ALBERT

Description: 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.

Description: Introduction: In clinical studies of patients (pts) with International Prognostic Scoring System (IPSS)-defined Low- to Intermediate-1-risk myelodysplastic syndromes (MDS), dose modification of lenalidomide (LEN) has been commonly used by physicians to sustain control of disease while managing toxicities. A previous real-world setting analysis has shown that dose modification of LEN in pts with multiple myeloma was associated with longer duration of therapy (DOT) and improved outcomes versus pts without dose modification (Usmani SZ, et al. Blood. 2014;124:abstract 2655). This study aimed to evaluate whether LEN dose modification in pts with MDS is associated with longer DOT and improved outcomes in a real-world setting using various measures available from claims data. Methods: A retrospective study was conducted using a large US medical and pharmacy claims database, covering 〉 25 million commercial- and Medicare-insured lives annually. MDS pts with ≥ 2 outpatient claims or ≥ 1 inpatient medical claim associated with a diagnosis of MDS (ICD-9-CM codes 238.72-238.75) were identified; the first such claim was defined as the index date. A minimum of 12 months' pre-index enrollment and 6 months' post-index continuous enrollment between Jan 1, 2008 and Dec 31, 2013 was required. The inclusion criteria included pts with MDS treated with LEN who did not have claims for stem cell transplantation or high-risk disease at diagnosis. Clinically relevant metrics, including DOT, time to acute myeloid leukemia (AML), time to next therapy, time to advancement to high-risk disease (as measured by ICD-9-CM code 238.73), and time to red blood cell transfusion dependence, were compared in pts with and without LEN dose modifications (defined as: change in dose [mg/day], dose interruption of 10-60 days, or both); time-to-progression (TTP) was defined as a composite of the above. Charlson Comorbidity Index (CCI) and MDS Comorbidity Index (MDS-CI) (Della Porta MG, et al. Haematologica. 2011;96:441-9) scores were determined to compare baseline measures between groups. Adjusted hazard ratios (HRs) were calculated using a Cox proportional hazards model adjusted for age group, sex, and MDS-CI risk group at LEN initiation. Results: Of 529 pts who met inclusion criteria, 245 (46%) had LEN dose modifications, including 135 pts with ≥ 1 dose change and 201 pts with ≥ 1 dose interruption; 91 pts had both. Overall, 54% of pts were aged ≥ 75 years; age (P = 0.647), CCI (P = 0.867), and MDS-CI (P = 0.967) did not differ between pts managed with and without LEN dose modifications. For pts without dose modifications, the rate of cytopenias within 14 days prior to discontinuation (50.7%) did not significantly differ from the rate of cytopenias within 14 days prior to first modification for pts with dose modifications (50.2%; P = 0.920). Median time to first dose modification was 1.9 months (range 0.4-23.2). Median DOT was 12.6 months for pts with LEN dose modification versus 1.9 months for pts without dose modification (P 〈 0.0001). The DOT benefit did not differ whether the modification was a dose change or an interruption (P = 0.115). Most pts initiated LEN at a 10 mg/day dose; the most common change for those who modified was to reduce to a 5 mg/day dose. Median TTP was 20.6 months for pts with dose modification versus 13.7 months for those without; the adjusted HR was 0.703 (95% confidence interval 0.541-0.914) (P = 0.009). Pts with dose modification had statistically significant improvements in time to AML (P = 0.018), time to next therapy (P = 0.002), and time to high-risk disease (P = 0.043) compared with pts without dose modification. Conclusions: For pts medically managed with lenalidomide treatment for myelodysplastic syndromes in the USA, dose modifications during their treatment were associated with longer therapy duration, improvement in time to progression to AML or high-risk disease, and improved time to next therapy compared with pts without lenalidomide dose modification. Modifications were utilized in 46% of pts and the median time to modifications was similar to the DOT in those not receiving modifications, suggesting dose modifications may be worth considering for some pts who discontinue lenalidomide. This analysis supports lenalidomide dose modification in the treatment of MDS as an effective technique in the real-world setting for pts to achieve better treatment outcomes based on proxy measures available from claims data. Disclosures Binder: Celgene Corporation: Employment, Equity Ownership. Fliss:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Rizvi:Celgene Corporation: Employment, Equity Ownership. Corvino:Genesis Research LLC: Consultancy. Arikian:Genesis Research LLC: Consultancy. Surinach:Genesis Research LLC: Consultancy. Lee:Genesis Research LLC: Consultancy.

