Multidrug/Transplant Protocol for High-Risk Smoldering Myeloma
Posted: Wednesday, April 22, 2020
Using the word “cure” as synonymous with “sustained minimal residual disease (MRD) negativity at 5 years after high-dose therapy–autologous stem cell transplantation (HDT-ASCT),” a team led by Maria-Victoria Mateos, MD, PhD, of the University of Salamanca, Spain has published in the journal Blood the results to date of their ongoing phase II, single-arm study of a specific drug/transplant protocol in high-risk smoldering myeloma.
“Our aim was to increase the MRD-negative rate from 34% (reported in newly diagnosed patients with multiple myeloma after bortezomib, thalidomide, and dexamethasone and ASCT) to at least 50%,” explained Dr. Mateos and colleagues. The primary endpoint was evaluation of the MRD-negative rate by next-generation flow cytometry after induction therapy and ASCT.
A total of 90 patients with smoldering myeloma, all transplant candidates up to age 70 who were considered to be at high risk of progression to active multiple myeloma, were recruited between June 2015 and June 2017; 11 discontinued for various reasons early on. As of February 2019, at a median follow-up of 32 months, 93% of patients remained alive and free of disease progression. Of the original 90 patients, 32% had “at least one of the new biomarkers predicting imminent risk of progression to multiple myeloma,” noted the researchers. However, “56% of the patients who completed induction and HDT-ASCT achieved MRD negativity,” which met the team’s stated aim.
Induction therapy consisted of six 4-week cycles of carfilzomib, lenalidomide, and dexamethasone (KRd). “Melphalan, followed by ASCT, was given as intensification therapy,” described Dr. Mateos and co-investigators. This was followed by two KRd consolidation cycles and then, for up to 2 years, by maintenance therapy with lenalidomide/dexamethasone.
At various points, relatively small numbers of patients developed grade 3 or 4 toxicities. They included neutropenia, thrombocytopenia, infections, skin rash, and hypertension.
Disclosure: The study authors’ disclosure information can be found at ashpublications.org.
