per quality-adjusted life-year gained; $/PFLY: Incremental cost per progression-free life-year gained Support Funded by Celgene Corporation Disclosures: Oster: Celgene: Research Funding. Off Label Use: Lenalidomide (immunomodulatory agent), bortezomib (proteosome inhibitor), melphalan (alkylator), and prednisone (steroid), are all treatments for multiple myeloma. Berger:Celgene: Research Funding. Bornheimer:Celgene: Research Funding. Binder:Celgene: Employment, Equity Ownership. Nagarwala:Celgene: Employment, Equity Ownership.

The Cost-Effectiveness of Bortezomib for the Initial Treatment of Multiple Myeloma in the United States.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1379-1379
Author(s):  
Si-Tien Wang ◽  
Hui Huang ◽  
Hongliang Shi ◽  
Mei Sheng Duh ◽  
Kristina Chen ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Health Outcomes ◽  
Incremental Cost ◽  
Research Funding ◽  
The United States ◽  
Line Treatment ◽  
Second Line ◽  
Employment Equity ◽  
Equity Ownership ◽  
The Cost

Abstract Abstract 1379 Poster Board I-401 Background: Data from the phase III VISTA trial demonstrated superiority in terms of clinical effectiveness of bortezomib (Velcadë) plus melphalan and prednisone (VMP) relative to melphalan and prednisone alone (MP) in the initial treatment of patients with multiple myeloma (MM). The aim of this study was to utilize data from the VISTA study and published literature to compare lifetime health outcomes and the cost-effectiveness of these regimens as induction therapy for MM patients ineligible for autologous stem cell transplantation (ASCT). An indirect comparison of VMP versus thalidomide plus MP (MPT) was also conducted using published results from the IFM 99-06 clinical trial for MPT (Facon et al, Lancet 2007). The goal of this study and the derived model was to assess the relative costs and outcomes from these two trials, recognizing the limitations imposed by using data derived from independent studies. Methods: A Markov model from the US payer's perspective was developed. Simulations were performed for hypothetical cohorts of newly diagnosed MM patients with an average age of 70 years at treatment initiation and who were not eligible for ASCT. The model includes seven health states representing periods of treatment response (stable disease/minimal response, partial response, or complete response), treatment-free interval, progressive disease, second-line treatment and death. Monthly transition probabilities were estimated from patient-level VISTA trial data for VMP and MP (with a data cut-off of June 15, 2007), and from the published phase lll IFM 99-06 trial for MPT. Costs included per-protocol drug and medical costs, treatment-related adverse events, second-line treatment, and resource utilization during treatment-free interval and progressive disease. Unit costs of medications and resources were obtained from published literature. All costs were adjusted to 2009 US dollars. State-specific utility estimates were derived from patient-level EQ-5D data from the VISTA trial using US-specific weights. Health outcomes were expressed in life-years (LYs) and quality-adjusted life-years (QALYs). Both cost and health outcomes were discounted at 3%. Incremental cost-effectiveness ratios (ICERs) were calculated for VMP versus MP, and VMP versus MPT, over a lifetime horizon (approximated by 20 years). One-way sensitivity analyses were conducted by running the model with upper and lower values of key parameters to assess the general robustness of model findings and identify key drivers. Results: Model base case results for the incremental cost-effectiveness of VMP relative to MP and MPT are shown in the Table. Comparison of the model's overall survival (OS) projections with the observed differences indicates a conservative approximation of the treatment differences for VMP. The estimated OS was 4.187 years with VMP versus 2.864 years with MP and versus 4.140 years with MPT over a lifetime horizon. Lifetime direct medical costs range from $57,864 for MP to $129,902 for MPT. The cost per LY and QALY gained with VMP compared with MP is $40,051 and $56,109, respectively. VMP is dominant (cost saving and better outcomes) compared with MPT, costing 17.7% less and providing slightly more QALYs on average. One-way sensitivity analyses suggest general robustness of model findings and the key drivers include VMP/MP hazard ratio from second-line treatment to death, and the MPT/MP hazard ratio for treatment discontinuation. Conclusions: In newly diagnosed MM patients ineligible for ASCT, VMP is projected to improve long-term health outcomes, offering a substantial survival benefit compared with MP. The incremental cost-effectiveness of VMP versus MP is within the generally accepted cost-effectiveness range of $50,000 to $100,000 per QALY, suggesting that VMP is cost-effective compared with MP in the United States. Within this cost-effectiveness model, compared with MPT, VMP is dominant, yielding lower costs and better health outcomes. Disclosures: Wang: Milllennium: Research Funding. Huang: Milllennium: Employment, Equity Ownership. Shi: Millennium Pharmaceuticals, Inc.: Employment. Duh: Milllennium: Consultancy, Research Funding. Chen: Milllennium: Research Funding. Chang: Milllennium: Research Funding. Korves: Milllennium: Research Funding. Dhawan: Johnson and Johnson Research Pharmaceuticals: Employment. Cakana: Johnson & Johnson: Employment, Equity Ownership. van de Velde: Johnson & Johnson: Employment, Equity Ownership. Esseltine: Milllennium: Employment, Equity Ownership. Garrison: Milllennium: Consultancy.

