Analyses of Real World Data on Overall Survival in Multiple Myeloma Patients with at Least 3 Prior Lines of Therapy Including a PI and an IMiD, or Double Refractory to a PI and an IMiD

Background: To fully evaluate the potential benefit of novel agents for the treatment of patients with multiple myeloma (MM) who are heavily pretreated and refractory, it is important to understand the outcomes of this patient population based on current real-world experience. An International Myeloma Working Group study determined that the median overall survival (OS) of patients refractory to bortezomib (proteasome inhibitor, PI) and at least 1 immunomodulatory drug (IMiD) was 9 months (Kumar S et al. Leukemia 2012; 26: 149). Since then, other therapies have been approved for relapsed and refractory MM in the United States (US), including pomalidomide (IMiD) and carfilzomib (PI). In this analysis, real-world data were used to define the treatment landscape and outcomes of patients with MM refractory to PIs and IMiDs or who had received ³3 prior lines of therapy (LOT; including a PI and an IMiD) and provide context to results from the single-agent daratumumab phase 2 study MMY2002 (Sirius) recently presented at ASCO 2015 (Lonial S. J Clin Oncol 33, 2015 suppl; abstr LBA8512).

Methods: Two independent databases were analyzed. The IMS LifeLink: IMS Oncology Electronic Medical Records (EMR) Database (IMS Health Incorporated, Danbury, CT) and the OPTUM Database (OPTUM, Inc., Eden Prairie, MN) both comprised US patients only. For the IMS LifeLink database, patient records from the index period of 2000-2011 were screened. For the OPTUM database, the indexing period was 2007-2014. Median OS was assessed for cohorts that met the criteria of disease that was double refractory to a PI and IMiD (Criteria 1) or had been treated with ³3 LOT including a PI and IMiD and showed disease progression within 60 days on completion of last regimen (Criteria 2). Patients who met Criteria 1 could have received ³3 prior LOT, however those who met Criteria 2 only did not meet the double refractory criteria. Subgroup analyses of the eligible population were conducted on those who were only double refractory and triple/quadruple refractory.

Results: For the IMS LifeLink database, 4,030 patients with MM were screened, approximately 90% of patients were diagnosed with MM in 2006 or later, and 500 met the criteria for the target population. Of the 500 patients, 323 patients met Criteria 1 and 177 patients only met Criteria 2. For the OPTUM database, 3,837 patients with MM were screened, approximately 90% of patients were diagnosed after 2009, and 162 met the criteria for the target population, 120 of whom met Criteria 1 and 42 of whom only met Criteria 2. In the total eligible populations, median OS was 239 days in the IMS LifeLink dataset compared with 240 days in the OPTUM dataset (P = 0.5358). Among patients that were only double refractory (triple/quadruple refractory patients excluded), median OS was 228 days (n = 253) in the IMS LifeLink dataset compared with 259 days (n = 97) in the OPTUM dataset (P = 0.8052). In triple/quadruple refractory patients, median OS was 154 days (n = 70) in the IMS LifeLink dataset and 95 days (n = 23) in the OPTUM dataset (P = 0.6675). The results from both databases were consistent, hence the data were pooled for further analyses; the pooled analyses indicated that the median OS was 240 days for the eligible population (n = 662), 237 days for patients who were only double refractory (n = 350), and 154 days for patients who were triple/quadruple refractory (n = 93). A naïve comparison of the OS curves from the MMY2002 study and the pooled analysis suggests a survival benefit with daratumumab versus the real-world historical control (Figure).

Conclusions: Analyses of real-world data from two independent US patient databases indicated that outcomes remain poor among patients with MM who are heavily pretreated and/or highly refractory despite the availability and use of newer PIs and IMiDs, such as carfilzomib and pomalidomide. Median OS of approximately 8 months was observed in patients with ≥3 LOT (including a PI and IMiD) or refractory to a PI and IMiD. These data not only highlight the critical need for new MM treatments for patients with advanced MM, but also provide a point of reference against which novel agents such as daratumumab could be evaluated.