Predictors of Second-Line Treatment Choice with Triplet Therapy in Routine Care Among Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Abstract

BackgroundBeginning 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.MethodsWe 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.ResultsBaseline 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 (<65 years), early relapse (time to next therapy [TTNT], interval from start of FLT to start of SLT, <6 months), 3+ agents in FLT and index year of SLT initiation (in 2013-14). Charlson Comorbidity Index (CCI) was not independently associated with receipt of 3+ SLT.ConclusionsA majority of patients do not receive triplet-based SLT in routine care. Younger age, and not comorbidity status, appears to be the discriminatory patient characteristic for triplet therapy choice. Introduction of triplets with a favorable toxicity profile and assessment for comorbidity status in routine practice represent steps towards optimizing treatment choices in RRMM.Table 1Baseline Characteristics among Patients with RRMM According to SLT Type (N=249)N (%)Monotherapy/Doublet (1-2) (N=216)Triplet/Quadruplet (3+) (N=33)Total (N=249)TTNT<6 months44 (20.4%)14 (42.4%)58 (23.3%)≥6 months172 (79.6%)19 (57.6%)191 (76.7%)Age, years<6553 (24.5%)17 (51.5%)70 (28.1%)65-7464 (29.6%)8 (24.2%)72 (28.9%)≥7599 (45.8%)8 (24.2%)107 (43%)Male105 (48.6%)16 (48.5%)121 (48.6%)CCI060 (27.8%)10 (30.3%)70 (28.1%)152 (24.1%)3 (9.1%)55 (22.1%)2+104 (48.1%)20 (60.6%)124 (49.8%)CRAB symptoms147 (68.1%)26 (78.8%)173 (69.5%)Number of agents in FLT regimen1-2147 (68.1%)12 (36.4%)159 (63.9%)3+69 (31.9%)21 (63.6%)90 (36.1%)Table 2Predictors of 3+ SLT in RRMM (N=249)Odds Ratio (OR) for 3+ vs 1-2 SLT(95% CI for OR)Age, years<65 65-74 ≥753.10 1.36 Reference(1.13 - 8.51)* (0.45 - 4.09) -Male1.13(0.51 - 2.51)Index year2008-2012 ≥2013Reference 3.42- (1.42 - 8.21)**TTNT, months≥6 <6Reference 2.54- (1.05 - 6.17)*CRAB symptoms at baseline1.69(0.63 - 4.58)CCI0 1 2+Reference 0.41 0.98- (0.10 - 1.62) (0.39 - 2.46)Number of agents in FLT regimen1-2 3+Reference 2.77- (1.20 - 6.42)**significant at 5%; **significant at 1% DisclosuresRomanus:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Jhaveri:Takeda Pharmaceutical Company Limited: Equity Ownership; Sanofi: 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.