scholarly journals Selinexor Plus Pomalidomide and Low Dose Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1993-1993
Author(s):  
Christine I Chen ◽  
Heather J. Sutherland ◽  
Rami Kotb ◽  
Michael Sebag ◽  
Darrell J. White ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Board Of Directors ◽  
Nuclear Export ◽  
Research Funding ◽  
Low Dose ◽  
Published Data ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Introduction - The nuclear export protein exportin 1 (XPO1) is overexpressed in a wide variety of cancers including multiple myeloma (MM). Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates XPO1. Selinexor forces nuclear retention and reactivation of cell cycle regulators such as p53, IkB, and Rb. Pomalidomide/dexamethasone (Pd) is approved in relapsed/refractory MM (RRMM)with an overall response rate (ORR) of 30% and progression-free survival (PFS) rate of <4 months in patients (pts) having received a prior proteasome inhibitor (PI) and IMiD. Strategies to improve the ORR and PFS are needed. In murine MM models, the combination of selinexor with IMiDs shows synergistic anti-MM activity and good tolerability. Methods- Pts with RRMM who received ≥ 2 prior therapies including lenalidomide (len) and a PI were enrolled. Selinexor was evaluated in 2 different dosing schedules of once-weekly (QW, 60 or 80 mg) or twice-weekly (BIW, 60 or 80 mg), with pomalidomide (pom)3 or 4 mg PO daily, and dexamethasone (dex) 20 mg BIW or 40 mg QW. The primary objectives were to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, and preliminary efficacy of the combination of selinexor, pomalidomide, and low dose dex (SPd) in pts with RRMM. Results- As of July 20th2018, 34 pts (16 male / 18 female) have been enrolled. The median age is 61 years and patients received a median of 4 (range, 2 - 9) prior treatment regimens. Thirty-two patients were IMiD refractory (21 len, 11 pom/len). Six dose limiting toxicities (DLTs) were observed: G3 fatigue (60 mg BIW, pom 4 mg), G3 febrile neutropenia (FN) (60 mg BIW, pom 3 mg), G3 FN and G4 neutropenia (80 mg QW, pom 4), G3 thrombocytopenia (80 mg QW, pom 3 mg) and 4 missed doses in Cycle 1 due to symptomatic hyponatremia (80 mg BIW, pom 4 mg). Enrollment on selinexor 80 mg QW, pom 3 mg is ongoing. Common SPd treatment related adverse events included (all grades, grades 3/4): neutropenia (62%, 56%), thrombocytopenia (59%, 32%), anemia (53%, 29%), anorexia (56%, 0%), fatigue (50%, 9%), nausea (47%, 0% ). Thirty pts were evaluable for response, which is outlined in Table 1. Median PFS is 10.3 months with a median follow up of 9.4 months. Conclusions- Enrollment is ongoing to evaluate once weekly selinexor in combination with Pd , (SPd). This all-oral SPd combination has clinical activity with an ORR 55% in pom-naive pts with heavily pretreated MM compared to previously published data of 30% ORR for Pd alone. Similarly, the PFS on SPd is 10.3 months vs. <4 months for Pd alone. No unexpected adverse events were noted. Phase 1 dose escalation of the combination of SPd is ongoing to define the optimal RP2D. Disclosures Chen: Amgen: Honoraria. Sebag:Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees. White:Amgen, Celgene, Janssen, Takeda: Honoraria. Bensinger:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Speakers Bureau. Gasparetto:Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel; Janssen: Consultancy, Honoraria, Other: Travel; Takeda: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel, Research Funding. Leblanc:Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Schiller:Pharmacyclics: Research Funding; Celator/Jazz Pharmaceuticals: Research Funding. Lipe:Celgene: Consultancy. Shah:Karyopharm Therapeutics: Employment. Jeha:Karyopharm Therapeutics: Employment. Saint-Martin:Karyopharm Therapeutics: Employment. Kauffman:Karyopharm Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shacham:Karyopharm Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Bahlis:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

The Cost-Effectiveness of Bortezomib Plus Melphalan and Prednisone Versus Lenalidomide Plus Melphalan and Prednisone with Continuous Lenalidomide Maintenance Treatment for the Initial Treatment of Multiple Myeloma In the United States

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2563-2563 ◽  
Author(s):  
Si-Tien Wang ◽  
Hui Huang ◽  
Abbie Ba-Mancini ◽  
Hongliang Shi ◽  
Kristina Chen ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Health Outcomes ◽  
Incremental Cost ◽  
Survival Benefit ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Equity Ownership