Description: Introduction. A previous study of patients (pts) with newly-diagnosed multiple myeloma (NDMM) showed that initial high monthly total costs declined over time until returning near initial levels upon pts advancing to later lines of treatment (Tx) at disease progression (Arikian, CMRO 2015). However, the longer-term economic implications of the choice of first-line Tx, regardless of subsequent Tx regimens, have not been described. We utilized an intent-to-treat approach to further evaluate and compare the total costs of NDMM patient cohorts initiated on Lenalidomide (LEN) or Bortezomib (BORT)-based Tx and followed these patients over 54 months. Methods: A retrospective analysis was performed using a large US medical and pharmacy claims database, covering 〉 25 million commercial and Medicare lives annually. NDMM patients were defined as having ≥ 2 outpatient claims or ≥ 1 inpatient medical claim 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 ≥ 12 months' pre-index and ≥ 6 months' post-index continuous enrollment from 2006 - 2013, and evidence of initiation of a subsequent line of therapy. Pts with claims for stem cell transplantation (SCT) or receiving concurrent LEN plus BORT as first-line Tx were excluded. The analysis focused on cohorts of NDMM pts receiving LEN or BORT-based first line Tx, who progressed to one or more subsequent lines of Tx, using time to next therapy (TTNT) as a proxy for progression. Pts receiving LEN or BORT-based first line Tx were randomly matched 1:1 on age (+/- 3 years at index), sex, baseline Charlson comorbidity score (+/- 1), and presence of renal disease. Using methods similar to those described by Gaultney(J Clin Pharm Ther, 2013), pts' average monthly costs and standard errors were determined, including medical and pharmacy costs, and total cost patterns were calculated from first line Tx initiation until the end of patient eligibility or 54 months. Results: 1,181 NDMM pts receiving LEN (N=444) or BORT-based (N=737) first line Tx with complete data available through initiation of subsequent line of Tx were identified. After matching, 856 NDMM patients remained (428 LEN, 428 BORT). Monthly total direct medical plus pharmacy costs for these pts were in excess of $12,000 at initiation. Total monthly costs declined quarterly for each cohort until the median TTNT was reached (20 months for BORT; 37 months for LEN). As increasing numbers of pts in each cohort then advanced to subsequent lines of therapy, costs of those patients began to offset continued cost declines for pts still on first line of therapy. Over the full 54 month follow-up period, total monthly costs averaged $8,324 (SE = $370.30) for pts initiated on LEN vs. $10,728 (SE = $500.55) for pts initiated on BORT (p-value

Description: Introduction: Multiple clinical studies in patients (pts) with newly diagnosed multiple myeloma (NDMM) have shown benefits from continuous lenalidomide (LEN) treatment (Tx), including extended progression-free survival (PFS), time to progression (TTP), and overall survival (OS) (Facon, Blood 2013; Palumbo, NEJM 2012). Dose modifications are commonly utilized by physicians as part of continuous Tx plans to sustain control of disease while managing toxicities. Previous analysis has shown that dose modification of LEN was associated with longer duration of therapy (DOT) relative to non-dose modification, in the real-world setting (Lang, Blood 2013). This study aimed to evaluate whether LEN dose modification is associated with a longer TTP in NDMM pts, utilizing time to next therapy (TTNT) as a proxy measure available from claims data. Methods: A retrospective study was conducted using a large US medical and pharmacy claims database, covering 〉 25 million lives annually. NDMM pts 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. A minimum of 12 months' pre-index enrollment and 6 months' post-index continuous enrollment between Jan 1 2006 and December 31 2012 was required. The analysis focused on NDMM pts treated with LEN who did not have claims for stem cell transplantation (SCT), to avoid DOT limitations imposed by fixed-length induction Tx. Median DOT and TTNT were compared in NDMM pts with and without LEN dose modifications (dose increase or decrease). Charlson comorbidity scores were determined to compare baseline measures between the groups. Results: Of the 1,360 pts who met the inclusion criteria, 470 (35%) had LEN dose modifications, including 154 pts with at least one dose increase and 421 pts with at least one dose decrease. The majority of pts had an