C061 | CARFILZOMIB INDUCTION, CONSOLIDATION, AND MAINTENANCE WITH OR WITHOUT AUTOLOGOUS STEM-CELL TRANSPLANT: LONG-TERM FOLLOW-UP OF THE RANDOMISED, PHASE 2 FORTE TRIAL

Background The randomised UNITO-MM-01/FORTE trial showed that carfilzomib-lenalidomide-dexamethasone (KRd) plus autologous stem cell transplant (KRd-ASCT) improved progression-free survival (PFS) compared to 12 KRd cycles (KRd12) and KCd-ASCT in transplant eligible (TE) newly diagnosed multiple myeloma (NDMM) pts. Lenalidomide (R) maintenance until progression combined with 2-year carfilzomib therapy (KR) improved 3-year PFS vs R alone. Patients and Methods 474 patients were randomized (R1) in one of the induction–intensification–consolidation arms (KRd-ASCT, n=158; vs KRd12, n=157; vs KCd-ASCT, n=159) and then (R2) into one of the maintenance arms (KR, n=178; vs R, n=178). The primary objectives of this updated analysis were to assess PFS, time to next therapy (TTNT), PFS after the next line of treatment (PFS2) and overall survival (OS), with extended follow-up (FU) . Secondary objectives included safety outcomes, with a focus on secondary primary malignancies (SPMs). Data cut-off was December 1st, 2024. Results The median (FU) from R1 was 93.6 months (mo). Median PFS from R1 was 99 mo with KRd-ASCT, significantly longer than KRd12 (70 mo; HR 0.73; p=0.04) and KCd-ASCT (64 mo; HR 0.65; p=0.005). Median TTNT was not reached (NR) in the KRd-ASCT arm vs 70 mo with KRd12 (HR 0.59; 0=0.002) and 87 mo with KCd-ASCT (HR 0.63; p=0.006). KRd-ASCT also demonstrated a trend towards superiority in PFS2 vs KRd12 (HR 0.71; p=0.07) and KCd-ASCT (HR 0.72; p=0.09). 8-years OS was similar in the 3 arms (75% vs 72% vs 68%). Median FU from R2 was 82 mo. Despite stopping K after 2 years in KR arm, and continuing with R alone only in both arms, there was a significant PFS benefits of KR vs R up to 4 years from R2 (4-year PFS 75% vs 66%; HR 0.66; p=0.04); after 4 year, the benefit diminishes over time (median PFS NR vs 88 mo; Figure). SPMs occurred in 30 pts (6%), of whom 19 had been exposed to ASCT (median time to onset 52 mo from R1);8 pts developed hematologic tumors, 19 solid tumors, 3 skin cancers. The relative incidence of SPMs was higher in KRd-ASCT pts (vs KRd12: 1.99; vs KCd-ASCT: 1.48). Ten pts died from SPMs, 6 treated with KRd-ASCT and still in remission. Conclusion With long-term FU, KRd-ASCT showed a median PFS of about 8 years, confirming superiority vs KRd12 and KCd-ASCT. The addition of K to R for up to 24 mo provided superior PFS benefits vs R alone, benefit retained for up to 2 years after stopping K. SPMs incidence was 6%, mainly in pts who underwent ASCT.