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

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.

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

Blood ◽

10.1182/blood.v114.22.1379.1379 ◽

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.

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Clinical Outcomes of Patients with Newly Diagnosed Multiple Myeloma Receiving Triplet Therapy in the Connect MM® Disease Registry

Blood ◽

10.1182/blood.v126.23.4229.4229 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4229-4229

Author(s):

Jatin J. Shah ◽

Rafat Abonour ◽

Mohit Narang ◽

Jayesh Mehta ◽

Howard R. Terebelo ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Risk Of Death ◽

Equity Ownership ◽

Triplet Regimen

Abstract Introduction: Triplet therapies are used for treatment (Tx) of both transplant-eligible and -ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Actual patterns and outcomes of Tx are not fully understood. Connect MM® is the first and largest multicenter, US-based, prospective observational cohort study designed to characterize Tx patterns and outcomes for pts with NDMM. This analysis describes demographic and disease characteristics of pts who received triplet Tx as an induction regimen and for whom transplant was or was not intended. The analysis explores the relationship of these factors with overall survival (OS) and other efficacy endpoints. Patients and Methods: Pts aged ≥ 18 y with NDMM within 60 days of diagnosis were eligible for enrollment regardless of disease severity, medical history, or comorbidities. Data including transplant intent (yes/no) was collected at baseline; follow-up data was collected quarterly thereafter. Based on the initial intent, 2 groups were identified: patients with intent to transplant who received transplant (TT) and pts with no intent to transplant who did not receive a transplant (NT). Triplet Tx was defined as the combination of ≥ 3 concurrent therapeutic agents in the first course of Tx (within 56 days of study entry). KM analysis adjusted for age was conducted for OS. Because decisions on use of transplant and triplet therapy are influenced by multiple factors, a multivariable Cox regression analysis was performed to evaluate the contribution of the triplet therapy (yes/no) to OS and was adjusted for other variables, including age, comorbidities, and ISS staging. Results: Between September 2009 and December 2011, 1493 pts were enrolled. This analysis was on 1436 pts: 650 pts with transplant intent and 786 pts without transplant intent. The data cutoff date was November 30, 2014, and the median follow-up for overall survival (OS) was 33.8 mos. Of pts with transplant intent, 451 (69%) received transplant (TT) and 199 (31%) did not. Of pts without transplant intent, 62 (8%) received transplant and 724 (92%) did not (NT). The abstract focuses on TT and NT groups only. NT pts tended to be older and have more advanced ISS staging and higher β2-microglobulin levels than TT pts (Table). The most common triplet regimen given during the first course treatment (within 56 days) was lenalidomide, bortezomib, and dexamethasone (RVd). RVd was administered to 34% of the NT pts (76/225) and 59% of the TT pts (152/257). The most common non-triplet regimen was bortezomib and dexamethasone (Vd), which was given to 31% of NT pts (156/499) and 38% of TT pts (73/194). Within the NT group, pts given triplet Tx had a lower risk of death than those who did not receive triplet Tx (P = .0013). The multivariable analysis found triplet Tx to be associated with a 36% reduced risk of death (hazard ratio [HR] = 0.64 [95% CI, 0.50-0.82]; P = .001). ISS disease stage (HR = 1.43 [95% CI, 1.21-1.69]; P < .001) and history of diabetes (HR = 1.38 [95% CI, 1.08-1.78]; P = .012) were negative prognostic factors for OS. Within the TT group, pts who received triplet Tx did not attain an OS benefit (P = .8993), and no baseline characteristics were significantly associated with OS. These results may be limited by other factors not considered that may have influenced physicians' choice of treatment, including the use of maintenance therapy and a short follow-up period of 33.8 months. Conclusions: Triplet Tx as a first regimen is associated with longer OS in pts without transplant intent who did not receive a transplant. RVd and Vd were the most common first Tx regimens, respectively. Continued follow-up of these pts and enrollment of an additional cohort will provide additional data with mature follow-up. Table 1. Table 1. Disclosures Shah: Bristol-Myers Squibb: Research Funding; Array: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Research Funding, Speakers Bureau. Narang:Celgene: Speakers Bureau. Mehta:Celgene Corporation: Speakers Bureau. Terebelo:Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacylics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gasparetto:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Honoraria, Other: Export Board Committee, Speakers Bureau. Toomey:Celgene: Consultancy. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Srinivasan:Celgene Corporation: Employment, Equity Ownership. Larkins:Celgene Corporation: Employment, Equity Ownership. Nagarwala:Celgene Corporation: Employment, Equity Ownership. Rifkin:Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Nilotinib Versus Imatinib in Patients (pts) with Newly Diagnosed Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENESTnd 36-Month (mo) Follow-up