initial dose of 25mg. The median DOT was 447 days in pts with LEN dose modification and 182 days in those pts with no dose modification (p 〈 0.001). The median DOT in pts with dose modification was consistent regardless of whether they experienced a dose increase or decrease, with no significant difference. The median TTNT in pts with LEN dose modification was 3.5 yrs compared to 2.0 yrs in pts without dose modification (p 〈 0.001; Figure 1). Charlson comorbidity scores were similar in pts with and without LEN dose modification. Figure 1 Figure 1. Conclusions: For non-SCT NDMM patients treated with LEN, dose modifications during their treatment were associated with a doubling of the median therapy duration and a 71% longer median TNTT, compared to pts without LEN dose modification. The DOT and TTNT in pts with dose modification were similar to median values reported for the LEN continuous Tx arm of the FIRST clinical trial (Facon, Blood 2013). This analysis suggests that LEN dose modification in the Tx of NDMM may be an effective tool in the real-world setting for pts to achieve sustained disease Tx and the associated prolonged time to progression, based on the proxy measure of TTNT. Disclosures 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. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma patients. Binder:Celgene Corporation: Employment, Equity Ownership. Milentijevic:Celgene Corporation: Consultancy. Hu:Celgene: Employment. Nagarwala:Celgene Corporation: Employment. Corvino:Genesis Research LLC: Consultancy. Arikian:Genesis Research: Consultancy. Surinach:Genesis Research LLC: Consultancy. Harwin:Celgene Corporation: Honoraria.

Description: Background: BT is an important public-health challenge in Italy. Seminal work has begun to better characterize disease prevalence, treatment patterns, and institutional capabilities within Italy. Objective: Evaluation of current BT prevalence and treatment in Italy was done using proprietary IMS Health hospital audit data as the basis of a targeted survey of hematologists, pediatricians, and internists treating BT. We estimated the prevalence and distribution of patients with transfusion-dependent (TD) BT major (BT-M) and intermedia (BT-I), and non-transfusion-dependent BT (NTD BT), and characterized current treatment patterns. Methods: A preliminary list of possible BT-treating centers was extracted from the IMS Health audit of hospitals and treatment centers across Italy, covering 656 public hospitals and accounting for 205,021 beds (85% of hospital capacity in Italy).The IMS Health hospital audit also included 95% of the pharmaceutical Direct Patient Distribution channel. This list was reviewed to identify centers receiving iron-chelating agents, thus identifying a total of 365 potentially BT-treating hospitals. One hematologist or pediatrician in each potential hospital ward was contacted by telephone. The physician was asked to provide details about the number of TD BT-M, TD BT-I, and NTD BT patients managed in their ward. In case of refusal to provide the required information, telephone or in-person interviews were organized with other specialists in the same facility. We identified 124 treatment centers, 114 of which were successfully surveyed (92% completed the survey). Subsequently we used a web-based questionnaire to ask a geographically stratified sample of 60 treating physicians about general treatment patterns, with a focus on potential drivers of health-care resource utilization. Responding physicians each referenced 3-4 records for patients currently under their care to inform their responses to our survey, and 205 records were referenced in total: 162 TD and 43 NTD patients. Results: In the 114 treatment centers surveyed, a total of 5,748 TD BT patients under regular treatment were reported, plus 1,296 additional patients receiving occasional treatment (NTD BT). Distribution of TD patients was heterogeneous, with the highest prevalence in Sicily, Sardinia, and Puglia. These regions each had 〉 500 TD patients and hosted in total 3,051 TD patients (Table). National patient volume was highly concentrated with the 7 largest centers managing 1,766 TD patients. Based on the information in 205 patient records, complete blood count, ferritin level, echocardiography, and T2*-weighted MRI were the tests most commonly performed in the preceding 12 months. Of 162 TD patient records reviewed, 83 patients required 1-2 units of red blood cells per month, while 78 patients required ≥ 3 units per month (this information was not captured in 1 