ALBERT

Description: Langmuir DOI: 10.1021/la203848r

Description: Background Introduction of proteasome inhibitors and immunomodulatory agents over the last decade has improved survival for multiple myeloma (MM) patients. A retrospective analysis of patients who developed resistance/intolerance to these agents showed a median overall survival (OS) and progression-free survival (PFS) of 9 months and 5 months, respectively (Kumar et al. 2012). Recent clinical trials have focused on improving outcomes for these double-refractory (DR) patients. However very limited published data from real world clinical practice is available on clinical outcomes and medical-resource utilisation (MRU) costs for this cohort of patients. We have analysed clinical outcomes and patient-level MRU costs of double-refractory/intolerant patients in a single centre. Methods Data on clinical outcomes, anti-myeloma therapies prescribed and MRU were obtained from a single centre in Oxford, UK, for 36 MM patients who have received four lines of treatment between 2011 and 2013. Six patients had not received prior bortezomib due to neuropathy. For ease of comparison and uniformity, thirty patients pre-treated with lenalidomide and bortezomib who had progressed on last therapy were included in this analysis (83% of the cohort). Clinic attendances, inpatient admissions, supportive therapies, transfusions and blood tests from start of fourth-line therapy until death or last follow-up were retrieved from health care records. Survival analysis was performed; Kaplan–Meier survival plots were generated to evaluate OS and PFS following initiation of fourth-line therapy. The occurrences of MRU were extracted to estimate the use and cost of each, using the UK NHS schedule of reference costs 2011-12 and published sources. Results Patients were selected for analysis on the basis of having received/receiving four lines of anti-MM therapy. Patient characteristics are summarised in Figure 1. Median age at diagnosis was 65.3 years (48–83 years). When offered a choice of therapy 77% of patients preferred an active treatment to care with palliative intent. The mean age of those who chose palliative care was 75.8 years compared to 63.7 for active therapy (p = 0.003). Treatment regimens were typically bendamustine based (53%), retreatment with bortezomib (10%) or lenalidomide based (27%). Patients were treated for a mean of 15.3 weeks (SD: 11.3). There were 42 hospital admissions reported during fourth-line, lasting 8 days on average. Patients required 6.8 red blood cell units and 2.9 platelet units on average. At least one RBC and platelet transfusion was required by 22 and 13 patients respectively. Median PFS in this cohort was 11 weeks and median OS was 23 weeks; however, the sample size was too small to obtain definitive PFS or OS conclusions. There was steep drop in survival early on (Figure 2), with a small number of patients surviving over a longer period. The most common Grade 3-4 adverse events were anaemia (60%), thrombocytopaenia (57%) and bone pain (37%). Eighteen out of the 30 patients had died by the end of follow-up, of whom 78% died in hospital. Prolonged inpatient stays, frequent adverse events and high transfusion requirements suggest poor quality of life (QoL) among these patients. Outpatient and day therapy unit attendances occurred frequently, with 4.3 and 12.6 per patient respectively over the mean treatment duration of 15.3 weeks. Investigations including CT and MRI scans were performed in 33% of patients. Blood tests were frequent, with mean full blood count testing of 21.6 per patient. The mean drug cost of fourth-line anti-MM therapy was £5,101 per patient. The mean MRU cost during fourth-line therapy was £11,160: clinical attendances £5,015 (45%); inpatient admissions £2,999 (27%); transfusions £2,479 (22%); supportive therapy £498 (4%); blood tests £169 (2%). The mean total cost of treatment plus MRU was therefore £16,260 [£9,201–23,320]; £1,066 per week on treatment. Conclusion Over 75% of myeloma patients in the fourth-line setting want to be treated with an active intent to improve survival. PFS and OS in our cohort were similar to published estimates. These patients, due to the nature of their disease, have high MRU costs. Therapies that induce higher response rates or reduce disease progression could lower MRU costs and improve QoL. Our data will provide an optimal comparison when formal cost-effectiveness evaluation is performed with new therapies for this DR cohort. Disclosures: Gooding: Celgene: Unrestricted Educational Grant Other. Lau:Celgene: Unrestricted Educational Grant Other. Sheikh:Celgene: Unrestricted Educational Grant Other. Roberts:Celgene: Unrestricted Educational Grant Other. Wong:Celgene: Unrestricted Educational Grant Other. Dickens:Celgene: Unrestricted Educational Grant Other. Elvidge:Celgene: Consultancy. Lee:Celgene: Consultancy. Ramasamy:Celgene: Honoraria, Unrestricted Educational Grant Other.