Blood ◽

10.1182/blood.v118.21.452.452 ◽

2011 ◽

Vol 118 (21) ◽

pp. 452-452 ◽

Cited By ~ 9

Author(s):

Giuseppe Saglio ◽

Philipp D. LeCoutre ◽

Ricardo Pasquini ◽

Saengsuree Jootar ◽

Hirohisa Nakamae ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Philadelphia Chromosome ◽

Safety Data ◽

Molecular Response ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Abstract Abstract 452FN2 Background: In ENESTnd, pts treated with nilotinib demonstrated higher and faster rates of major molecular response (MMR, ≤ 0.1% BCR-ABLIS), deeper molecular response (MR4, ≤ 0.01%IS and MR4.5, ≤ 0.0032%IS), and complete cytogenetic responses (CCyR) along with significantly lower rates of progression to AP/BC and fewer CML-related deaths compared with imatinib by 12 and 24 mo. Here, we report data with a minimum follow-up of 24 mo; however, efficacy and safety data based on considerably longer follow-up of ≥ 36 mo will be presented. As demonstrated in IRIS and other imatinib trials, most pts who progress on imatinib do so within the first 3 years of therapy. Thus, this 36-mo update of ENESTnd will be important to further verify the benefits of nilotinib in newly-diagnosed pts. Methods: 846 adult pts with newly-diagnosed Ph+ CML-CP were randomized to nilotinib 300 mg twice daily (BID) (n = 282), nilotinib 400 mg BID (n = 281), or imatinib 400 mg once daily (QD) (n = 283). MMR, MR4, MR4.5, time to progression to AP/BC on treatment, progression-free survival (PFS) on treatment, and overall survival (OS) were evaluated. Results: By 24 mo, both doses of nilotinib demonstrated significantly higher rates of MMR, MR4, and MR4.5 vs imatinib (Table). Nilotinib-treated pts achieved median BCR-ABLIS levels of 0.09% (300 mg BID) and 0.10% (400 mg BID) by 12 mo, while this level of reduction was not observed before 24 mo on imatinib. More pts with CCyR achieved MMR at 12 and 24 mo with either dose of nilotinib vs imatinib (Table). Regardless of Sokal risk, rates of MMR and MR4.5 were higher for nilotinib at both doses vs imatinib (Table). Progression to AP/BC (excluding clonal evolution [CE]) on treatment was significantly lower for nilotinib vs imatinib (2 pts and 3 pts with nilotinib 300 mg BID [P = .0059] and 400 mg BID [P =.0196]), respectively vs 12 pts with imatinib). After achieving CCyR, 4 pts treated with imatinib progressed to AP/BC and 2 pts treated with nilotinib 400 mg BID progressed after achieving both CCyR and MMR (1 also achieved MR4). No pt who achieved MR4.5 progressed at any time. All but 1 pt who progressed to AP/BC on treatment were in the intermediate and high Sokal risk groups; 1 pt treated with nilotinib 400 mg BID progressed in the low Sokal risk group who had an E255V mutation at progression. When considering progression events of pts after discontinuation of treatment, an additional 7, 2, and 6 events (excluding CE) were observed with nilotinib 300 mg BID, nilotinib 400 mg BID and imatinib, respectively. Twice as many pts had emergent mutations on imatinib (n = 20) vs nilotinib (n = 10 on 300 mg BID; n = 8 on 400 mg BID). At 24 mo, OS remained similar in all groups, but there were fewer CML-related deaths in both nilotinib 300 mg BID (5 pts) and nilotinib 400 mg BID (3 pts) arms vs imatinib (10 pts). Both drugs were well tolerated and few new adverse events (AEs) and lab abnormalities were observed between 12- and 24-mo of follow-up. Nilotinib 300 mg BID had the fewest discontinuations due to AEs/lab abnormalities (9% vs 13% and 10% with nilotinib 400 mg BID and imatinib, respectively). Conclusions: With a minimum follow-up of 24 mo, nilotinib continued to demonstrate superiority vs imatinib with faster and deeper molecular responses and a significantly decreased risk of progression. These data support the use of nilotinib as a standard of care option in newly-diagnosed adult pts with Ph+ CML-CP. Disclosures: Saglio: Novartis Pharmaceutical: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Pfizer: Consultancy. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. LeCoutre:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria. Pasquini:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Nakamae:Novartis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau. Flinn:nOVARTIS: Research Funding. Hochhaus:Novartis Pharmaceutical: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding. Hughes:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Larson:Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding. Hoenekopp:Novartis Pharmaceutical: Employment, Equity Ownership. Gallagher:Novartis: Employment. Yu:Novartis: Employment, Equity Ownership. Blakesley:Novartis Pharmaceutical: Employment. Kim:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Novartis: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; BMS: Research Funding.

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

Blood ◽

10.1182/blood.v122.21.5604.5604 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5604-5604 ◽

Cited By ~ 1

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.