Abstract Abstract 2563 Background: Results from the phase 3 VISTA trial demonstrated that bortezomib (Velcade®) plus melphalan and prednisone (VMP) has superior efficacy to MP alone in patients with newly diagnosed multiple myeloma (MM) ineligible for ASCT. In a similar patient population, the three-arm phase 3 MM-015 trial compared lenalidomide (Revlimid®) plus MP with or without continuous lenalidomide maintenance treatment after cycle 9 (MPR-R vs MPR) with MP alone. There was no difference in progression-free (PFS) or overall survival (OS) between patients who received MPR or MP during the 9-cycle induction period; MPR-R was associated with superior PFS vs MP during the R maintenance period. To assess the value of R in combination with MP followed by R maintenance therapy we indirectly estimated the incremental cost-effectiveness of VMP vs MPR-R as therapy for MM patients ineligible for ASCT. Methods: An Excel-based Markov model from the US payer's perspective was developed. Simulations were performed for hypothetical cohorts of newly diagnosed MM patients ineligible for ASCT with an average age of 70 years at treatment initiation. The model includes seven health states representing periods of treatment response (stable disease/minimal response, partial response, and complete response), treatment-free interval/maintenance treatment, progressive disease, second-line treatment, and death. Monthly transition probabilities were estimated from patient-level data for VISTA for VMP and MP (data cut-off June 15 2007; San Miguel et al NEJM 2008) and published results for MM-015 for MPR-R (data cut-off April 15 2009; Palumbo et al ASH 2009). As previously reported (Wang et al ASH 2009), costs included per-protocol drug and medical costs, treatment-related adverse event costs, second-line treatment costs, and resource utilization during the treatment-free interval and progressive disease; all costs were adjusted to 2010 US dollars. State-specific utility estimates were derived from patient-level EQ-5D data from the VISTA trial using US-specific weights. Health outcomes (as indicators of the effectiveness of therapy) were expressed in life years (LYs) and quality-adjusted LYs (QALYs). Costs and health outcomes were discounted at 3%. Incremental cost-effectiveness ratios (ICERs) were calculated for VMP vs MPR-R over a lifetime horizon (20 years). In the base case, the MPR-R vs MP hazard ratio (HR) for PFS was set to 0.499 and that for OS was set to 1, due to a lack of survival benefit with MPR-R vs MP observed in MM-015. One-way sensitivity analyses were conducted by running the model with upper and lower values of key parameters to assess the general robustness of model findings and identify key drivers. Results: Model base case results for the incremental cost-effectiveness of VMP relative to MPR-R are shown in the Table. Estimated OS was 4.187 years with VMP vs 3.409 years with MPR-R over a lifetime horizon. Lifetime direct medical costs were $119,102 with VMP vs $241,247 with MPR-R; the lifetime cost of R maintenance was $107,047. Thus, VMP appears associated with reduced costs and better outcomes vs MPR-R; VMP costs approximately 50% less than MPR-R and seems to provide slightly more QALYs (0.567) on average. One-way sensitivity analyses supported the general robustness of model findings and identified the MPR-R vs MP HR for OS as a key driver; only when this HR was set to ≤0.25 did MPR-R become cost-effective vs VMP at $100,000 per QALY. Conclusions: In newly diagnosed MM patients ineligible for ASCT, VMP appears to be associated with lower costs and better health outcomes vs MPR-R. From a cost-effectiveness perspective, R maintenance therapy therefore seems to have little benefit in this patient population. The current comparison was based on published results for MPR-R from MM-015 after a median follow-up of 9.4 months (vs 16.3 months for VMP vs MP in VISTA), at which time no survival benefit was observed for MPR-R vs MP. If longer follow-up in MM-015 indicates a survival benefit for MPR-R vs MP, a re-estimation of the incremental cost-effectiveness of VMP vs MPR-R using the present Markov model would be warranted; however, updated data (Palumbo et al EHA 2010) show no significant difference in OS between the MPR-R and MP arms at a median follow-up of 21 months. Disclosure: Wang: Millennium Pharmaceuticals: Consultancy, Research Funding. Huang:Millennium Pharmaceuticals, Inc: Employment. Ba-Mancini:Millennium Pharmaceuticals, Inc.: Employment. Shi:Millennium Pharmaceuticals, Inc: Employment. Chen:Millennium Pharmaceuticals: Consultancy, Research Funding. Korves:Millennium Pharmaceuticals, Inc: Research Funding. Dhawan:Johnson & Johnson: Employment, Equity Ownership. Cakana:Johnson & Johnson: Employment, Equity Ownership. van de Velde:Johnson & Johnson: Employment, Equity Ownership. Esseltine:Millennium Pharmaceuticals, Inc.: Employment; Johnson & Johnson: Equity Ownership. Duh:Millennium Pharmaceuticals, Inc: Consultancy, Research Funding.

Cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders in Singapore

2018 ◽  
Vol 41 (2) ◽  
pp. 391-398
Author(s):  
Monica Teng ◽  
Hui Jun Zhou ◽  
Liang Lin ◽  
Pang Hung Lim ◽  
Doreen Yeo ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Musculoskeletal Disorders ◽  
Cost Effective ◽  
Target Population ◽  
Quality Adjusted Life Year ◽  
Decision Analytic Model ◽  
Published Data ◽  
Total Knee ◽  
The Cost ◽  
Quality Adjusted Life

Abstract Background The study evaluated the cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders (MSDs) in Singapore. Methods A decision-analytic model was constructed to compare the cost-effectiveness of hydrotherapy to land-based therapy over 3 months from societal perspective. Target population comprised patients with low back pain (LBP), osteoarthritis (OA), rheumatoid arthritis (RA), total hip replacement (THR) and total knee replacement (TKR). Subgroup analyses were carried out to determine the cost-effectiveness of hydrotherapy in individual MSDs. Relative treatment effects were obtained through a systematic review of published data. Results Compared to land-based therapy, hydrotherapy was associated with an incremental cost-effectiveness ratio (ICER) of SGD 27 471 per quality-adjusted life-year (QALY) gained, which was below the willingness-to-pay threshold of SGD 70 000 per QALY (one gross domestic product per capita in Singapore in 2015). For the respective MSDs, hydrotherapy were dominant (more effective and less costly) in THR and TKR, cost-effective for LBP and RA, and not cost-effective for OA. Treatment adherence and cost of hydrotherapy were key drivers to the ICER values. Conclusions Hydrotherapy was a cost-effective rehabilitation compared to land-based therapy for a population with MSDs in Singapore. However, the benefit of hydrotherapy was not observed in patients with OA.

scholarly journals Comparative clinical effects and cost–effectiveness of maximum androgen blockade, docetaxel with androgen deprivation therapy and ADT alone for the treatment of mHSPC in China

2019 ◽  
Vol 8 (11) ◽  
pp. 865-877 ◽  
Author(s):  
Maobai Liu ◽  
Shuli Qu ◽  
Yanjun Liu ◽  
Xingxing Yao ◽  
Wei Jiang
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Androgen Deprivation Therapy ◽  
Cost Effective ◽  
Quality Adjusted Life Year ◽  
Incremental Cost Effectiveness Ratio ◽  
Clinical Effects ◽  
Cost Effectiveness Ratio ◽  
Quality Adjusted Life ◽  
Androgen Blockade

Aim: To compare the clinical effects and cost–effectiveness of maximum androgen blockade (MAB), docetaxel to androgen deprivation therapy (Doc-ADT) and ADT alone for the treatment of patients with metastatic hormone-sensitive prostate cancer in China. Methods: A network meta-analysis and a Markov model were adopted for effectiveness and economic evaluation. Results: The hazard ratios of overall survival and progression-free survival were 0.782 and 0.628 for Doc-ADT versus ADT alone; 0.897 and 0.824 for MAB versus ADT alone. Doc-ADT was cost-effective compared with MAB and ADT alone, with an incremental cost–effectiveness ratio of CNY 96,848 and CNY 67,758 per quality-adjusted life year, respectively. MAB was cost-effective compared with ADT alone, with an incremental cost–effectiveness ratio of CNY 137,487 per quality-adjusted life year. Conclusion: Doc-ADT is likely the optimal option from the perspective of both clinical outcomes and economic considerations.

Cost-Effectiveness of Primary Prophylaxis with Pegfilgrastim Versus Filgrastim in Non-Hodgkin’s Lymphoma Patients Receiving CHOP-21.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5166-5166 ◽  
Author(s):  
John Kim ◽  
Jennifer L. Malin ◽  
Quan V. Doan ◽  
Zhimei Liu ◽  
Robert W. Dubois ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Hodgkin’S Lymphoma ◽  
Primary Prophylaxis ◽  
Quality Adjusted Life Year ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact ◽  
Quality Adjusted Life