Description: Background: Multiple myeloma remains an incurable disease, placing a significant burden on patients (pts), families, and healthcare systems. Bortezomib (BORT) and IMiDs® immunomodulatory agents (thalidomide and lenalidomide [LEN]) have improved progression-free survival (PFS), time to progression, and overall survival (OS). However, over time, nearly all pts become refractory which greatly impacts prognosis (median OS, 3-9 mos). In the absence of approved treatments, guidelines recommend clinical trials or retreatment with agents that were previously effective, but published data in the appropriate pt population for current care (CC) options are limited to those from small, observational, early-phase studies. There is a need for newer effective treatments; however, access is increasingly being determined by the demonstration of both clinical and economic value. POM + LoDEX demonstrated a significant OS benefit vs. high-dose dexamethasone (HiDEX) in the pivotal phase 3 MM-003 study (San Miguel, Lancet Oncol, 2013). POM + LoDEX has EU approval in RRMM pts in whom BORT and LEN failed. Objective: Explore the cost-effectiveness of POM + LoDEX vs. CC from a UK and Ireland healthcare payer perspective. Methods: A de novo pharmacoeconomic evaluation was conducted to compare costs and outcomes of POM + LoDEX to CC in the UK and Ireland. CC included BORT retreatment (intravenous [IV] or subcutaneous), LEN (oral), and bendamustine (IV) regimens. Efficacy data were sourced from MM-003 and 2 observational studies: a dataset for CC (Gooding, 2013; n = 30 pts primarily treated with BORT, bendamustine, or LEN; 100% received prior BORT and LEN) and a dataset for BORT + LEN (Jimenez-Zepeda, 2013; n = 30, 80% received prior BORT, 73% prior LEN). Validation of the approach and all model assumptions was achieved through extensive clinical and health economic expert consultation and by comparing comparator arm outcomes from observational data to the MM-003 (HiDEX) control arm data. The health economic model used a partitioned survival structure with OS and PFS parametric curves fitted to the datasets to estimate the number of pts at each time point expected to be preprogression, postprogression, or dead. Time to treatment failure curves were estimated to allow treatment discontinuation modelling. EQ-5D data, collected as part of MM-003, were used to inform quality of life (QOL) weights. A utility regression equation was developed to account for important covariates and allow utility to vary over time. The economic evaluation included the cost of treatment, administration, monitoring, tests, adverse events (AEs), blood transfusions, concomitant medication, and terminal care. Costs are presented in US dollars using an exchange rate of 0.74 per € and 0.58 per £. Costs and outcomes were modeled to estimate cost per life year (LY) and cost per quality-adjusted life year (QALY) gained over a lifetime horizon. Results: In the base-case analysis, POM + LoDEX was associated with a total incremental cost of $59,250 per pt over a lifetime horizon compared with CC (Table 1). Pts who receive POM + LoDEX are predicted to live for a mean of 2.2 years, compared with 1.2 years with CC. This represents an additional 0.6 QALYs. The model predicts a deterministic incremental cost-effectiveness ratio (ICER) of $100,920/QALY compared with CC, while the probabilistic ICER obtained through 1000 probabilistic model runs was consistent at $101,947/QALY. Table 1 : Base-Case Cost-Effectiveness Results Model Results POM + LoDEX CC Difference Clinical outcomes Median OS, mos 12.7 5.5 7.2 Mean predicted life-years (over a pt lifetime) 2.2 1.2 1.0 QALYs 1.3 0.7 0.6 Cost outcomes, US dollars Medication and administration $84,698 $29,880 $54,818 Monitoring $8230 $4489 $3741 AE management (outpatient visits and hospitalization) $7135 $6444 $691 Total $100,063 $40,813 $59,250 ICER—Cost/LY $58,112 ICER—Cost/QALY $100,920 Conclusion: There are limited alternative treatment options available in the UK and Ireland for RRMM pts. None have a proven effect on survival leaving pts to face potentially ineffective retreatments. End-of-life drugs that significantly improve survival and QOL and address unmet need can be considered to be cost-effective at a higher “willingness to pay” threshold. POM, an oral therapy with significant PFS, survival, and QOL with a known safety profile, is likely to be a cost-effective use of healthcare resources. Disclosures Dhanasiri: Celgene Corp: Employment, Equity Ownership. Lee:Celgene Corp: Consultancy. Sternas:Celgene Corp: Employment, Equity Ownership. Yu:Celgene Corp: Employment, Equity Ownership. Zaki:Celgene Corp: Employment, Equity Ownership. Elvidge:Celgene Corp: Consultancy.