Double Refractory Myeloma: Analysis Of Clinical Outcomes and Medical-Resource Utilisation In a Single Centre
Authors: Gooding Sarah , Lau I-Jun , Sheikh Mimi , Roberts Pamela , Wong Julia , Dickens Emmy , Elvidge Jamie , Lee Dawn , Ramasamy Karthik 
Published: October 2019

Abstract

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.