Abstract Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) starting in the first and continuing in subsequent chemotherapy cycles when the risk of febrile neutropenia (FN) is ≥20% is recommended in the 2006 ASCO and EORTC clinical guidelines. Although the daily G-CSF filgrastim (Neupogen®, Amgen Inc.) and the long-acting G-CSF pegfilgrastim (Neulasta®, Amgen Inc.) are both commonly used, in practice filgrastim is often administered for shorter-than-recommended courses, eg, 6 days, which has been shown to be associated with less clinical efficacy. The purpose of this study was to evaluate the cost-effectiveness of primary prophylaxis using pegfilgrastim versus 6-day filgrastim in patients with aggressive non-Hodgkin’s lymphoma (NHL) receiving CHOP-21. Without G-CSF support, CHOP-21 is associated with 17%-50% FN risk. We constructed a decision-analytic model from a payer perspective with a life-time study horizon. Outcomes were measured as incremental cost-effectiveness ratios (ICERs) including cost per FN event avoided, cost per life-year-gained (LYG), or cost per quality-adjusted-life-year (QALY) saved. Model inputs including FN risk, FN case-fatality, relative dose intensity (RDI) of chemotherapy, impact of RDI on survival, and utility scores were obtained from a comprehensive literature review. Drug and drug administration costs were obtained from Center for Medicare and Medicaid Services. Cost for FN-related hospitalizations and subsequent medical costs were obtained from the literature. NHL mortality rates and other-cause mortality were based on data from US Surveillance Epidemiology and End Results and National Vital Statistics Reports. Sensitivity analyses were conducted on key variables. Our model simulated 3 clinical scenarios: Scenario 1 included the impact of prophylaxis with pegfilgrastim or filgrastim on FN risk, Scenario 2 included the impact of a difference in FN risk on FN-related mortality, and Scenario 3 included a differential impact on RDI and long-term survival. Extrapolating from the results of a meta-analysis and observational studies, it was estimated that pegfilgrastim decreased the absolute risk of FN by 12% compared with 6-day filgrastim (13.1% versus 25.1%) for a baseline FN risk of approximately 27.9%. Our results showed that compared with 6-day filgrastim, pegfilgrastim was associated with an ICER of $2,133/FN event avoided in Scenario 1, $4,869/LYG or $5,476/QALY saved in Scenario 2, and $1,805/LYG or $2,029/QALY saved in Scenario 3 (Table 1). Key factors influencing ICER estimates included relative risk of FN, cost of pegfilgrastim and filgrastim, and baseline FN risk. Varying these variables within plausible ranges, the ICERs did not exceed $100,000/QALY saved, a commonly cited threshold for judging cost-effectiveness in oncology. Our study suggested that primary prophylaxis with pegfilgrastim is cost-effective compared with filgrastim used for 6 days in NHL patients receiving CHOP-21. Table 1: Cost-effectiveness of pegfilgrastim versus filgrastim Cost ($) Scenario 1 Scenario 2 (LY) Scenario 2 (QALY) Scenario 3 (LY) Scenario 3 (QALY) ICER, incremental cost-effectiveness ratio; LY, life-year; QALY, quality-adjusted life year; numbers may not match due to rounding errors Pegfilgrastim 15,608 13.1% 9.35 8.13 8.09 7.01 Filgrastim 15,352 25.1% 9.29 8.08 7.95 6.89 ICER --- $2,133 per FN event avoided $4,869/LY $5,476/QALY $1,805/LY $2,029/QALY

A Phase I/II Trial of the KSP Inhibitor ARRY-520 In Relapsed/Refractory Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1959-1959 ◽  
Author(s):  
Jatin J Shah ◽  
Jeffrey A. Zonder ◽  
Adam Cohen ◽  
Donna Weber ◽  
Sheeba Thomas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dose Escalation ◽  
Research Funding ◽  
Phase 1 ◽  
Single Agent ◽  
Clinical Activity ◽  
Employment Equity ◽  
Heavily Pretreated ◽  
Equity Ownership ◽  
Ksp Inhibitor