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Quality-Adjusted Survival for Low-Dose Cytarabine (LDAC) Versus Glasdegib+LDAC Among Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Not Candidates for Intensive Chemotherapy: A Q-TWiST Analysis

Blood ◽

10.1182/blood-2019-126672 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2610-2610 ◽

Cited By ~ 1

Author(s):

Youngmin Kwon ◽

Timothy J Bell ◽

Caitlyn Solem ◽

Joseph C Cappelleri ◽

Courtney Johnson ◽

...

Keyword(s):

Adverse Events ◽

Myeloid Leukemia ◽

Research Funding ◽

Newly Diagnosed ◽

Employment Equity ◽

Equity Ownership ◽

Relative Gains ◽

Mean Time ◽

Low Dose Cytarabine

Introduction: The efficacy and safety of glasdegib (a selective oral inhibitor of hedgehog signaling pathway) in combination with low-dose cytarabine (LDAC) was evaluated in a randomized, phase 2 trial of newly diagnosed acute myeloid leukemia (AML) patients (BRIGHT AML 1003; NCT01546038). Patients receiving glasdegib+LDAC experienced statistically significant and meaningful gains in overall survival (OS) compared with patients receiving LDAC alone (median OS [95% CI]): 8.3 months [4.7-12.2] vs 4.3 months [1.9-5.7]). This analysis examined whether quality-adjusted survival improvements were similarly observed using a quality-adjusted time without symptoms of disease progression or toxicities (Q-TWiST) approach to evaluate possible trade-offs between time with adverse events (toxicities), time in relapse/progression (i.e., with symptoms of disease), and 'good' survival (i.e., time without toxicities or symptoms of progression [TWiST]) when comparing regimens. Methods: OS in BRIGHT AML 1003 data, restricted to a follow-up of 20 months, was partitioned into time with toxicity (TOX: grade 3+ adverse events prior to progression), TWiST, and time post-progression (REL). Progression was defined as treatment discontinuation due to insufficient clinical response or death; patients who discontinued for other reasons (including adverse events) were censored at the date of discontinuation unless death occurred within 28 days of discontinuation. Q-TWiST was calculated by multiplying restricted mean time in each state by respective utilities (U) and then summing up the utility-adjusted time. Base case analysis used U(TOX)=U(REL)=0.5 and U(TWiST)=1.0; threshold analyses were performed varying U(TOX) and U(REL) jointly each from 0 to 1. Relative gains in Q-TWiST (i.e., Q-TWiST difference (combination vs LDAC) / OS in LDAC arm) of ≥15% were considered clearly clinically meaningful per the clinical literature. Sensitivity analysis varied the length of follow-up and AE definitions; subgroup analyses were also performed. 95% confidence intervals were obtained using the bootstrap procedure. Results: At 20 months of follow-up, the survival rate for glasdegib+LDAC and LDAC arm was 28.2% and 7.9%, respectively. Glasdegib+LDAC patients (n=78) compared with LDAC patients (n=38) had significantly longer mean time in TWiST (+3.4 [95% confidence interval: 1.8, 5.2] months) and TOX (+0.8 [0.1, 1.6] months), and longer but non-significant REL (+0.3 [-1.9, 2.3] months). Q-TWiST was 4.0 [2.1, 5.8] months longer for glasdegib+LDAC, translating into a 75% relative improvement in quality-adjusted survival relative to LDAC alone. In threshold analyses, absolute and relative Q-TWiST gains ranged from 3.5 to 4.5 months and 66% to 85%, respectively (Table 1). They exceeded the clinically meaningful threshold for gains in Q-TWiST and were statistically significant across all combinations of U(TOX) and U(REL). Results were robust to length of follow-up 6 to 24 month and remained significant when including all adverse events regardless of grade. Discussions/Conclusions: Glasdegib+LDAC is an add-on therapy that has demonstrated significant survival benefits for newly diagnosed AML patients who are unable to receive intensive chemotherapy. While patients can experience a longer time with toxicities from receiving glasdegib+LDAC (as expected since it is given as an add-on therapy), the trade-off can still be favorable as the treatment provides added time spent in 'good' health (i.e., a significantly longer time in TWiST). In the BRIGHT AML 1003 cohort, the relative gains in OS greatly exceeded previously established thresholds for being clearly clinically meaningful, which suggests that the benefits of glasdegib+LDAC vs LDAC alone outweigh the risks. Table 1 Disclosures Kwon: Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bell:Pfizer Inc.: Employment, Equity Ownership. Solem:Pharmerit International: Employment; Pfizer Inc.: Research Funding. Cappelleri:Pfizer: Employment, Equity Ownership. Johnson:Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bhattacharyya:Pfizer Inc: Employment, Equity Ownership. Hoang:Pfizer Inc.: Employment, Equity Ownership. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; BiolineRx: Consultancy; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

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Bosutinib Vs Imatinib for Newly Diagnosed Chronic Myeloid Leukemia (CML) in the BFORE Trial: 18 Month Follow-up

Blood ◽

10.1182/blood.v130.suppl_1.896.896 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 896-896

Author(s):

Carlo Gambacorti-Passerini ◽

Michael W. Deininger ◽

Michael J. Mauro ◽

Charles Chuah ◽

Dong-Wook Kim ◽

...

