NEW YORK (Reuters Health) – In patients with newly diagnosed multiple myeloma, adding daratumumab to proteasome-inhibitor-based triple therapy is associated with high rates of minimal residual disease (MRD) negativity and excellent progression-free survival, according to a small nonrandomized pilot study.
“These unprecedented results were found in the absence of autologous bone marrow transplant,” Dr. Ola Landgren of the University of Miami, in Florida, told Reuters Health by email.
He and his colleagues treated 41 evaluable patients (median age, 59 years) with daratumumab added to weekly dosing of the second-generation proteasome-inhibitor carfilzomib with lenalidomide and dexamethasone (KRd). None received high-dose melphalan chemotherapy or autologous hemopoietic cell transplant.
In some prior studies, Dr. Landgren noted, “KRd has been given together with significant overhydration which caused congestive heart failure. Also, the use of weak anticoagulation has been associated with thrombosis. Here, weekly KRd with daratumumab, coupled with modern oral anticoagulation and limited IV fluids, resulted in minimal cardiovascular events. This study emphasizes the importance of paying close attention to details in practical clinical management, in addition to the actual drug.”
Median follow-up was for 20.3 months and the primary endpoint (MRD negativity in the bone marrow) was achieved in 29 of the patients (71%) over a median of six cycles.
At 11 months of median follow-up, the one-year progression-free survival rate was 98% and the overall survival rate was 100%. Serious adverse events, including neutropenia, associated with therapy were reported in eight patients, but there were no deaths.
Dr. Landgren concluded, “This is the most effective, modern combination therapy we have seen in patients with newly diagnosed multiple myeloma. These results strongly support the emerging trend of using modern 4-drug combination therapy and delayed autologous bone marrow transplant in patients with newly diagnosed multiple myeloma.”
In light of these results the researchers are currently enrolling a projected 462 patients into an open-label randomized study of this approach versus standard of care.
The study received support from Janssen, which sells daratumumab under the brand name Darzalex, and Amgen Pharmaceuticals. Dr. Landgren and several coauthors report financial ties to the companies.
Source: https://bit.ly/3tGeqIs JAMA Oncology, online April 15, 2021.
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