Introduction: Many new treatments and combinations have emerged over the last decade to treat relapsed or refractory multiple myeloma (RRMM). Treatment strategies include doublet and/or triplet combinations from the following classes of agents: immunomodulatory drugs, proteasome inhibitors, and recently approved immuno-oncology agents. Combinations with new agents like pomalidomide, carfilzomib, ixazomib, elotuzumab, and daratumumab have demonstrated improved survival in RRMM in clinical trials, specifically with continued treatment until disease progression, with an acceptable safety profile (Lonial S et al. N Engl J Med 2015; Dimopoulos M et al. N Engl J Med 2016; Palumbo A et al. N Engl J Med 2016; Moreau P et al. N Engl J Med 2016; Stewart AK et al. N Engl J Med 2015; Dimopoulos M et al. Blood 2012). Median duration of treatment (DoT) was described in the literature as 12.4 wk for pomalidomide plus low-dose dexamethasone, 68 wk for ixazomib plus lenalidomide/dexamethasone, 74 wk for elotuzumab plus lenalidomide/dexamethasone, and 88 wk for carfilzomib plus lenalidomide/dexamethasone (Lonial S et al. N Engl J Med 2015; Moreau P et al. N Engl J Med 2016; Stewart AK et al. N Engl J Med 2015; Dimopoulos M et al. Blood 2012). The actual DoT of these agents in clinical practice settings is not known and it is unclear if DoT is affected by safety concerns and/or might have an impact on patient (pt) outcomes. Here we provide real-world evidence of DoT and time to next therapy (TTNT) with each of these agents in an attempt to understand their potential for durability of response and tolerability.
Methods: Analysis was conducted using the Explorys electronic medical records US database. Pts aged ≥18 y with ≥1 medical record with a diagnosis of MM (International Classification of Diseases [ICD], Ninth Revision, Clinical Modification diagnosis codes: 203.0x; ICD-10 codes: C90.0x) any time from January 1, 2010, preceded by ≥12 mo (baseline period) without a diagnosis of MM, were identified and followed longitudinally from their index diagnosis date (index date) through the course of available follow-up. A line of therapy (LoT) was defined as a drug/drug combination taken within a 28-d period from initiation of treatment course and ended upon cessation of those drugs, or at initiation of a drug not part of the current LoT. Pts with RRMM were identified as those who had ≥1 prior LoT. Demographic and baseline characteristics were analyzed using descriptive statistics. Distribution of treatment regimens in each LoT are reported; treatment cohorts are not mutually exclusive and LoTs containing multiple drugs are included in respective cohorts. Median DoT in each LoT and TTNT were estimated using descriptive and Kaplan-Meier analyses.
Results: 1745 LoTs were identified for 854 pts with RRMM (median age 66 y; 51% male; 37% had hypertension; 10% had chronic pulmonary disease at baseline). LoTs comprised pomalidomide (n=567 [32%]), carfilzomib (n=609 [35%]), ixazomib (n=172 [10%]), elotuzumab (n=76 [4%]), and daratumumab (n=321 [18%]). These agents were mostly used in later LoTs (mean number of prior LoTs, 3.7). Median (IQR) follow-up from index date was 39.4 mo (25.5-56.4) for these pts. Baseline characteristics were similar across treatment cohorts, although pts receiving ixazomib and carfilzomib presented with higher rates of hypertension and chronic pulmonary disease at baseline (Table). Mean/median DoT for pts with a second line (2L) of treatment and pts with ≥2L was longest for elotuzumab (8.7/4.4 mo and 5.3/2.7 mo, respectively). Kaplan-Meier estimates supported these findings (Table). Mean/median TTNT for pts with 2L or ≥2L was longest for elotuzumab (2L: 9.6/6.5 mo; ≥2L: 6.1/3.7 mo) and carfilzomib (2L: 8.7/6.2 mo; ≥2L: 7.3/4.7 mo).
Conclusions: Real-world evidence indicates that the new agents for RRMM-pomalidomide, carfilzomib, ixazomib, elotuzumab, and daratumumab-are used in later LoTs. DoT in clinical practice may be shorter than that reported in clinical trials. Rates of remaining on treatment were highest among pts treated with elotuzumab, suggesting that the longest durability of response observed with this immuno-oncology agent may be accompanied by acceptable tolerability despite longer exposure to treatment. Additional analyses and follow-up will determine whether longer DoT improves clinical outcomes.
Study support: Bristol-Myers Squibb.
Potluri: SmartAnalyst Inc.: Employment; Janssen: Consultancy, Research Funding. Kanakamedala: SmartAnalyst Inc.: Employment. Chen: Bristol-Myers Squibb: Employment. Yasenchak: Bristol-Myers Squibb: Consultancy; Seattle Genetics: Consultancy. Ranjan: SmartAnalyst India Pvt. Ltd: Employment. Papademetriou: SmartAnalyst Inc.: Employment. Bhandari: SmartAnalyst India Pvt. Ltd: Employment. Mann: SmartAnalyst India Pvt. Ltd: Employment. Davis: Bristol-Myers Squibb: Employment.
Asterisk with author names denotes non-ASH members.