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

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 (<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.

Conclusions

A 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.