Keyword(s):

Board Of Directors ◽

Primary Endpoint ◽

Cumulative Incidence ◽

Research Funding ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership ◽

Grade 3

Abstract Introduction: Bosutinib is a potent SRC/ABL tyrosine kinase inhibitor approved for treatment of adults with CML resistant or intolerant to prior therapy. Here we compare the efficacy and safety of first-line bosutinib versus imatinib in patients with chronic phase (CP) CML enrolled in BFORE after ≥18 months of follow-up. Methods: BFORE (NCT02130557) is an ongoing, multinational, open label phase 3 study that randomized 536 patients 1:1 to 400 mg QD bosutinib (n=268) or 400 mg QD imatinib (n=268 [3 not treated]). The prespecified primary endpoint was major molecular response (MMR) rate at 12 months in the modified intent-to-treat (mITT) population, defined as Philadelphia chromosome‒positive (Ph+) patients with e13a2/e14a2 transcripts, and excluding Ph- patients and those with unknown Ph status and/or BCR-ABL transcript type (mITT: BOS, n=246; IM, n=241). Efficacy results refer to the mITT population unless otherwise noted. Results: MMR rate was higher with bosutinib versus imatinib at 18 months (56.9% vs 47.7%; P=0.042). Among all randomized patients (ITT) 18-month MMR rates were higher for bosutinib (56.7% vs 46.6%; P <0.02). Earlier analyses (Table) showed complete cytogenetic response (CCyR) rate by 12 months (77.2% vs 66.4%; P=0.0075) was significantly higher with bosutinib versus imatinib. Rates of BCR-ABL1 transcript ratio ≤10% (International Scale) at 3 months (75.2% vs 57.3%), as well as MR4 at 12 months (20.7% vs 12.0%) and MR4.5 at 12 months (8.1% vs 3.3%), were all higher with bosutinib versus imatinib (all P <0.025). By comparison at 18 months, rates of MR4 (24.4% vs 18.3%) and MR4.5 (11.4% vs 7.1%) were consistent with this trend. Also after ≥18 months follow-up, time to MMR (hazard ratio=1.36, based on cumulative incidence; P=0.0079) and time to CCyR (hazard ratio=1.33; P=0.0049) were shorter for bosutinib (Figure). Cumulative incidence of transformation to accelerated/blast phase disease at 18 months was 2.0% and 2.9% for bosutinb and imatinib, respectively, of which 2 bosutinib and 4 imatinib patients discontinued treatment due to transformation. Additional treatment discontinuations due to suboptimal response/treatment failure occurred in 11 (4.1%) and 35 (13.2%) of bosutinib and imatinib patients, respectively. Dose increases happened in 20% of bosutinib-treated and 31% of imatinib-treated pts There were 2 deaths and 9 deaths in the bosutinib and imatinib arms, respectively. One patient taking bosutinib died within 28 days of last dose, while 4 patients taking imatinib died with that period from last dose. Overall survival at 18 months was 99.6% vs. 96.6% for bosutinib and imatinib groups, respectively. Grade ≥3 diarrhea (8.2% vs 0.8%) and increased alanine (20.9% vs 1.5%) and aspartate (10.1% vs 1.9%) aminotransferase levels were more frequent with bosutinib. Cardiovascular, peripheral vascular, and cerebrovascular events were infrequent in both arms (3.4%, 1.9%, and 0.4% bosutinib vs 0.0%, 1.1%, and 0.8% imatinib; grade ≥3: 1.5%, 0%, and 0.4% vs 0%, 0%, and 0.4%). There were no deaths in the bosutinib arm and 1 death in the imatinib arm due to treatment-emergent vascular events. Treatment discontinuations due to drug-related toxicity occurred in 15.3% and 9.4% of bosutinib and imatinib patients, respectively. Conclusion: After 18 months of follow-up,the MMR benefit seen with bosutinib over imatinib was sustained. These results are in line with observations at 12 months where patients taking bosutinib had significantly higher response rates (primary endpoint) and achieved responses sooner than those on imatinib. Safety data were consistent with the known safety profiles. These results suggest that bosutinib may be an important treatment option for patients with newly diagnosed CP CML. Disclosures Gambacorti-Passerini: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Deininger: Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Celgene: Research Funding; BMS: Consultancy, Research Funding; Gilead: Research Funding; ARIAD: Consultancy; Ariad Pharmaceuticals, Bristol Myers Squibb, CTI BioPharma Corp, Gilead, Incyte, Novartis, Pfizer, Celgene, Blue Print, Galena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Mauro: Bristol-Myers Squibb: Consultancy. Chuah: Avillion: Honoraria; Chiltern: Honoraria; BMS: Honoraria, Other: Travel; Novartis: Honoraria. Kim: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Il-Yang: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Milojkovic: Novartis: Consultancy, Honoraria; Incyte: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. le Coutre: BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; ARIAD: Honoraria. García Gutiérrez: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Crescenzo: Pfizer: Employment, Equity Ownership. Leip: Pfizer: Employment, Equity Ownership. Bardy-Bouxin: Pfizer: Employment, Equity Ownership. Hochhaus: Novartis: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Ariad: Research Funding; MSD: Research Funding; BMS: Research Funding. Brümmendorf: Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Cortes: Sun Pharma: Research Funding; ARIAD: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Teva: Research Funding.

