ATLANTA – Daratumumab monotherapy led to durable partial responses among intermediate to high-risk patients with smoldering multiple myeloma, according to results from the phase II CENTAURUS trial.
Although less than 5% of patients had complete responses, 27% had at least a very good partial response to long-term therapy (up to 20 treatment cycles lasting 8 weeks each),, of the Ohio State University Comprehensive Cancer Center, Columbus, said at the annual meeting of the American Society of Hematology. The coprimary endpoint, median progression-free survival, exceeded 24 months in all dose cohorts, and was the longest when patients were treated longest.
Current guidelines recommend monitoring smoldering multiple myeloma every 3-6 months and treating only after patients progress. However, some experts pursue earlier treatment in the premalignant setting.
In, 123 adults with smoldering multiple myeloma were randomly assigned to receive daratumumab (16 mg/kg IV) in 8-week cycles according to a long, intermediate, or short/intense schedule. The long schedule consisted of treatment weekly for cycle 1, every other week for cycles 2-3, monthly for cycles 4-7, and once every 8 weeks for up to 13 more cycles. The intermediate schedule consisted of treatment weekly in cycle 1 and every 8 weeks for up to 20 cycles. The short, intense schedule consisted of weekly treatment for 8 weeks (one cycle). Patients were followed for up to 4 years or until they progressed to multiple myeloma based on International Myeloma Working Group guidelines.
Over a median follow-up period of 15.8 months (range, 0 to 24 months), rates of complete response were 2% in the long treatment arm, 5% in the intermediate treatment arm, and 0% in the short treatment arm. Rates of at least very good partial response were 29%, 24%, and 15%, respectively. Overall response rates were 56%, 54%, and 38%, respectively. Median PFS was not reached in any arm, exceeding 24 months.
Treatment was generally well tolerated, said Dr. Hofmeister. The most common treatment-related adverse effects were fatigue, cough, upper respiratory tract infection, headache, and insomnia. Hypertension and hyperglycemia were the most common grade 3-4 treatment-emergent adverse events, affecting up to 5% of patients per arm. Fewer than 10% of patients in any arm developed treatment-emergent hematologic adverse events, and fewer than 5% developed grade 3-4 pneumonia or sepsis. There were three cases of a second primary malignancy, including one case of breast cancer and two cases of melanoma.
Rates of infusion-related reactions did not correlate with treatment duration. Grade 3-4 infusion-related reactions affected 0% to 3% of patients per arm. The sole death in this trial resulted from disease progression in a patient from the short treatment arm. “Taken together, efficacy and safety data support long dosing compared to intermediate and short dosing,” Dr. Hofmeister said.
The three arms were demographically similar. Patients tended to be white, in their late 50s to 60s, and to have ECOG scores of 0 with at least two risk factors for progression. About 70% had IgG disease and nearly half had less than 20% plasma cells in bone marrow.
Janssen, the maker of daratumumab, sponsored the trial. Dr. Hofmeister disclosed research funding from Janssen and research support, honoraria, and advisory relationships with Adaptive Biotechnologies, Thrasos, Celgene, Karyopharm, Takeda, and other pharmaceutical companies.
SOURCE: Hofmeister C et al, ASH 2017,