Abstract Abstract 1959 Background: Kinesin Spindle Protein (KSP) is required for cell cycle progression through mitosis. Inhibition of KSP induces mitotic arrest and cell death. ARRY-520 is a potent, selective KSP inhibitor. Cancers such as multiple myeloma (MM) which depend on the short-lived survival protein MCL-1 are highly sensitive to treatment with ARRY-520. ARRY-520 shows potent activity in preclinical MM models, providing a strong rationale for its clinical investigation in this disease. Methods: This Phase 1 study was designed to evaluate the safety and pharmacokinetics (PK) of ARRY-520 administered intravenously (IV) on Day 1 and Day 2 q 2 weeks without/with granulocyte-colony stimulating factor (G-CSF). Patients (pts) with relapsed/refractory (RR) MM with 2 prior lines of therapy (including both bortezomib and an immunomodulatory agent, unless ineligible for or refusing to receive this therapy) were eligible. Cohorts of at least 3 pts were enrolled in a classical 3 + 3 dose escalation design. Pts were treated for 2 cycles (4 weeks) to evaluate safety prior to dose escalation. Results: Twenty five pts have been treated to date, with a median age of 60 years (range 44–79) and a median of 5 prior regimens (range 2–16). All pts received prior bortezomib or carfilzomib, 21 pts received prior lenalidomide, 17 pts prior thalidomide, and 18 pts had a prior stem cell transplant. Pts received ARRY-520 without G-CSF at 1 mg/m2/day (n = 3), and at 1.25 mg/m2/day (n = 7, 6 evaluable). A dose-limiting toxicity (DLT) of Grade 4 neutropenia was observed at 1.25 mg/m2/day, and this was considered the maximum tolerated dose (MTD) without G-CSF. As neutropenia was the DLT, dose escalation with prophylactic G-CSF support was initiated, at doses of 1.5 mg/m2/day (n = 7, 6 evaluable), 2.0 mg/m2/day (n = 6) and 2.25 mg/m2/day (n = 2) with G-CSF. Both the 2.0 mg/m2/day and 2.25 mg/m2/day dose levels were determined to be non-tolerated, with DLTs of febrile neutropenia (FN) (2 pts at 2.0 mg/m2/day and both pts at 2.25 mg/m2/day) and Grade 3 mucositis (both pts at 2.25 mg/m2/day). One out of 6 evaluable pts at 1.5 mg/m2/day also developed a DLT of FN. In an attempt to optimize the Phase 2 dose, an intermediate dose level of 1.75 mg/m2/day with G-CSF is currently being evaluated. The most commonly reported treatment-related adverse events (AEs) include those observed with other KSP inhibitors, such as hematological AEs (thrombocytopenia, neutropenia, anemia, leukopenia), fatigue, mucositis and other gastro-intestinal AEs. Pts displayed linear PK, a low clearance and a moderate volume of distribution, with moderate-to-high inter-individual variability in PK parameters. The median terminal elimination half life is 65 hours. The preliminary efficacy signal as a single agent is encouraging with 2 partial responses (PR) observed to date per IMWG and EBMT criteria in a heavily pretreated population (23 evaluable pts). A bortezomib-refractory pt with 8 prior lines of therapy, including a tandem transplant, treated at 1 mg/m2/day of ARRY-520 obtained a PR after Cycle 6, with urine protein and kappa light chain levels continuing to decline over time. He remains on-study after 15 months of ARRY-520 treatment. A pt with 2 prior lines of therapy, including prior carfilzomib, has obtained a PR after Cycle 8 at 2 mg/m2/day of ARRY-520, and she is currently ongoing after 4.5 months on therapy. Fifteen pts had a best response of stable disease (SD), including 1 pt with a thus far unconfirmed minimal response, and 6 had progressive disease. A total of 10 pts (43%) achieved a PR or SD lasting > 12 weeks. Several additional pts have shown other evidence of clinical activity, with decrease in paraproteins, increase in hemoglobin levels and regression of plasmacytomas. The median number of cycles is 4 (range 1–28+). Treatment activity has not correlated with any baseline characteristics or disease parameters to date. Conclusions: : The selective KSP inhibitor ARRY-520 has been well tolerated, and shows promising signs of single agent clinical activity in heavily pretreated pts with RR MM. Prophylactic G-CSF has enabled higher doses to be tolerated. No cardiovascular or liver enzyme toxicity has been reported. Enrollment is ongoing at 1.75 mg/m2/day with G-CSF support, and a planned Phase 2 part of the study will be initiated as soon as the MTD is determined. Complete Phase 1 data will be disclosed at the time of the meeting. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding. Off Label Use: Revlimid (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. Zonder:Millennium: Consultancy, Myeloma and Amyloidosis Patient Day Symposium – Corporate support from multiple sponsors for a one-day educational event, Research Funding; Celgene:; Novartis:; Proteolix: . Weber:novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; celgene- none for at least 2 years: Honoraria; millenium-none for 2 years: Honoraria; celgene, Millenium, Merck: Research Funding. Wang:Celgene: Research Funding; Onyx: Research Funding; Millenium: Research Funding; Novartis: Research Funding. Kaufman:Celgene: Consultancy, Honoraria, Research Funding; Millenium: Consultancy, Honoraria; Merck: Research Funding; Genzyme: Consultancy. Walker:Array Biopharma: Employment, Equity Ownership. Freeman:Array Biopharma: Employment, Equity Ownership. Rush:Array Biopharma: Employment, Equity Ownership. Ptaszynski:Array Biopharma: Consultancy. Lonial:Millennium, Celgene, Bristol-Myers Squibb, Novartis, Onyx: Advisory Board, Consultancy; Millennium, Celgene, Novartis, Onyx, Bristol-Myers Squibb: Research Funding.

Population Pharmacokinetic and Pharmacodynamic Modeling of an Anti–Interleukin-6 Chimeric Monoclonal Antibody, Siltuximab (CNTO 328), in Patients with B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1365-1365 ◽  
Author(s):  
Lanyi Xie ◽  
Lilian Y Li ◽  
Razelle Kurzrock ◽  
Frits van Rhee ◽  
Xiang Qin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
B Cell ◽  
Treatment Period ◽  
Research Funding ◽  
Castleman’S Disease ◽  
Hodgkin's Lymphoma ◽  
Employment Equity ◽  
Dosing Regimens ◽  
Equity Ownership