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Treatment Patterns Among Newly Diagnosed Multiple Myeloma Patients in the United States Veteran Population (2010-2015)

Blood ◽

10.1182/blood.v128.22.5952.5952 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5952-5952

Author(s):

Kejal Parikh ◽

Shivani Pandya ◽

Safiya Abouzaid ◽

Onur Baser ◽

Lin Xie ◽

...

Keyword(s):

Research Funding ◽

Cox Regression ◽

Treatment Patterns ◽

Novel Therapies ◽

Newly Diagnosed ◽

Employment Equity ◽

Chemotherapy Agent ◽

The Us ◽

Equity Ownership

Abstract Background: Despite a relatively higher incidence in the veteran population, there are few real-world claims-based analyses to describe Multiple Myeloma (MM) treatment patterns among this patient population (Landgren O, Blood, 2006). This study aimed to assess treatment patterns among newly diagnosed MM (ndMM) patients using the US Veteran Health Administration (VHA) data. Methods: This retrospective study identified adult patients with ≥2 claims for MM (ICD-9-CM code: 203.0x) 30 days apart and ≥1 treatment during identification period (1OCT2011-31MAR2015) from the VHA dataset. The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless patients died within 6 months (follow up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant (ASCT)), and no evidence of ASCT in the follow up period. A subsequent COT (COT2) was defined as the earliest occurrence of: the addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or a dose increase from maintenance to relapse therapy. Dexamethasone/prednisone[d] which were assumed to be included regardless of whether or not they were observed during the study period did not impact the ongoing COT. Treatment patterns during the follow-up period were initially examined among patients treated with novel (lenalidomide [R] and/or bortezomib [V] with or without chemotherapy agents) and non-novel therapies (≥1 chemotherapy agent, steroid monotherapy) and then compared among those initiating Rd and Vd. Time to next treatment (TTNT) was defined as the duration from initiation of COT1 plus any gaps before COT2. Kaplan Meier and Cox regression analyses were performed to evaluate TTNT and assess the impact of various predictors on TTNT among patients initiating Rd and Vd. Results: Of 1,183 patients that met the inclusion criteria, 55.4% (n=655) were treated with novel therapies and 44.6% (n=528) with non-novel therapies. Among patients treated with novel therapy, the majority initiated Rd (47.8%; n=313) as COT1 followed by Vd (31.2%; n=204), Vd with cyclophosphamide (11.5%; n=75), RVd (6.6%; n=43), Vd with a chemotherapy agent (2.4%; n=16) and Rd with a chemotherapy agent (0.6%; n=4).Rd initiators were significantly older (75.1 vs 70.6 years, p=0.0002) and a higher percentage was white (69.7% vs 47.0%; p<0.0001) than Vd treated patients. While the Charlson Comorbidities Index score did not differ between the two groups (3.6 vs 4.0, p=0.0583), a significantly higher percentage of patients treated with Vd had some comorbidities including hepatitis and renal disease. Among patients with laboratory tests, patients treated initially with Vd had lower hemoglobin (10.8 vs 11.4 g/dl, p=0.0012) and higher serum creatinine (2.3 vs 1.4 mg/dl, p<0.0001) during the pre-index period. The overall average treatment duration in COT1 was significantly longer among patients treated with Rd vs Vd (10.9 vs 7.0 months, p<0.0001). Among patients who were still on active COT1, the mean duration in COT1 was longer among patients treated with Rd than Vd (18.7 vs 13.3 months, p=0.0061). A significantly higher percentage of patients treated with Vd progressed to COT2 (52.5%, vs 26.2% p<0.0001) as compared to Rd. Among patients who progressed to COT2, those treated with Vd had a shorter TTNT compared to Rd (Mean: 9.3 vs 12.8 months, p=0.0049). After adjusting for baseline demographic and clinical factors using Cox regression, TTNT remained significantly shorter for Vd vs those treated with Rd (HR: 2.67, 95% CI: 1.9-3.7, p <0.0001). Conclusion: Slightly over half of MM patients in the US Veteran population were treated with a regimen containing novel therapies; Rd and Vd were the most commonly observed among these. Patients treated initially with Vd had a significantly shorter TTNT compared to those treated with Rd. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on Vd. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Baser:Celgene: Research Funding. Xie:Celgene: Research Funding. Patel:Celgene: Consultancy.

