Type: Eposter Presentation
Daratumumab (DARA) received FDA approval in November 2015 based on data from single-arm phase 2 studies, following fast track/breakthrough therapy designation based on preliminary clinical evidence showing substantial improvements over available therapy for the treatment of heavily pretreated/refractory patients with multiple myeloma (MM). Recent analyses of pooled DARA studies and real-world US data revealed median overall survival (OS) of 19.9 (95% confidence interval [CI], 15.1-not evaluable) months and 7.9 (95% CI, 6.9-8.9) months in heavily pretreated and refractory patients with MM, respectively (Usmani S, et al. Blood. 2015;126(23): Abstract 4498 and Usmani S, et al. Blood. 2015;126(23): Abstract 29). In the absence of randomized head-to-head trials, evidence on the relative treatment efficacy of DARA versus physician’s choice (PC) based on an adjusted comparison of data from a single arm trial versus a historical control group of comparable patients can inform the decisions of both clinicians and payers.
To estimate the comparative efficacy of DARA, as measured by overall survival, versus real-world historical control (PC) based on a comparison of data from DARA monotherapy clinical studies versus real-world US data, adjusted for confounding factors between patient cohorts.
Patient-level data were pooled from DARA monotherapy clinical studies (patients treated with DARA 16 mg/kg in the SIRIUS and GEN501 studies) and from two independent US databases (IMS-LifeLink and OPTUM), which reflect treatments utilized in a real-world cohort of patients with MM who received at least 3 prior therapy lines or were double refractory to a proteasome inhibitor and immunomodulatory drug. Using a multivariate proportional hazards regression model, the relative treatment effect of DARA compared with PC was estimated, adjusting for imbalances in patient characteristics between patient cohorts; co-variates included gender, age, albumin, hemoglobin, number of prior therapies, prior pomalidomide/carfilzomib-exposure, and refractory status.
Baseline characteristics that differed between patients treated with DARA (N=148) and the real-world US historical control (N=658) included median age (64 vs 69 y), median lines of prior therapy (5 vs 4), prior treatment with pomalidomide (55% vs 15%) and carfilzomib (41% vs 28%), and triple/quadruple refractory status (64% vs 14%). The adjusted OS-hazard ratio (HR) for DARA versus PC was 0.32 (95% CI, 0.22-0.46) compared with 0.44 (95% CI, 0.33-0.58) for unadjusted HR. The impact of adjustment was mainly driven by differences in refractory status and prior exposure to pomalidomide/carfilzomib.
This adjusted treatment comparison suggests that DARA demonstrates improved OS compared with real-world historical control data in heavily pretreated and refractory MM patients. Such comparisons allow evaluation of novel agents in the absence of head-to-head comparison studies.
Session topic: E-poster
Keyword(s): Multiple myeloma