Abstract Abstract 1365 Introduction Siltuximab (CNTO 328) is a chimeric, murine-human, monoclonal antibody that specifically binds human interleukin (IL)-6 with high affinity. C-reactive protein (CRP) can be a pharmacodynamic (PD) marker of IL-6 bioactivity, i.e., reductions in CRP suggest inhibition of systemic IL-6. A population mechanistic pharmacokinetic (PK)/PD model was developed to describe the relationship between siltuximab serum concentrations and CRP suppression in patients with B-cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), or Castleman's disease (CD). Simulation was used to support the dose selection in the CD registration study and future clinical studies. Methods PK/PD data were obtained from a phase 1 clinical study examining multiple dosing regimens of siltuximab administered intravenously in patients with NHL, MM, or CD. Dosing regimens included siltuximab 2.8, 5.5, or 11 mg/kg every 2 weeks; 11 mg/kg every 3 weeks; or 5.5 mg/kg every week. Serial samples to determine serum concentration of siltuximab and serial CRP samples were collected following the first dose. NONMEM 7 was used to simultaneously fit a two-compartment PK model and an inhibitory indirect-response PD model to the observed data. Simulation of 1000 replications was then used to identify siltuximab dosage regimens that would maintain CRP suppression below the lower limit of quantification (LLOQ) of 1 mg/L. Results The mechanistic PK/PD model was able to describe the serum siltuximab and CRP concentration-time profiles. Volume of distribution and systemic clearance rate constant of siltuximab were estimated at 68.42 mL/kg and 0.0584/day, respectively. The PD parameter estimates (Kin and Kout of CRP) were 5.03 mg/L/day and 0.457/day, respectively, and were similar between the three disease types in this study. IC50was estimated at 9.73 μg/mL and was also similar between disease types. For all disease types, simulations showed that siltuximab 11 mg/kg every 3 weeks or 15 mg/kg every 4 weeks after the second dose would reduce serum CRP to below the LLOQ throughout the entire treatment period. However, lower dose intensive schedules, including a dose of 5.5 mg/kg every 2 weeks, would not reduce CRP to below the LLOQ at any time point during the treatment period. Conclusion The population PK/PD modeling and simulation support using a siltuximab dose of 11 mg/kg every 3 weeks or 15 mg/kg every 4 weeks in future clinical development studies. This dosing recommendation is supported by the observed efficacy dose-response relationship in patients with CD (J Clin Oncol 2010;28:3701–8). Disclosures: Xie: Johnson & Johnson: Employment, Equity Ownership. Li:Johnson & Johnson: Employment, Equity Ownership. Kurzrock:Johnson & Johnson: Honoraria, Research Funding. van Rhee:Johnson & Johnson: Research Funding. Qin:Johnson & Johnson: Employment, Equity Ownership. Reddy:Johnson & Johnson: Employment, Equity Ownership. Qi:Johnson & Johnson: Employment, Equity Ownership. Davis:Johnson & Johnson: Employment, Equity Ownership. Zhou:Johnson & Johnson: Employment, Equity Ownership. Puchalski:Johnson & Johnson: Employment, Equity Ownership.

Relationship Between Lenalidomide Dose Modification and Duration Of Treatment In Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2944-2944
Author(s):  
Kathy Lang ◽  
Gary Binder ◽  
Iris Lin ◽  
Dejan Milentijevic ◽  
Huan Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dose Reduction ◽  
Research Funding ◽  
Duration Of Treatment ◽  
Employment Equity ◽  
Medical Claims ◽  
Dose Modification ◽  
Equity Ownership ◽  
Dose Change ◽  
Dose Reductions

Abstract Introduction A number of studies have shown clinical benefits for multiple myeloma (MM) patients who continue to stay on therapy with lenalidomide (LEN), including progression-free survival (PFS) and overall survival (OS) (Palumbo A, et al. NEJM. 2013, McCarthy P, et al. NEJM. 2013, Boccadoro. JCO. 2013). Dose modification is one factor used by physicians to achieve sustained duration of treatment (DOT), particularly to manage toxicities and/or pursue a continuous therapy regimen; in a clinical trial of LEN in newly diagnosed MM (NDMM) patients (pts) followed-up for a median of 30 mos, 42% of pts experienced a dose reduction (Palumbo A, et al. NEJM. 2012). This analysis evaluated whether there is supporting evidence, in a real-world setting, for physicians using LEN dose modification to achieve a longer time on therapy. Objective Medical claims analysis was performed to evaluate the relationship between lenalidomide (LEN), dose modification and DOT among patients with NDMM. Methods A retrospective cohort analysis was conducted using a claims database from a large US payer, covering approximately 14 million commercially insured and Medicare advantage members. Patients with at least two outpatient or one inpatient medical claims associated with a diagnosis of MM (ICD-9-CM code: 203.0x) between Jan 1, 2008 and Oct 31, 2012 were extracted from the database. Index date was defined as the date of the first diagnosis of MM. A minimum of 12 months pre-index and 6 months post-index enrollment with no MM treatment was required to define the NDMM patient population. To avoid DOT limitations imposed by fixed-length induction therapy, only pts without claims for stem cell transplant (SCT) were evaluated. DOT was compared among the group treated with LEN who had dose modification (increase or decrease in number of mg per day) relative to the group with no dose modification. Results Among the 236 pts meeting the inclusion criteria, 69 (29%) pts had LEN dose reductions, 15 (6%) had dose increases, and 152 (64%) had no dose change. DOT in pts without a dose change was 7.33 months ± 7.62 (mean ± SD), while pts who had a dose reduction had significantly longer DOT of 14.63 months ± 10.47 (p<0.01). Of the 69 pts with dose reductions, DOT before dose reduction was 5.18 months ± 4.82 compared with 9.46 months ± 10.26 after dose reduction (p<0.01, paired). The subset of pts who were still on LEN therapy at the end of the data window (N=27) showed a similar association between dose reduction and DOT, with DOT of 20.29 months ± 11.62 and 11.99 months ± 9.29 in dose reduction and non-dose reduction subgroups (p<0.01), respectively. Conclusion NDMM pts who had dose reductions of LEN had twice the duration of therapy compared with pts without dose reductions. This analysis suggests that dose modification of MM treatment may be an effective tool to help pts achieve the benefits associated with longer time on therapy. Future clinical studies are needed to determine the best approaches to dose adjustment to improve disease control. Disclosures: Lang: Celgene: Research Funding. Off Label Use: Lenalidomide is a thalidomide analog indicated for the treatment of multiple myeloma, in combination with dexamethasone, in patients who have received at least one prior therapy. Binder:Celgene: Employment, Equity Ownership. Lin:Celgene: Research Funding. Milentijevic:Celgene: Consultancy. Huang:Celgene: Research Funding. Nagarwala:Celgene: Employment, Equity Ownership. Harwin:Celgene: Honoraria.

