ALBERT

Description: Background Multiple myeloma (MM) is the second most common hematologic cancer in adults. Novel agents, including thalidomide, bortezomib, and lenalidomide, have led to improved overall survival (OS) in MM, but the disease remains generally incurable with the majority of patients inevitably relapsing after front-line therapy (FLT). In a multi-center observational analysis of 383 MM patients (treated between 2007 and 2010), median progression-free survival (PFS) and OS from treatment after first relapse were 13 and 35 mos (Durie ASCO 2012; abs 8095). According to NCCN guidelines, retreatment with primary therapy may be considered if relapse occurs more than 6 mos after discontinuation of primary therapy, otherwise a switch in regimen is recommended (NCCN MM Guidelines v.4 2015). Treatment patterns and outcomes in RRMM remain to be elucidated. We examined treatment use, retreatment and therapy switch patterns, and outcomes among patients with RRMM initiating second-line therapy (SLT). Methods We conducted a retrospective cohort study using a large, national, US claims database. Adult patients with MM who initiated cancer-specific systemic therapy between Jan 2008 and Feb 2014, without evidence of transplantation, were identified. Newly diagnosed MM patients were followed from the first claim for MM. Continuous enrollment in the health plan for 12 mos pre-diagnosis (with no claim for MM) through at least the start of SLT was required. FLT began with the first claim for MM-directed systemic cancer therapy. Unique agents administered within 90 days of FLT initiation constituted a regimen. Continuation of FLT regimen (or part thereof) or monotherapy within 3 mos of the end of the initial regimen was considered part of FLT. SLT after first relapse for RRMM was identified accordingly: 1) a treatment gap 〉6 mos between end of FLT and start of a second regimen (retreatment or switch), 2) start of a follow up regimen (retreatment) with a treatment gap of 〉3 and up to 6 mos after end of FLT, or 3) a switch to another drug combination after FLT regimen. Analyses were conducted from the first claim for SLT. SLT ended at the earliest of start of a new drug, death, or end of study period (Feb 2014). MM drug combinations were based on all unique MM systemic therapy agents received within start and end date for SLT. Vital status information was ascertained from the Social Security Death Index. Results We identified 249 patients with RRMM receiving SLT. Approximately half (49%) were male; 29% and 43% were aged 65-74 and 75 years or older, respectively. SLT regimens were: lenalidomide±dexamethasone (R±d, n=70 [28%]), bortezomib±d (V±d 61 [25%]), other (58 [23%], see Table 1), V+other (25 [10%]), R+other (14 [6%]), V-cyclophosphamide±d (VC±d, 13 [5%]), and VR±d (8 [3%]). The switch and retreatment patterns from FLT to SLT are depicted in Table 1. Among patients with treatment-free interval (TFI, time from end of FLT to start of SLT) 〉6 mos (n=64) vs ≤6 mos (n=185), 18 (28%) vs 17 (9%) were retreated with the same primary regimen in SLT, respectively. Median duration of SLT was 6.3 (95% CI: 5.6, 6.9) mos (Fig. 1) and of FLT was 6.8 (95% CI: 6.0, 7.8) mos. The 1-year OS probability from initiation of SLT for RRMM was 82% (95% CI: 76%, 86%). Conclusions Among patients with RRMM treated in the USA, V- and R-based regimens were the most common at first relapse. The vast majority of patients (91%) with TFI ≤6 mos switched therapy at time of relapse in concordance with NCCN guidelines. The relatively short duration of SLT (median 6.3 mos) in this study compared with PFS from treatment after first relapse (median 13 mos, Durie ASCO 2012; abs 8095) in a cohort of patients with RRMM, suggests that the majority of patients discontinue SLT prior to disease progression. These findings highlight the need for newer SLT regimens that are effective and more sustainable compared with current treatment choices. Table 1. Switch and Retreatment Patterns from FLT to SLT among Patients with RRMM. SLT V-based R-based VR-based Other FLT V-based 41 (41%) 49 (58%) 4 (50%) 15 (26%) R-based 33 (33%) 13 (15%) 2 (25%) 12 (21%) VR-based 9 (9%) 6 (7%) 2 (25%) 19 (33%) Other* 16 (16%) 16 (19%) 0 (0%) 12 (21%) Total 99 (100%) 84 (100%) 8 (100%) 58 (100%) *Other combinations consisted of a subset of the following agents: cyclophosphamide, melphalan, vincristine, doxorubicin, interferon-alpha, pomalidomide, thalidomide, carfilzomib, dexamethasone, prednisone Disclosures Romanus: Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Jhaveri:Sanofi: Equity Ownership; Takeda Pharmaceutical Company Limited: Equity Ownership; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Labotka:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Henk:Optum (a consulting firm retained by Takeda to conduct the reasearch pertaining to this abstract): Employment. Seal:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment.