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Lenalidomide Plus Bortezomib and Dexamethasone in the Treatment of Newly Diagnosed Multiple Myeloma: Results from a Canadian Cost-Effectiveness Analysis

Blood ◽

10.1182/blood-2019-123636 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 70-70

Author(s):

Michael Sebag ◽

Julie Stakiw ◽

Thomas J. Stephens ◽

Amie Padhiar ◽

Tony Kim ◽

...

Keyword(s):

Cost Effectiveness ◽

Board Of Directors ◽

Research Funding ◽

Cost Effective ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Scenario Analyses ◽

Effectiveness Analysis ◽

Equity Ownership

Introduction: In the Southwest Oncology Group trial SWOG S0777 (NCT00644228), lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX; RVd) demonstrated superior median progression-free survival (PFS; 43 months vs. 30 months, P = 0.002) and overall survival (OS; 75 months vs. 64 months, P = 0.025) compared with Rd in patients with newly diagnosed multiple myeloma (NDMM) not eligible for immediate autologous stem cell transplantation (ASCT). This analysis compared the cost-effectiveness of RVd with existing treatment options for Canadian patients with NDMM not intended for ASCT (including LEN and DEX (Rd); and BORT, melphalan, and prednisone [VMP]), and regimens such as daratumumab plus VMP [D-VMP], which is currently under review by the pan-Canadian Oncology Drug Review (pCODR). Methods: The natural history of disease was modelled using a partitioned survival analysis and comprised of 3 health states (pre-progression, post-progression, and death). PFS and OS for RVd and Rd were estimated based on analysis of the SWOG S0777 trial data. Survival estimates for VMP and D-VMP were informed by a previously published network meta-analysis (NMA). Although cyclophosphamide, BORT, and DEX (CyBorD) is a commonly used therapy for MM patients in Canada, due to the lack of randomized trial data on its efficacy VMP was used as a proxy. Given the non-proportional hazards for PFS observed between regimens with a fixed duration (e.g. VMP) and those used until progression (e.g. Rd), a piecewise model was fit to the PFS data from the MM-020 trial comparing melphalan, prednisone, and thalidomide (MPT) and Rd, and hazard ratios (HR) from the NMA for VMP and D-VMP were applied to MPT. The OS curve for VMP was generated by applying the published HR to the modelled Rd arm. Given the paucity of OS data for D-VMP, this was assumed to be equivalent to RVd, based on feedback from clinical experts. A threshold analysis was also conducted to estimate the OS HR needed for D-VMP to be cost-effective at a threshold of Canadian dollars (CAD)100,000 compared with RVd. Quality-of-life estimates were obtained from data collected from transplant-ineligible patients in the MM-020 trial. Costs included drug acquisition and administration, supportive care and monitoring, adverse events, subsequent treatment, and end-of-life care. The analysis was conducted from the perspective of the Canadian public payer over a 30-year time horizon. Cost-effectiveness results were presented in terms of the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY). Costs and outcomes were discounted at a rate of 1.5% per year. The robustness of the results and the impact of the model's assumptions were tested in sensitivity and scenario analyses. Results: In the reference case, RVd was associated with the highest total number of life years gained and QALYs. ICERs for RVd were CAD 43,632 per QALY gained versus Rd, CAD 70,488 per QALY gained versus VMP, and RVd was superior to D-VMP (more QALYs and lower costs). Scenario analyses showed that the most sensitive factors were the use of the second-best fitting model for extrapolating OS (RVd vs. VMP ICER increased by CAD 13,007) and the assumption of no drug wastage (RVd vs. Rd ICER decreased by CAD 7,236). Age of patients at baseline was associated with substantial variation in ICER across all comparators, with older patients having larger ICERs. For D-VMP to be cost effective over RVd at the threshold of CAD 100,000, the required HR for OS will have to be 0.18 or better versus VMP in the ALCYONE (NCT02195479) trial; for comparison, the current PFS and time to second progression (PFS2) HRs have been reported as 0.43 and 0.59 in the ALCYONE trial. Conclusions: This cost-effectiveness analysis demonstrated that RVd is associated with both survival and QALY gains compared with treatments that are currently available or pending approval and is a cost-effective strategy in the management of patients with NDMM not intended for ASCT in Canada, a setting with a high unmet need in terms of patient survival. Disclosures Sebag: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Stakiw:Janssen: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Roche: Research Funding; BMS: Honoraria; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Lundbeck: Honoraria; Sanofi: Honoraria. Stephens:Amaris Consulting: Employment; Celgene Corporation: Consultancy. Padhiar:Amaris Consulting: Employment. Kim:Celgene Corporation: Employment, Equity Ownership. Shum:Celgene Corporation: Employment, Equity Ownership. Dhanasiri:Celgene Corporation: Employment, Equity Ownership. Trudel:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria; Astellas: Research Funding; Genentech: Research Funding; Sanofi: Honoraria; Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Real World Treatment Outcomes and Cost Among Newly-Diagnosed Multiple Myeloma Patients Treated with Bortezomib and Dexamethasone in Combination with Cyclophosphamide or Lenalidomide