Patterns of Total Costs of Care for Newly Diagnosed Multiple Myeloma (MM) Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2656-2656
Author(s):  
Steven R. Arikian ◽  
Dejan Milentijevic ◽  
Gary Binder ◽  
Mara Silvia Monzini ◽  
X Henry Hu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Direct Costs ◽  
Drug Costs ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Monthly Total ◽  
Equity Ownership ◽  
The Cost ◽  
Over Time

Abstract Introduction: As clinical evidence has mounted in support of novel agents and longer treatment (Tx) durations for patients (pts) with newly diagnosed multiple myeloma (NDMM), questions have arisen regarding the economic impact of extending time to progression (TTP) in these pts, and the cost consequences once pts relapse and move to a second line of Tx. Previous analysis showed that relapsed myeloma pts incurred higher monthly costs once they advanced to later lines of Tx (Gaultney, 2013). There is limited information on the cost patterns of MM pts before and after their first relapse. A claims analysis was performed to evaluate the patterns of total direct costs of care, from Tx initiation until progression, for NDMM patients and for newly relapsed patients treated with novel agents, utilizing time to next therapy (TTNT) as a proxy measure for progression. Methods: A retrospective study was conducted using a large US medical and pharmacy claims database, covering > 25 million lives annually. NDMM patients were identified with at least 2 outpatient claims or 1 inpatient medical claim associated with a diagnosis of MM (ICD-9-CM] code 203.0X), with the first such claim used to define the index date. Inclusion criteria required a minimum of 12 months' pre-index enrollment and 6 months' post-index continuous enrollment between 2006 and 2012. Pts with claims for stem cell transplantation (SCT) were excluded, to avoid confounding results from various factors based on timing, costs, and site of care of SCT. The analysis focused on NDMM and relapsed MM pts receiving lenalidomide (LEN)- or bortezomib (BORT)- based Tx, where complete claim history was available from Tx onset to initiation of subsequent Tx. Using methods similar to those described by Gaultney, patients' average monthly costs were determined, including medical (inpatient, ambulatory, and emergency room) and pharmacy (index and other drugs) costs, and total cost patterns over quarterly time periods were calculated. Average Charlson comorbidity scores were determined to compare baseline measures between pt groups. Results: 897 NDMM pts and 280 relapsed MM pts were identified with complete data through initiation of subsequent Tx. Monthly total direct costs for NDMM pts were $15,400 in the first 3 months (mos) of Tx, and declined each quarter, reaching approximately $5,000/mo at 18+ mos. At relapse, monthly costs increased to over $12,000 for the first 3 mos and followed a quarterly pattern of reduction similar to that seen for NDMM pts (Fig 1). Quarterly cost reduction patterns were consistent for patients treated with LEN or BORT for both NDMM and relapsed pts. Pts' total monthly NDMM costs over the full TTNT period averaged $8,942 with LEN vs. $11,139 for BORT (due to 54% higher monthly medical costs for BORT), while monthly drug costs were nearly identical (Table 1). The baseline Charlson comorbidity index was similar between Tx groups in both lines of Tx. Figure 1: Direct monthly costs (medical and pharmacy) for LEN- and BORT-based treatments Figure 1:. Direct monthly costs (medical and pharmacy) for LEN- and BORT-based treatments Table 1: Direct monthly costs for NDMM pts Table 1 Table 1. Conclusions: For a population of NDMM pts receiving either LEN- or BORT-based Tx without SCT, followed until TTNT, total direct monthly costs per pt declined steadily over time, decreasing by 68% from the initial quarter to the period post 18 mos. Costs spiked when pts began 2nd-line therapy, then followed a similar pattern of decline over time. This pattern may suggest that further extending the TTP for NDMM pts may also yield economic benefits for each month extended before relapse. Patterns of cost decline were similar between the LEN and BORT groups, for NDMM and for relapsed patients, although mean monthly total costs were lower for NDMM pts receiving LEN-based Tx due to lower medical costs and similar drug costs. Disclosures Arikian: Genesis Research: Consultancy. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma patients . Milentijevic:Celgene Corporation: Consultancy. Binder:Celgene Corporation: Employment, Equity Ownership. Monzini:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment. Nagarwala:Celgene Corporation: Employment. Hussein:Celgene Corporation: Employment. Corvino:Genesis Research LLC: Consultancy. Surinach:Genesis Research LLC: Consultancy. Usmani:Celgene Corporation: Consultancy, Honoraria, Research Funding; Millennium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Array BioPharma: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding.

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