patient record). Deferasirox was the most commonly administered chelation treatment in TD patients, prescribed to 109 of 162 patients. Most TD patients (n = 126) had previously had a change of iron chelation treatment; 72 of these switched from deferoxamine to another agent. In-patient hospitalizations were estimated at 9 days/year, 7 days/year, and 4 days/year for TD BT-M, TD BT-I, and NTD BT patients, respectively. Endocrine pathologies were the most commonly reported comorbidity in all groups; 36 patients required medical treatment. Hepatitis C virus infection and hepatic and cardiac complications were also reported. Conclusions: Prevalence of BT is regionally focused and likely to consume significant health-care resources for management of the disease and associated comorbidities. Although the telephone and web surveys used for our project were not designed to be a clinical trial, we were able to assess practices by a number of physicians (n = 60) for patients (n = 205) that were representative of the distribution of BT across Italy. We also screened the overall BT caseload of up to 365 potentially BT-treating centers in the country. Our survey complements recent work to understand the burden of this disease in Italy. Disclosures Angelucci: Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Burrows:Celgene Corporation: Research Funding; IMS Health s.r.l.: Employment. Losi:IMS Health: Employment; Celgene Corporation: Research Funding. Bartiromo:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment, Equity Ownership.

Description: Introduction: Multiple myeloma (MM) is an incurable hematologic malignancy. Due to the introduction of newer MM treatments, patient survival has increased and outcomes have improved over the last 10 years, but not without questions arising regarding the overall cost of care of these patients. Recent studies suggest that medical (nondrug) costs account for the majority of the total expenses of relapsed MM treatment (Gaultney 2013). This study seeks to describe the nature of resource utilization in patients with newly-diagnosed MM based upon real-world data from a US claims database. Methods:We investigated the total health care cost for patients over the first 2 years after initial diagnosis by analyzing a commercial claims database containing anonymized health data from ~20 million individuals, including prescription drugs and clinical use and costs across inpatient and outpatient services. The study population included all patients diagnosed with MM (ICD-9-CM: 203.0X) between January 2008 and June 2013, who were free of MM claims 12 months prior to the first diagnosis and were continuously enrolled in the health plan for at least an additional 24 months following the initial diagnosis. We estimated total health care costs by including both payments made by insurers and patient out-of-pocket medical expenses. Results: A total of 6,238 patients were included in the analysis, of whom 702 (11.3%) received stem cell transplant (SCT). The mean age was 63.1 years and 49.6% were males. Total health care expenses amounted to $65,607 per patient per year (over the first 2 years after diagnosis), which included inpatient and outpatient services as well as pharmacy costs. When the costs were analyzed by transplantation status, annual costs per patient were $182,061 for those receiving SCT compared with $50,840 for those who did not receive SCT. For patients who received SCT, outpatient services accounted for the highest percentage of total cost at 45.8%, followed by inpatient care (33.9%) and drug cost (20.3%). For patients who did not receive SCT, outpatient care remained the most expensive cost component at 54.0%, followed by inpatient care and drug cost (23.0%, respectively). Compared with the first year of treatment, total health care expenses over the second year were lower by 44.0% in patients who received SCT ($233,467 to $130,654) and by 27.1% in patients who did not receive SCT ($58,819 to $42,861). Conclusion: The results from this analysis suggest that medical costs accounted for about three-fourths of the total health care costs over the first 2 years in newly diagnosed MM patients, with drug costs accounting for the remaining fourth. MM treatment expenses were considerably higher in the first year following diagnosis than in the subsequent year. Disclosures Hu: Celgene: Employment. Cai:Celgene Corp: Employment, Equity Ownership. Binder:Celgene Corp: Employment, Equity Ownership. Monzini:Celgene Corp: Employment, Equity Ownership. Nagarwala:Celgene Corp: Employment.

