Daratumumab Improves Bone Turnover in Relapsed/Refractory Multiple Myeloma; Phase 2 Study “REBUILD”

Abstract

Biomarkers of bone turnover in serum are suggestive of bone dynamics during treatment in multiple myeloma (MM). We evaluated the role of daratumumab on bone remodeling among patients with relapsed/refractory MM in the prospective, open-label, phase 2 study REBUILD. Daratumumab was administered according to the approved indication. A total of 33 out of 57 enrolled patients completed 4 months of treatment. The median percent change from baseline to 4 months in C-terminal cross-linking telopeptide of type 1 collagen (CTX) (primary endpoint) was 3.9%, with 13 (39.4%) and 11 (33.3%) patients showing at least 20% and 30% reduction in CTX levels, respectively. The median percent decrease from baseline to 4 months in tartrate resistant acid phosphatase 5b (TRACP-5b) levels (co-primary endpoint) was 2.6%, with 10 (30.3%) and 6 (18.2%) patients showing at least 20% and 30% reduction in TRACP-5b levels, respectively. However, the changes in these markers of bone catabolism were not statistically significant. Furthermore, the levels of osteocalcin, bone-specific alkaline phosphatase and procollagen type-I N-pro-peptide (bone formation markers) increased from baseline to 4 months (secondary endpoints) by 18.4%, 92.6% and 10.2%, respectively. Furthermore, the median levels of dickkopf-1 and C-C motif ligand-3 showed a significant decrease at 4 months by 17.5% and 16.0%, respectively. In conclusion, daratumumab improved bone turnover by inducing bone formation and reducing osteoblast inhibition.

Efficacy and safety of daratumumab with ixazomib and dexamethasone in lenalidomide‐exposed patients after one prior line of therapy: Final results of the phase 2 study DARIA

“…Biomarkers of bone metabolism were evaluated at baseline and every 3 months until disease progression or end of study treatment. The measurements were based on enzyme‐linked immunosorbent assays (ELISA), as described previously in detail 18 …”

“…The measurements were based on enzyme-linked immunosorbent assays (ELISA), as described previously in detail. 18…”

“…32,33 Patient adherence to selinexor may be challenging mainly due to gastrointestinal toxicity, fatigue, decreased appetite and weight loss. 34 Although some patients may derive benefit from monotherapy with daratumumab or isatuximab, the survival outcomes are often suboptimal 18,[35][36][37] ; therefore, triplets should be preferred in all patients. 1 In addition to the above, novel immunotherapies including chimeric antigen receptor (CAR) T-cells and bispecific antibodies have shown significant activity for patients with RRMM and they are currently under investigation in earlier lines of therapy.…”

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents

“…The REBUILD trial is a notable clinical study with daratumumab monotherapy to evaluate the role of daratumumab in bone remodeling among patients with RRMM [ 100 ]. Daratumumab monotherapy did not show statistically significant differences in serum levels of indicators of bone resorption, C-terminal cross-linking telopeptide of type 1 collagen and tartrate resistant acid phosphatase 5b (TRACP-5b), nor changes in the RANKL/OPG ratios over time.…”

Hotspots and trends in multiple myeloma bone diseases: A bibliometric visualization analysis

“…Terpos E from the National and Kapodistrian University of Athens, Greece, is the author with the most publications, reflecting that he is academically highly influential with outstanding contributions in the field. His recent study showed that daratumumab improved bone turnover in relapsed/refractory Multiple Myeloma by inducing bone formation and reducing osteoblast inhibition(Terpos et al, 2022). On the other hand, Terpos E has active partnerships with Anderson KC, Dimopoulos MA, Rajkumar SV, Kyle RA, Roodman GD, Palumbo A, Cavo M, Durie BGM and Raje N. At the same time, this research field has also formed core research teams represented by Terpos E, Anderson KC, Dimopoulos MA, Rajkumar SV, Dispenzieri A and Goldschmidt H. In addition, further analysis shows that the top 10 authors with highyield and high-centrality are all from Europe or the United States.…”