P872: EFFICACY OF DARATUMUMAB PLUS BORTEZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN PATIENTS WITH MULTIPLE MYELOMA PRESENTING WITH EXTRAMEDULLARY DISEASE: A EUROPEAN MYELOMA NETWORK STUDY (EMN19) (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple myeloma (MM) with extramedullary disease (EMD) is an aggressive disease requiring novel treatment approaches. Aims: To present interim results on the efficacy/safety of daratumumab (Dara) plus bortezomib (V), cyclophosphamide (C) and dexamethasone (D) in patients (pts) with MM and EMD. Methods: EMN19 (NCT04166565) is an ongoing, multinational, phase 2, open-label study, among pts with MM (newly diagnosed MM [NDMM] or at first relapse [RMM]) presenting with EMD. Pts were given Dara (16 mg/kg IV/ 1800 mg SC, weekly in C1–2, Q2W in C3–6, and Q4W in C7+) combined with VCD until progression or max 36 months and autologous stem cell transplantation (ASCT). Responses were assessed according to IMWG and Impetus criteria (Zamagni, E. et al., 2021, DOI: 10.1200/JCO.20.00386). Circulating tumour cells (CTC) were quantified in blood at baseline by EuroFlow Next Generation Flow cytometry. Results: 40 pts (median age: 58 years; male: 22 [55%]; NDMM: 29 [73%]; RMM: 11 [28%]) were followed up for a median of 19 months. At baseline, 33 (83%) pts were at International Staging System (ISS) stage ≤II and 6 (15%) were at high-risk by IMWG criteria. Pts with ≥1 extramedullary plasmacytoma (EMP), paraosseous (PO) or both were 22 (55%), 14 (35%) and 4 (10%); the median number of plasmacytoma/pt was 2. At cutoff, 19 (48%) pts were on treatment and 21 (53%) discontinued (progressive disease: 13 [33%] pts; death or inadequate response at end of C3: 3 [8%] pts, each reason). Ten (25%) pts received ASCT. Stringent CR was achieved by 1 (3%) pt with NDMM and CR by 16 (40%; NDMM: 14; RMM: 2) pts; 14 pts achieved ≥CR without or prior to ASCT. Overall deepest responses were as follows: very good partial response (VGPR) by 9 (23%) pts with NDMM and 4 (10%) pts with RMM and PR by 2 (5%) pts with NDMM. Median time to first response was 4 weeks. Median OS was not reached (NR; 11 deaths occurred); median progression-free survival (PFS) was 20 months (NDMM: NR; RMM: 15 months, P: 0.216; Figure). ≥VGPR responses were associated with NDMM vs RMM (24/29 [83%] and 6/11 [55%] pts, p=0.103), and having 1 vs >1 plasmacytomas at baseline (16/18 [89%] and 14/22 [64%], p=0.082). Of 17 pts assessed for minimal residual disease (MRD), 13 (76%; NDMM: 11; RMM: 2) were MRD (-), including 2 (12%) pts with VGPR response. Of 18 pts assessed for EMD response, 14 (78%) had a complete metabolic response (CMR); 5 had CMR prior to CR and 2 had CMR without having achieved CR yet. No safety signals were detected despite the pandemic. CTC (median level: 0.002%; range 0-0.35%) was detectable at diagnosis in 26 out of 38 evaluable cases. Detectable CTC levels were more frequent in pts with ISS II/III compared to ISS I (I: 9/17 [53%] pts, II: 11/14, [79%] pts, III: 6/7 [86%] pts) and were similar between PO only and EMP pts. ≥VGPR rate was similar between pts with detectable and non-detectable CTC (21/26 [81%] and 8/12 [67%] pts, p=0.423). Summary/Conclusion: After a median FU of 19 months, DaraVCD treatment has been able to achieve 43% ≥CR and a median PFS of 20 months among pts presenting with ND EMD. NDMM and less number of plasmacytomas were associated with higher rates of ≥VGPR responses and better PFS. DaraVCD was effective in terms of substantial rates of MRD (-) and CMR. To our knowledge this is the first report on CTC in EMD and CTCs were found to be positively correlated with ISS. Based on the level of current responses approaching the results of the LYRA study which includes a similar DaraVCD protocol among NDMM, this protocol may be considered as an alternative for this high-risk population of unmet need. Figure 1. Progression-Free Survival by type of MMKeywords: Multiple myeloma