Description: Background: Significant increase in life expectancy has been observed in patients with β-thalassemia in recent years. The improved survival, however, is accompanied by significant ongoing healthcare needs related to the chronic condition; therefore, quality of life (QoL) has emerged as a fundamental focus of comprehensive patient care. We compared QoL outcomes between transfusion-dependent (TD) and non-transfusion-dependent (NTD) patients with β-thalassemia in the routine clinical care setting. Method: Adult patients with β-thalassemia were prospectively enrolled in an observational study in Italy, Greece, Lebanon, and Thailand. All patients completed Short Form 36 Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy (FACT)-Anemia (An) questionnaires at baseline, and then once every 3 weeks using a hand-held electronic device. This analysis evaluated QoL between TD and NTD patients at study entry. Transfusion dependent was defined as receiving ≥ 6 red blood cell (RBC) units in the 24 weeks prior to study entry and no transfusion-free period for ≥ 35 days during that period. Results: A total of 102 patients with β-thalassemia were enrolled, of which 52 were TD and 50 NTD. The mean age of patients was 31.2 years and 70 (68.6%) were females. On average, patients with TD β-thalassemia were 3.6 years younger (P= 0.06) and had moderately higher hemoglobin values at baseline (8.8 vs 8.2 g/dL; P= 0.02). At study entry, all (100%) patients with TD β-thalassemia had received RBC transfusions within the 24 weeks prior to study entry, as per inclusion criteria, versus 5 (10%) patients with NTD β-thalassemia who had received RBC transfusions during the same time period. Patients with NTD β-thalassemia reported lower QoL on all domains and summary scores as captured by the SF-36v2 questionnaire, except for Role-Physical. On average, patients with NTD β-thalassemia experienced statistically significant lower QoL versus their TD counterparts on the domains of General Health (39.5 vs 44.0; P= 0.01), Vitality (49.3 vs 53.7; P= 0.01), and Mental Health (46.8 vs 50.8; P= 0.01), and in the Mental Component Summary Score (46.5 vs 50.8; P= 0.01). Similarly, patients with NTD β-thalassemia reported worse QoL scores from the FACT-An questionnaire on all domains and statistically significant differences were observed for Emotional Well-Being (18.5 vs 20.0; P= 0.02), Functional Well-Being (20.0 vs 23.2; P 〈 0.01), and FACT-General (82.9 vs 89.4; P= 0.01). Conclusions: In the routine clinical care setting, there are critical unmet medical needs for patients with NTD β-thalassemia as they experience worse QoL on many domains compared with patients with TD β-thalassemia. There is a need for new interventions to treat patients with NTD β-thalassemia and reduce their burden of disease. Disclosures Cappellini: Vifor: Honoraria; Novartis: Speakers Bureau; Celgene: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau. Kattamis: National and Kapodistrian University of Athens: Employment; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Viprakasit: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Siriraj Hospital: Employment; Shire: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Sutcharitchan: Celgene: Research Funding; Chulalongkorn University: Consultancy, Employment. Mahmoud: Celgene: Employment. Pariseau: Celgene: Employment. Laadem: Celgene: Employment, Equity Ownership. Khan: Nathan S. Kline Institute for Psychiatric Research; Manhattan Psychiatric Center: Employment. Hu: Celgene: Employment, Equity Ownership. Taher: Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding.