P-109: Carfilzomib-Lenalidomide-Dexamethasone Vs. Lenalidomide-Dexamethasone in Non-Frail Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma: The EMN20 Trial

Introduction: Trial in Progress (TiP). Prior to the recent introduction of daratumumab (Dara) in the frontline setting, lenalidomide-dexamethasone (Rd) has represented a standard of care for transplant-ineligible (NTE) patients (pts) with newly diagnosed multiple myeloma (NDMM). Nonetheless, median progression-free survival (PFS) with Rd was still limited, as compared with 3/4-drug regimens, also including carfilzomib (K). The randomized, multicenter phase III EMN20 trial (NCT04096066) compares KRd vs Rd in fit/intermediate-fit NDMM pts according to the International Myeloma Working Group frailty score.

Methods: NTE NDMM pts were randomized to KRd (28-day cycles, once-weekly K 56 mg/m² on days 1,8,15 for 12 cycles and on days 1,15 from cycle 13 onwards, R 25 mg orally on days 1-21 and d 40 mg on days 1,8,15,22) or continuous Rd (28-day cycles, R 25 mg on days 1-21, d 40 mg on days 1,8,15,22). Pt stratification was based on International Staging System (ISS) stage and fitness status. After 5 years, pts in the KRd arm will stop K administration and continue Rd, except for pts achieving sustained minimal residual disease (MRD) negativity after 2 years, who will stop K administration after 2 years and continue Rd. The primary endpoints were MRD after 2 years of treatment and PFS. For MRD assessment, the clonoSEQ® assay was used at the sensitivity of ≥10⁻⁵. The MRD negativity rate was the proportion of MRD-negative pts (sensitivity ≥10⁻⁵) at 2 years of treatment. Key secondary endpoints included response rates, overall survival and safety. On Nov 23, 2021, the protocol was prematurely stopped after the introduction of frontline Dara-Rd. Here we report the demographics of the enrolled pts.

Results: A total of 101 pts were enrolled and 82 were randomized (KRd 42 vs Rd 40); 19 pts were not randomized due to screening failure (17) and withdrawal of consent (2). Pt characteristics were well balanced between the KRd and Rd arms: median age was 73 (interquartile range [IQR] 70–76) and 74 years (IQR 72–76), 60% vs 58% of pts were fit, 40% vs 42% were intermediate fit, 33% vs 30% had ISS stage III disease, 17% vs 8% had Revised ISS III, 10% vs 3% had Eastern Cooperative Oncology Group (ECOG) Performance Status 2 and 22% vs 22% had high-risk cytogenetics, respectively. Median follow-up was 23 months (IQR 19–28). In the KRd vs Rd arms, 33/42 (78.6%) vs 19/40 (47.5%) pts are still under treatment; reasons for discontinuation were medical decision (1 vs 4), death (2 vs 4), adverse events (2 vs 1), progressive disease (3 vs 10), lost to follow-up (1 vs 0) and consent withdrawal (0 vs 2).
The analysis of the primary MRD endpoint is planned for Q4 of 2023, after all pts have received 2 years of treatment.

Conclusions: Data about MRD will be presented at the meeting.