Blood ◽

10.1182/blood.v128.22.5924.5924 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5924-5924

Author(s):

Lin Xie ◽

Kejal Parikh ◽

Safiya Abouzaid ◽

Shivani Pandya ◽

Onur Baser ◽

...

Keyword(s):

Healthcare Costs ◽

Research Funding ◽

Index Date ◽

Cox Regression ◽

Treatment Patterns ◽

Newly Diagnosed ◽

Employment Equity ◽

Equity Ownership ◽

Baseline Characteristics

Abstract Background: Despite an increasing incidence of multiple myeloma (MM) with advancing age and life expectancy, there are few real-world claims-based analyses describing treatment patterns and healthcare costs associated with use of novel treatments.1,2 This study aimed to assess treatment patterns and healthcare costs among newly-diagnosed MM patients using the US Medicare database. Methods: This retrospective study identified adult patients with ≥2 claims for MM (International Classification of Diseases, 9th Revision, Clinical Modification code: 203.0x) 30 days apart and ≥1 treatment during the identification period (01JAN2011-30JUN2014) from the 100% Medicare dataset. Medicare dataset contains medical and pharmacy claims submitted by healthcare providers, facilities and pharmacy. It includes comprehensive demographic information for beneficiaries and a longitudinal picture of their healthcare utilizations and costs .The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless the patient died in <6 months (follow-up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant [ASCT]), and no evidence of ASCT in the follow-up period. COT2 was defined as the earliest occurrence of: addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or dose increase from maintenance to relapse therapy. Steroids (dexamethasone/prednisone [d]) were assumed to be included regardless of whether or not they were observed during the study period; this did not impact the ongoing COT. Treatment patterns and healthcare costs during the follow-up period were compared among those initiating lenalidomide (R) with bortezomib (V) ± steroids (RVd) and cyclophosphamide (Cy) with bortezomib (bor) ± steroids (CyBorD). Time-to-next treatment (TTNT) was defined as the duration from initiation of COT1 plus any treatment gaps until the initiation of COT2. Kaplan Meier (KM), Cox regression analyses and a generalized linear model (GLM) were performed to evaluate TTNT, assess the impact of various predictors on TTNT, and estimate the 12-month per patient per month (PPPM) total healthcare costs respectively among patients initiating RVd and CyBorD. Results:After accounting for the patient selection criteria, 9.9% (n=345) of patients initiated RVd and 5.0% (n=175) initiated CyBorD as COT1. CyBorD-treated patients were significantly older (76.1 vs. 74.2 years, p=0.0009) with a higher age-adjusted Charlson Comorbidity Index score (9.5 vs 8.8, p=0.0119). The overall mean duration of COT1 was significantly longer among patients treated with RVd vs CyBorD (13.2 vs 8.5 months, p<0.0001). Among patients who completed COT1, the mean duration of COT1 was longer for patients treated with RVd vs. CyBorD (12.8 vs 6.7 months, p<0.0001). A higher percentage of patients treated with CyBorD progressed to COT2 (27.4%, vs 21.7% p=0.1491) versus RVd, however no significant difference was observed. Among patients who progressed to COT2, TTNT was significantly shorter among those treated with CyBorD vs RVd (Mean: 7.9 vs 15.9 months, p<0.0001). KM analysis suggested that patients initiating CyBorD progressed much faster than patients receiving RVd. After adjusting for baseline characteristics using Cox regression, TTNT remained significantly shorter for CyBorD vs. RVd treated patients (hazard ratio: 2.2, 95% confidence interval: 1.5-3.4, p=0.0002). Results from GLM analysis suggested that adjusted total PPPM cost during 12 months follow up was higher among patients treated with RVd vs. CyBorD ($13,941 vs $9,340, p=0.0001), and the majority of the extra cost are due to higher pharmacy costs for patients treated with RVd. Conclusion: Patients on RVd incurred higher costs, however, they progressed significantly slower and their TTNT was almost twice as long as for CyBorD patients. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on CyBorD. 1Song X, et al. Curr Med Res Opin 2015;32(1):95-103 2Teitelbaum A, et al. Oncologist 2013;18:37-45 Disclosures Xie: Celgene: Research Funding. Parikh:Celgene Corporation: Employment, Equity Ownership, Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Baser:Janssen Pharmaceuticals: Research Funding. Patel:Celgene: Consultancy.

