Sarclisa is first anti-CD38 to significantly improve progression-free survival in combination with VRd for newly diagnosed transplant-ineligible multiple myeloma in phase III

IMROZ is the first global phase III study of an anti-CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve PFS and show deep responses in this patient population who often have poor prognoses. The results were shared in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting and simultaneously published in the New England Journal of Medicine (NEJM).The use of Sarclisa in combination with VRd in transplant-ineligible NDMM is investigational and has not been fully evaluated by any regulatory authority.

Key Results: IMROZ is a global, randomized, multi-center, open-label study. At the data cut-off of September 26, 2023, through the median follow-up of 59.7 months, the following were observed for Sarclisa-VRd compared to VRd:  Primary endpoint: i. 40% reduction in the risk of disease progression or death for patients treated with Sarclisa-VRd versus VRd (HR 0.596; 98.5% CI: 0.406 to 0.876; p=0.0005). At the median follow-up of 59.7 months, the median PFS with the Sarclisa-VRd combination was not reached versus 54.3 months with VRd. ii. The estimated PFS at 60 months was 63.2% for patients treated with Sarclisa-VRd versus 45.2% for VRd.

Secondary endpoints: i. Approximately three-quarters (74.7%) of patients treated with Sarclisa-VRd achieved a complete response (CR) compared to 64.1% of patients taking VRd (OR 1.7; 95% CI: 1.097-2.5; p=0.008). ii. More than half (55.5%) of patients treated with Sarclisa-VRd achieved MRD negative CR compared to 40.9% of patients taking VRd (OR 1.8; 95% CI: 1.229-2.646; p=0.0013). iii. MRD was sustained for at least 12 months among nearly half (46.8%) of patients in the Sarclisa-VRd arm compared to less than one-quarter (24.3%) of patients taking VRd (OR 2.7; 95% CI: 1.799-4.141). At the date of data cut-off, 47.2% of patients (125/263) treated with Sarclisa-VRd and 24.3% of patients (44/181) treated with VRd were still on treatment. The median treatment duration for the Sarclisa-VRd combination was 53.2 months vs. 31.3 months for VRd.

The safety and tolerability of Sarclisa observed in this study was consistent with the established safety profile of Sarclisa-VRd with no new safety signals observed. Grade greater than 3 treatment-emergent adverse events (TEAE) occurred in 91.6% of patients taking Sarclisa-VRd and 84% of patients taking VRd. Treatment-emergent events (TAE) of any grade led to treatment discontinuation in 22.8% of patients taking Sarclisa-VRd and 26% of patients taking VRd.

See-"Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma"; Authors: Thierry Facon, M.D., Meletios-Athanasios Dimopoulos, M.D., Xavier P. Leleu, M.D., Meral Beksac, M.D., Ludek Pour, M.D., Roman Hájek, M.D., Zhuogang Liu, M.D., +23, for the IMROZ Study Group. Published June 3, 2024. DOI: 10.1056/NEJMoa2400712.