Results from a recent study of patients with relapsed/refractory multiple myeloma (MM) suggest that treatment with daratumumab may be associated with trends of improved bone turnover, although the results of the primary analysis were not statistically significant. The study results were reported in the journal Cancers (Basel).
Patients with MM may experience osteolytic bone disease that can accompany MM. Multiple treatments for MM can impact bone disease associated with MM, but the effects of CD38-targeting monoclonal antibodies, such as daratumumab, on bone metabolism have been unclear, the study investigators explained in their report.
In the noncomparative, open-label, prospective, multicenter phase 2 REBUILD trial, (ClinicalTrials.gov Identifier: NCT03475628), patients with relapsed/refractory MM with measurable disease were treated with daratumumab. Patients had previously received at least 2 lines of prior therapy that included lenalidomide and a proteasome inhibitor.
Patients in this study received intravenous daratumumab (16 mg/kg) every week during the first 2 treatment cycles, then every 2 weeks for the next 4 cycles, and then monthly until progressive disease, unacceptable toxicity, withdrawal by patient or physician decision, or death. Coprimary endpoints were the median percent changes at 4 months compared with baseline for C-terminal cross-linking telopeptide of type 1 collagen (CTX) and for tartrate-resistant acid phosphatase 5b (TRACP-5b). CTX and TRACP-5b are markers of bone metabolism, and a variety of other markers of bone metabolism were also measured.
The study enrolled 57 patients, of whom 33 were evaluable in primary analysis after completing 4 months of therapy. Among patients included in the primary analysis, the overall response rate, including a partial response or better, was 63.6%. The primary analysis showed a median percent decrease between baseline and 4 months for CTX of 3.9%, and the median percent decrease in this time frame for TRACP-5b was 2.6%.
CTX levels were decreased by 20% or more in 39.4% of patients, and they were decreased by 30% in 33.3% of patients. TRACP-5b levels were decreased by 20% or more in 30.3% of patients and decreased by 30% in 18.2% of patients. Decreases in CTX or TRACP-5b levels, compared with baseline, were not considered statistically significant.
Some markers of bone formation were evaluated as secondary end points, with assessments of percent change between baseline and 4 months of therapy. For patients who had a partial response or better on daratumumab, the median increases in these markers were 25.3% for bone-specific alkaline phosphatase, 146.0% for osteocalcin, and 15.7% for procollagen type-I N-pro-peptide.
Safety analyses included all 57 enrolled patients. Serious adverse events that were considered to be related to daratumumab included grade 3-to-5 lower respiratory tract infections in 4 patients, grade 4 bronchospasm in 1 patient, and grade 3 febrile neutropenia in 1 patient.
“In conclusion, daratumumab showed a positive effect on bone metabolism in patients with relapsed/refractory MM primarily by reducing osteoblast inhibition and inducing bone formation,” the study investigators concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Terpos E, Ntanasis-Stathopoulos I, Kastritis E, et al. Daratumumab improves bone turnover in relapsed/refractory multiple myeloma; phase 2 study “REBUILD”. Cancers (Basel). 2022;14(11):2768. doi:10.3390/cancers14112768