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The Incidence of BCR-ABL Mutations and Their Impact on Outcome in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Nilotinib or Imatinib in ENESTnd: 36-Month Follow-up

Blood ◽

10.1182/blood.v118.21.2755.2755 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2755-2755

Author(s):

Timothy P. Hughes ◽

Dong-Wook Kim ◽

Gabriel Etienne ◽

Carmino De Souza ◽

Mineo Kurokawa ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Direct Sequencing ◽

Chronic Phase ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

T315i Mutation ◽

Equity Ownership

Abstract Abstract 2755 Background: In ENESTnd, nilotinib demonstrated superior efficacy vs imatinib in newly diagnosed patients (pts) with CML-CP, including a significantly reduced rate of progression to AP/BC on treatment. Here, we examined the occurrence of emergent mutations on treatment and their impact on response. Data on the incidence of mutations and impact on efficacy with a minimum follow-up of 36-months (mo) for all pts will be presented. Methods: Pts with CML-CP were randomized to receive nilotinib 300 mg BID (n = 282), nilotinib 400 mg BID (n = 281), or imatinib 400 mg QD (n = 283). Mutation testing was performed by direct sequencing of the kinase domain (amino acids 230 to 490; sensitivity, 10%-20%) in a central lab at: baseline, 5-fold increase in BCR-ABL levels, lack of MMR at 12 mo, loss of MMR, or treatment discontinuation. Results: With a minimum follow-up of 24 mo, twice as many pts had emergent mutations on imatinib (n = 20) vs nilotinib (n = 10, nilotinib 300 mg BID; n = 8, nilotinib 400 mg BID), with the majority of mutations emerging in pts with high and intermediate Sokal scores (Table). Of pts with mutations emerging on imatinib, the majority (65%) had nilotinib-sensitive, imatinib-resistant mutations; whereas nilotinib was effective in preventing the emergence of clones with nilotinib-sensitive mutations. The incidence of T315I mutations was similar for the nilotinib (n = 3, nilotinib 300 mg BID; n = 2, nilotinib 400 mg BID) and imatinib (n = 3) arms and most of these T315I mutations (6/8) were detected within the first 12 mo of therapy. All but 1 pt with the T315I mutation had a high Sokal risk; the other pt had an intermediate Sokal risk. Overall, across the 3 treatment arms, the incidence of any mutation was 14% in pts who had BCR-ABLIS > 10% at 6 mo vs 4% in pts with BCR-ABLIS ≤ 10% at 6 mo. The majority of pts with emerging mutations had suboptimal response (SoR) or treatment failure (TF) on treatment; all pts with the T315I mutation had SoR or TF. Of the pts with mutations, 1/10 pts on nilotinib 300 mg BID, 2/8 pts on nilotinib 400 mg BID, and 7/20 pts on imatinib, progressed to AP/BC on treatment. BCR-ABL mutations did not account for all cases of progression to AP/BC, loss of CCyR, and loss of MMR on treatment (Table). Of the pts who achieved an MMR on treatment, 0/203 (0%), 2/192 (1%) and 3/131 (2%) had a mutation and lost MMR with nilotinib 300 mg BID, nilotinib 400 mg BID or imatinib, respectively. Conclusions: Nilotinib may be more effective in preventing the development of emerging mutations vs imatinib. More pts with new mutations progressed to AP/BC on imatinib than on nilotinib. These data suggest that deeper molecular responses with nilotinib protect from the development of emerging mutations and progression to AP/BC vs imatinib. Disclosures: Hughes: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kurokawa:Novartis Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kalaycio:Novartis Pharmaceutical: Honoraria, Research Funding, Speakers Bureau. Saglio:Bristol Myers Squipp: Consultancy, Speakers Bureau; Novartis Pharmaceutical: Consultancy, Speakers Bureau; Pfizer: Consultancy. Larson:Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding. Kantarjian:Pfizer: Research Funding; Novartis: Research Funding; Novartis: Consultancy; BMS: Research Funding. Hoenekopp:Novartis Pharmaceutical: Employment, Equity Ownership. Shou:Novartis: Employment. Yu:Novartis: Employment, Equity Ownership. Blakesley:Novartis Pharmaceutical: Employment. Rosti:Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Roche: Honoraria. Hochhaus:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis Pharmaceutical: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding.

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