Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Post-Hoc Analysis of Sustained Undetectable Measurable Residual Disease (MRD)
High-Risk Smoldering Myeloma (SMM) is an asymptomatic plasma cell disorder with heterogeneous clinical behavior and once R-based regimens have shown to be effective in high-risk SMM patients, our next step was to perform this phase 2 trial, but aiming at abrogating the risk of progression through an intensive treatment regimen with the end point of achieving sustained MRD negativity (MRD-ve) at 3 and 5 years after ASCT.
Ninety SMM pts at high-risk of progression (>50% at 2 years), younger than 70 years and transplant candidates were included. Induction therapy consisted of six 4-weeks cycles of KRd in which carfilzomib (K) was given at dose of 36 mg/m2 twice per week plus lenalidomide (R) at dose of 25 mg on days 1-21 and dexamethasone (d) at dose of 40 mg weekly. Melphalan at dose of 200 mg/m2 followed by ASCT was given as intensification therapy followed by two KRd consolidation cycles and maintenance with R at dose of 10 mg plus dexamethasone at dose of 20 mg weekly for up to 2 years. The primary end-point was to evaluate the MRD-ve rate by next generation flow (NGF) after ASCT and MRD-ve rate maintained at 3 and 5 years after ASCT. Because of the COVID-19 pandemic, the MRD evaluation 3 years after ASCT was done in less patients than expected and we amended the protocol to evaluate sustained MRD-ve rate at 4 and 5 years.
Twenty-three percent of high-risk SMM treated with this curative strategy maintained MRD-ve 4 years after ASCT and 2 years after finalizing the treatment protocol. Progression to MM as well as biochemical progression were driven by the persistence of MRD at the end of maintenance and by lack of sustained MRD-ve 4 years after ASCT (2 years after the end of maintenance).
ASH 2022: Abstract #118
Maria-Victoria Mateos, MD, Joaquín Martínez-López, MD, PhD, Paula Rodríguez-Otero, MD, PhD, Jesús San-Miguel, MD, PhD, Veronica Gonzalez-Calle, MD, PhD, Marta Sonia Gonzalez, MD, Albert Oriol, MD, Norma C. Gutierrez, Rafael Rios, MD, PhD, Laura Rosinol Dachs, Miguel Angel Alvarez, MD, Joan Bargay, MD, PhD, Ana Pilar Gonzalez, PhD, Fernando Escalante, MD, Adrian Alegre, MD, PhD, Belén Iñigo, MD, Javier de la Rubia, MD, Ana Isabel Teruel, MD, Felipe De Arriba, PhD, Luis Palomera, MD, PhD, Miguel-Teodoro Hernández, MD, PhD, Javier Lopez Jimenez, MD, PhD, Marta Reinoso Segura, Aránzazu García Mateo, PhD, Enrique M. Ocio1, Joan Bladé, MD, PhD, Juan-José Lahuerta, MD, PhD, María Teresa Cedena, MD, PhD, Noemi Puig, MD, PhD and Bruno Paiva
Doctor Bio:
Maria-Victoria Mateos, MD, PhD is Consultant Physician in the Haematology Department and Associate Professor of Medicine at the University of Salamanca, Spain. She is the director of the Myeloma Program and coordinates the Clinical Trials Unit in Salamanca’s University Hospital Haematology Department.
