KEY TAKEAWAYS
- The phase 2 EMN19 study aimed to evaluate the interim efficacy and safety of daratumumab (Dara) plus bortezomib, cyclophosphamide, and dexamethasone in patients.
- The study included 40 patients, with the majority being NDMM (73%) and having International Staging System (ISS) stage II disease (83%).
- The study demonstrated that DaraVCD treatment effectively achieved significant MRD negativity and CMR rates.
Multiple myeloma (MM) with extramedullary disease (EMD) is an aggressive disease that necessitates the development of novel treatment strategies. To present interim efficacy/safety results of daratumumab (Dara) plus bortezomib (V), cyclophosphamide(C), and dexamethasone (D) in patients with multiple myeloma (MM) and early-stage multiple myeloma (EMD).
EMN19 (NCT04166565) is an ongoing, multinational, phase 2, open-label study involving patients with multiple myeloma (MM) who manifest with EMD. Patients were administered Dara (16 mg/kg IV/ 1800mg SC, weekly in C1–2, Q2W in C3–6, and Q4W in C7+) in conjunction with VCD and autologous stem cell transplantation (ASCT) until progression or for a maximum of 36 months.
Using EuroFlow Next Generation Flow cytometry, circulating tumor cells (CTC) in blood were quantified at baseline. About 40 patients (median age: 58; male: 22 [55%]; NDMM: 29 [73%]; RMM: 11 [28%]) were observed for a median of 19 months. At baseline, 33 (83%) patients were at International Staging System (ISS) stage II, while 6 (15%) met IMWG criteria for high risk. Patients with one extramedullary plasmacytoma (EMP), para osseous plasmacytoma (PO), or both were 22 (55%); the median number of plasmacytomas per patient was 2. At the endpoint, 19 (48%) patients were receiving treatment, while 21 (53%) had discontinued (progressive disease: 13 [33%] patients; mortality or inadequate response at the end of C3: 3 [8%] patients, each reason). Ten (25%) points were awarded ASCT. Only 1 patient (3%) with NDMM and 16 patients (40%; NDMM: 14; RMM: 2) achieved CR; 14 patients achieved CR without or before ASCT. Very excellent partial response (VGPR) was observed in 9 (23%) patients with NDMM, 4 (10%) patients with RMM, and 2 (5%) patients with NDMM. The median response time was four weeks. The median overall survival (OS) was not reached (NR; 11 fatalities), and the median progression-free survival (PFS) was 20 months (NDMM: NR; RMM: 15 months, P = 0.216). VGPR responses were associated with NDMM vs. RMM (24/29 [83%] vs. 6/11 [55%] pts, P=0.103) and 1 vs.>1 plasmacytomas at baseline (16/18 [89%] vs. 14/22 [62%] pts, P=0.082). 13 (76%) of 17 patients assessed for minimal residual disease (MRD) were MRD-negative, including 2 (12%) patients with VGPR response.
About 14 (78%) of 18 patients evaluated for EMD response had a complete metabolic response (CMR); 5 had CMR before CR, and 2 did not yet have CR. Despite the pandemic, no safety signals were found. CTC (median level: 0.002%; range: 0-0.35%) was detectable in 26 of 38 evaluable cases (median level: 0.002%; content: 0-0.35%). Detectable CTC levels were more common in patients with ISS II/III than in those with ISS I (I: 9/17 [53%] pts, II: 11/14 [79%] pts, III: 6/7 [86%] pts) and were comparable between PO only and EMP patients. VGPR rate was similar in patients with and without detectable CTC (21/26 [81%] and 8/12 [67%] patients, P=0.423).
DaraVCD treatment has obtained 43% CR and a median PFS of 20 months in patients presenting with ND EMD after a median FU of 19 months. NDMM and fewer plasmacytomas were associated with increased VGPR response rates and longer PFS. DaraVCD was efficacious regarding significant MRD (-) and CMR rates. According to the researcher, this is the first report on CTC in EMD, and they discovered a positive correlation between CTCs and ISS. This protocol may be an alternative for this high-risk, unmet-need population if the level of current responses is comparable to the results of the LYRA study, which included a similar DaraVCD protocol.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04166565
Meral Beksac, Tulin Tuglular, Francesca Gay, Roberto Mina, Eirini Katodritou, Ali Unal, Michele Cavo, Guner Hayri Ozsan, Vincent H.J. van der Velden, Berna Beverloo, Michael Vermeulen, Mark van Duin, Guldane Cengiz, Omur Gokmen Sevindik, Serena Merante, Kyriaki Manousou, Pieter Sonneveld, Evangelos Terpos/EFFICACY OF DARATUMUMAB PLUS BORTEZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN PATIENTS WITH MULTIPLE MYELOMA PRESENTING WITH EXTRAMEDULLARY DISEASE: A EUROPEAN MYELOMA NETWORK STUDY (EMN19)/Inc, M. G. (n.d.). EFFICACY OF DARATUMUMAB PLUS BORTEZOMIB, CYCLOPHOSPHAMIDE AND… by Prof. Meral Beksac. Library.ehaweb.org. Retrieved July 14, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386701/meral.beksac.efficacy.of.daratumumab.plus.bortezomib.cyclophosphamide.and.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178.