Description: Background Beginning with the IFM 2005-04/MMVAR trial, three-drug combinations (TCs) have demonstrated superior clinical outcomes compared with two-drug regimens among patients with RRMM (Garderet JCO 2012). TCs are emerging as the standard of care at first relapse. We assessed factors that influenced treatment choice with TCs in a cohort of patients with RRMM who were managed in routine care. Methods We identified adult patients with MM between January 2008 and February 2014 in a large, national, US healthcare claims database of commercially insured and Medicare Advantage beneficiaries. Newly diagnosed patients were followed from the first claim with an ICD-9 code for MM (with a 12-month wash-out period). To ensure completeness of claim history, patients with continuous enrollment from 12 months pre-diagnosis through at least initiation of second-line therapy (SLT) for RRMM were included. Those with claims for transplants were excluded. Front-line therapy (FLT) began with the first claim for MM-directed systemic cancer therapy. Unique agents administered within 90 days of FLT initiation constituted a regimen. Continuation of FLT regimen (or part thereof) or monotherapy within 3 months of the end of the initial regimen was considered part of FLT. SLT after first relapse for RRMM was identified accordingly: 1) a treatment gap 〉6 months between end of FLT and start of a second regimen (retreatment or switch), 2) start of a follow-up regimen (retreatment) with a treatment gap of 〉3 and up to 6 months after end of FLT, or 3) a switch to another drug combination after FLT regimen. The first claim for SLT was the index date. SLT ended at the earliest of: start of a new drug, death, or end of study period (February 2014). Patients were grouped into those receiving one-/two-(1-2) vs three-/four-drug (3+) combinations based on the number of unique cancer therapy agents received within the start and end date of SLT. A logistic multivariable model was used to identify factors independently associated with receipt of 1-2 vs 3+ SLT regimens. Results Baseline characteristics among 249 RRMM patients on SLT are shown in Table 1 according to receipt of 1-2 vs 3+ SLT regimens. Among 62 patients who initiated SLT in 2013-14, 14 (23%) received a 3+ SLT regimen (vs 19 (10%) prior to 2013). Adjusting for gender and CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone disease), predictors of 3+ SLT included: younger age (

Description: Background Few studies have assessed HRU and costs in RRMM. A prior study reported 1-yr total healthcare costs of $113,000 (2013 US $) among non-transplant patients with newly diagnosed MM (DaCosta Byfield ASCO 2015). Real-world data on economic burden in the era of new MM therapeutic options could provide insight for directing efficient resource utilization. We examined HRU and costs associated with second-line therapy (SLT) in RRMM. Methods We identified adult pts with MM between Jan 2008 and Feb 2014 in a large, national, healthcare claims database of commercially insured and Medicare Advantage beneficiaries. Newly diagnosed pts were followed from first claim for MM (+12-mo wash out period). Pts with continuous enrollment from 12 mos pre-diagnosis through 12 mos post-initiation of SLT for RRMM were included (including pts who died within 12 mos post SLT start). Those with a claim for transplants were excluded. Front-line therapy (FLT) began with the first claim for MM-directed systemic cancer therapy. Unique agents administered within 90 d of FLT initiation constituted a regimen. Continuation of FLT regimen (or part thereof) or monotherapy within 3 mos of the end of the initial regimen was considered part of FLT. SLT after first relapse for RRMM was identified accordingly: 1) a treatment gap 〉6 mos between end of FLT and start of a 2nd regimen (retreatment or switch), 2) start of a follow-up regimen (retreatment) with treatment gap 〉3 and ≤6 mos after end of FLT, or 3) a switch to another drug combination after FLT. The first claim for SLT was the index date. Healthcare costs and HRU were determined for the 1-yr period following SLT start. Healthcare costs were calculated as total reimbursed amount to the provider paid by the health plan, the pt, and other payers, including treatment with subsequent lines of therapy if falling within the 1-yr period. Drug and drug-administration costs were captured from a) all pharmacy claims for MM-directed systemic therapy, and b) medical claims with CPT codes indicating chemotherapy drug administration if, on the same date of service, there was a claim with a HCPCS for any drug of interest. Results We identified 160 of 249 pts receiving SLT. The majority (55%) were female, 72% were aged ≥65 yrs, 10% received triplet SLT, and 53% were enrolled in a Medicare Advantage plan. Most common SLT regimens were bortezomib- (39%) or lenalidomide-based (38%) (Table 1). RRMM pts averaged 58 ambulatory visits and 1.2 hospitalizations in the yr following start of SLT, with 5.1 ICU and 7.9 non-ICU days. Mean 1-yr healthcare costs were $123,922 with 59% of total costs attributable to non-drug costs (mean: $72,718; Table 2). Conclusions The healthcare and economic burden of illness among pts with RRMM receiving SLT is substantial. The main cost driver in RRMM was non-drug related. While this research did not examine indirect costs, rates of ambulatory visits and hospitalization days occurring within 1 yr of the start of SLT were high and likely correlated with indirect costs to both the pt and caregiver. New treatment options with a more favorable side-effect and efficacy profile may mitigate this burden. At study completion, a statistical analysis will be conducted to assess the determinants and drivers of economic burden in RRMM. Table 1. RRMM pt Characteristics and SLT patterns Total (N=160)n (%)* Died during 1-yr following start of SLT 36 (22.5) Age, yrs