P963: evolution of treatment patterns and overall survival in patients with relapsed/refractory multiple myeloma receiving a second line of therapy between 2012 and 2020: analysis of the preamble cohort

Background: Treatment (Tx) options such as immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and more recently anti-CD38 monoclonal antibodies (mAbs) have improved clinical outcomes for patients (pts) with multiple myeloma (MM); yet many experience disease relapse or become refractory to Tx. PREAMBLE is a prospective, observational cohort study of pts with MM in North America and Europe. Aims: To assess Tx patterns and overall survival (OS) evolution over time in pts with relapsed/refractory MM (RRMM) who received a second-line therapy (2L) between 2012 and 2020 in the PREAMBLE study. Methods: This analysis focused on a subset of pts enrolled in PREAMBLE at the time of initiating 2L Tx for MM. The index date was defined as the enrollment date. Pts were followed until death, completion of 3 years of follow-up (FU), date of loss to FU, or date of last visit prior to database extraction date. Pt characteristics, previous Tx since diagnosis and 2L regimens received were described at index date. Pts were grouped by date of enrollment in 3 cohorts (2012-15, 2016-18, and 2019-20). Duration of 2L Tx and OS were analyzed using the Kaplan Meier method. Results: 611 pts were included with a median age of 71 years at the start of 2L Tx, 56.8% were male, and 72.7% and 27.3% were from Europe and North America, respectively. 352 pts received 2L in 2012-2015, 199 in 2016-2018 and 60 in 2019-2020. Median FU was 22.8, 32.3 and 18.4 months in the 3 cohorts. The median time from diagnosis to the start of 2L Tx was 33.3 months, increasing from 31.8 months in the 2012-15 cohort to 40.2 months in the 2019-20 cohort. Prior to the study entry, during first line (1L), 31.6% of pts received a stem cell transplant (SCT) (34.9%, 27.6% and 25.0% respectively for the 3 cohorts). Overall, the main 1L regimens received were PI-based regimens (48.0%), IMiD-based regimens (24.9%), and combinations of IMiD and PI (22.7%). Fewer than 5 pts received an anti-CD38 mAb in 1L. The proportion of pts who received a combination of IMiD and PI in 1L increased from 19.3% in 2012-15 to 25.1% in 2016-18 and 35.0% in 2019-20. Regarding 2L Tx received, single class regimens (IMiD only and PI only) use dropped from 88.0% in 2012-15 to 62.8% in 2016-18 and 18.4% in 2019-20. It was replaced by various combinations of Tx as shown in the figure. The combinations of Tx containing anti-CD38 mAb had increased from 9.0% to 60.1% since the first launch of anti-CD38 in 2016. 9.0% of pts received an SCT during 2L (10.5%, 8.0% and 3.3% for the 3 cohorts). The unadjusted median duration of 2L for the 3 cohorts was of 6.0, 8.1 and 9.9 months (log rank test, p=0.01). A significant improvement in unadjusted OS was observed (log rank test, p<0.001). One year-OS (95% confidence interval [CI]) was 78.4% (73.9-82.9), 84.8% (79.7-89.9) and 93.0% (86.3-99.7); 2 year-OS (95%CI) was 61.3% (55.8-68.5), 74.5% (68.2-80.6) and 77.7% (65.0-90.4) in 2015-16, 2016-18 and 2019-20 cohorts, respectively. Median OS was not reached. Image:Summary/Conclusion: Major changes in 2L Tx patterns were observed in pts with RRMM between 2012 and 2020 with the decreased use of single class regimens and the increased use of combination Tx. Pts were likely to be exposed to all 3 main classes of drugs (IMiD, PIs and anti-CD38) earlier in the Tx pathway. A trend towards improvement in OS from start of 2L was also observed over time, likely driven by the changes in Tx patterns. Future analyses of this on-going study will allow to evaluate the long-term impact of those new Tx and the remaining unmet needs.