Lisa Leypoldt, MD, discusses findings from the phase 2 GMMG-CONCEPT trial in patients with multiple myeloma.
Lisa Leypoldt, MD, clinician and researcher, Department of Oncology, Hematology and Bone Marrow Transplantation with Department of Pneumology, University Medical Center Hamburg-Eppendorf, and a postdoctoral research fellow, Dana-Farber Cancer Institute, discusses findings from the phase 2 GMMG-CONCEPT trial (NCT03104842) in patients with multiple myeloma.
The phase 2 trial evaluated the addition of isatuximab-irfc (Sarclisa) to carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Isa-KRd) in transplant-eligible (n = 127) and transplant-ineligible (n = 26) patients with newly diagnosed multiple myeloma with high-risk disease. High-risk disease was defined as having International Staging System stage II/III risk with deletion 17p, translocation (4;14), or translocation (14;16), or more than three 1q21 copies. Transplant-eligible patients received 6 cycles of Isa-KRd induction before transplant, followed by 4 cycles of Isa-KRd consolidation plus Isa-KR as maintenance therapy for 2 years. Transplant-eligible patients also received high-dose melphalan. Transplant-ineligible patients received an additional 2 cycles of Isa-KRd cycles during induction.
The primary end point of the study was minimal residual disease (MRD) negativity levels below 10−5 per next-generation flow at the end of consolidation. The secondary end point was progression-free survival (PFS), Leypoldt says.
Findings from the interim analysis demonstrated that the MRD-negativity rates after consolidation were 67.7% and 54.2% in transplant-eligible and transplant-ineligible patients, meeting the primary end point of the study, (P = .004; P = .012), respectively. Moreover, 81.8% and 69.2% of transplant-eligible and transplant-ineligible patients achieved MRD negativity at any time point, respectively, Leypoldt says. Moreover, MRD negativity was sustained for more than 1 year in 62.6% and 46.2% of transplant-eligible and transplant-ineligible patients, respectively.
Encouragingly, at a median follow-up of 44 months in transplant-eligible patients and 33 months in transplant-ineligible patients, median PFS and median overall survival were not reached in either arm, Leypoldt says. The 1-, 2-, and 3-year PFS rates were 86.4% (95% CI, 80.5%-92.6%), 78.3% (95% CI, 71.4%-85.9%), and 68.9% (95% CI, 61.2%-77.7%) in transplant-eligible patients and 75.1% (95% CI, 59.7%-94.5%), 62.6% (95% CI, 46.0%-85.3%), and 58.4% (95% CI, 41.7%-81.9%) in transplant-ineligible patients. These outcomes are promising for such a high-risk patient population, Leypoldt concludes.