A combination of Kyprolis (carfilzomib), Revlimid (lenalidomide), and dexamethasone, given before and immediately after a stem cell transplant, is effective for the treatment of patients with smoldering multiple myeloma — a precursor condition to multiple myeloma — at high risk of progressing to the full blown disease, new clinical trial results suggest.
The data will be presented today at the American Society of Hematology (ASH) 2019 Annual Meeting in a presentation, titled “Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Followed By HDT-ASCT, Consolidation with Krd and Maintenance with Rd.”
Smoldering multiple myeloma is a condition that, while not itself symptomatic or dangerous, often progresses to active multiple myeloma. Previous research has tried to identify which smoldering multiple myeloma patients are most likely to progress, as treating people with these earlier conditions could be life-saving.
High-dose chemotherapy followed by a stem cell transplant is a standard-of-care treatment for myeloma. The basic idea is to take healthy bone marrow stem cells — the cells responsible for producing all the cells in blood — from a person. Then, the high-dose therapy wipes out blood cells (including the myeloma cells) en masse. The healthy stem cells can then be re-introduced; theoretically, they can repopulate the blood with only non-cancer cells.
The effects of this approach, however, can be augmented by giving the patient additional therapy before and after the procedure, termed induction and consolidation therapy.
The ongoing GEM-CESAR Phase 2 clinical trial (NCT02415413) is evaluating a combination of Kyprolis, Revlimid, and dexamethasone as induction and consolidation therapy for stem cell transplants. These agents act through different mechanisms, but the ultimate aim is to kill blood cells, particularly myeloma cells.
The trial included 90 patients with high-risk smoldering multiple myeloma. Patients were treated with the triple combination in six 4-week cycles, followed by high-dose melphalan and stem cell transplant, then another two cycles of the Kyprolis combo. Maintenance therapy with Revlimid and dexamethasone, at lower doses, was continued for up to an additional two years.
As of February 2019, after a median follow-up of 32 months, seven participants had completed treatment, 71 were receiving maintenance therapy, and 11 had discontinued (for reasons including disease relapse, adverse events, and death).
The treatment was effective, with 41% of patients being free of precursor myeloma cells after the induction treatment, a number that rose to 59% after the transplant, and later to 70% after consolidation therapy.
In total, 98% of participants remained alive, and 93% were both alive and free of disease progression.
Additionally, minimal residual disease (MRD) status — the presence of very small numbers of myeloma cells that remain after treatment and may cause relapse — was negative for more than half (56%) of patients who completed the transplant. This was a significant improvement from the 34% reported in patients with overt multiple myeloma receiving a transplant after Velcade (bortezomib), thalidomide, and dexamethasone.
While in the first presentation at the ASH meeting, researchers used flow cytometry — a technique that examines physical and chemical characteristics of single cells in a sample — to measure MRD status, in a separate presentation, they used a technique called quantitative immunoprecipitation mass spectrometry, which looks at proteins in the blood in great detail.
The researchers found that the techniques agreed in 81% of cases after induction, 70% after the transplant, and 68% after consolidation. This relatively high concordance suggests that both techniques may be useful in tracking disease progression in smoldering multiple myeloma, though further research will be needed to fully understand these relationships.