Daratumumab Improves Bone Turnover in Relapsed/Refractory Multiple Myeloma; Phase 2 Study “REBUILD”
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Patient Selection
2.3. Study Endpoints
2.4. Evaluation of Bone Remodeling
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Impact of Daratumumab on Bone Metabolism
3.3. Efficacy and Survival
3.4. Safety
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Patient Disposition |
---|---|
Male sex, n (%) | 26 (45.6%) |
Karnofsky Performance Status, median (range) | 90 (70–100) |
Caucasian race, n (%) | 57 (100%) |
Age at enrolment, median (range), years | 73 (52–87) |
Age at diagnosis, median (range), years | 68 (44–83) |
Time from diagnosis to enrolment, median (Q1–Q3), years | 4.6 (2.9–7.7) |
Number of prior lines of therapy, median (range) | 3 (2–9) |
Prior ASCT, n (%) | 7 (12.3%) |
Refractory to the last line of therapy, n (%) | 41 (71.9%) |
Refractory to PI, n (%) | 37 (64.9%) |
Refractory to IMiD, n (%) | 47 (82.5%) |
Refractory to both PI and IMiD, n (%) | 36 (63.2%) |
No Lytic Bone Lesions, n (%) | 12 (21.1%) |
1–3 Lytic Bone Lesions, n (%) | 6 (10.5%) |
4–10 Lytic Bone Lesions, n (%) | 9 (15.8%) |
More than 10 Lytic Bone Lesions, n (%) | 30 (52.6%) |
ISS stage I, n (%) | 13 (22.8%) |
ISS stage II, n (%) | 24 (42.1%) |
ISS stage III, n (%) | 20 (35.1%) |
IgG Myeloma, n (%) | 29 (50.9%) |
IgA Myeloma, n (%) | 9 (15.8%) |
Kappa Light Chain Myeloma, n (%) | 8 (14.0%) |
Lamda Light Chain Myeloma, n (%) | 8 (14.0%) |
IgD Myeloma, n (%) | 1 (1.8%) |
Biclonal Myeloma, n (%) | 1 (1.8%) |
CTX (ng/mL), median (Q1, Q3) | 1.0 (0.4, 2.0) |
TRACP-5B (U/L), median (Q1, Q3) | 1.9 (1.1, 2.8) |
RANKL (pmol/L), median (Q1, Q3) | 0.1 (0.0, 0.2) |
bALP (μg/L), median (Q1, Q3) | 8.5 (6.6, 11.2) |
OC (ng/mL), median (Q1, Q3) | 2.7 (1.2, 6.3) |
PINP (pg/mL), median (Q1, Q3) | 521.0 (307.1, 1071.2) |
SOST (pmol/L), median (Q1, Q3) | 34.2 (21.0, 64.3) |
Dkk1 (pmol/L), median (Q1, Q3) | 58.1 (36.0, 100.6) |
CCL3 (ng/mL), median (Q1, Q3) | 35.4 (19.2, 57.5) |
Baseline | 2 Months | 4 Months | 6 Months | 8 Months | 10 Months | 12 Months | |
---|---|---|---|---|---|---|---|
bALP (μg/L) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | 2.1 (−0.7, 5.1) | 1.4 (−0.8, 3.6) | 1.7 (−1.8, 4.3) | 1.8 (−1.5, 5.2) | 2.0 (−0.5, 6.3) | 2.0 (−0.2, 4.8) | |
p-value for absolute change a | 0.005 | 0.045 | 0.129 | 0.129 | 0.055 | 0.215 | |
Osteocalcin (ng/mL) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | 2.0 (−1.2, 6.7) | 1.5 (−1.3, 6.7) | 1.1 (−3.2, 6.3) | 4.2 (1.2, 8.7) | 3.1 (−0.1, 7.5) | 4.4 (0.3, 9.7) | |
p-value for absolute change a | 0.023 | 0.061 | 0.039 | 0.001 | 0.014 | 0.008 | |
PINP (pg/mL) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | 35.2 (−167.3, 198.1) | 34.4 (−155.5, 225.8) | 82.7 (−98.8, 266.0) | 375.7 (36.0, 1785.0) | 149.5 (−103.8, 1880.4) | 376.5 (−80.7, 1539.3) | |
p-value for absolute change a | 0.686 | 0.348 | 0.810 | 0.010 | 0.074 | 0.085 | |
CTX (ng/mL) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | −0.0 (−0.2, 0.3) | 0.0 (−0.2, 0.3) | 0.1 (−0.0, 0.5) | 0.0 (−0.3, 0.7) | −0.1 (−0.6, 0.2) | −0.1 (−1.1, 0.0) | |
p-value for absolute change a | 0.728 | 0.695 | 0.990 | 0.522 | 0.179 | 0.060 | |
TRACP-5B (U/L) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | −0.2 (−0.7, 0.7) | −0.1 (−0.5, 0.7) | −0.1 (−0.9, 0.5) | 0.2 (−0.5, 1.0) | 0.3 (−0.6, 0.9) | 0.1 (−0.4, 0.6) | |
p-value for absolute change a | 0.753 | 0.273 | 0.720 | 0.277 | 0.780 | 0.969 | |
RANKL (pmol/L) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | 0.0 (−0.0, 0.1) | 0.0 (−0.0, 0.1) | 0.0 (−0.0, 0.1) | 0.0 (−0.0, 0.2) | 0.0 (0.0, 0.1) | 0.1 (0.0, 0.2) | |
p-value for absolute change a | 0.089 | 0.149 | 0.268 | 0.111 | 0.201 | 0.028 | |
RANKL/OPG ratio | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | 0.0 (−0.0, 0.0) | 0.0 (−0.0, 0.0) | 0.0 (−0.0, 0.0) | 0.0 (−0.0, 0.0) | 0.0 (−0.0, 0.0) | 0.0 (−0.0, 0.0) | |
p-value for absolute change a | 0.112 | 0.269 | 0.275 | 0.327 | 0.204 | 0.085 | |
SOST (pmol/L) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | −1.2 (−12.8, 6.0) | 2.8 (−13.9, 16.5) | −6.3 (−26.5, 8.0) | −4.1 (−42.1, 1.5) | 0.5 (−40.4, 19.5) | −4.0 (−33.4, 52.0) | |
p-value for absolute change a | 0.971 | 0.363 | 0.878 | 0.836 | 0.877 | 0.589 | |
DKK1 (pmol/L) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | −7.9 (−21.2, −1.5) | −8.7 (−29.2, −2.1) | −11.9 (−24.4, −2.4) | −13.7 (−25.7, −6.5) | −16.2 (−36.8, −9.7) | −17.0 (−33.6, −11.1) | |
p-value for absolute change a | 0.079 | 0.191 | 0.042 | 0.049 | 0.006 | 0.002 | |
CCL3 (ng/mL) | |||||||
n | 56 | 43 | 33 | 24 | 18 | 14 | 14 |
Median absolute change from baseline (Q1, Q3) | −2.4 (−6.0, 9.3) | −3.6 (−13.7, 1.7) | −5.7 (−28.2, 0.8) | −7.8 (−32.7, 5.3) | −10.4 (−25.9, 3.0) | −8.3 (−24.8, −0.7) | |
p-value for absolute change a | 0.366 | 0.068 | 0.021 | 0.007 | 0.008 | 0.006 |
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Terpos, E.; Ntanasis-Stathopoulos, I.; Kastritis, E.; Hatjiharissi, E.; Katodritou, E.; Eleutherakis-Papaiakovou, E.; Verrou, E.; Gavriatopoulou, M.; Leonidakis, A.; Manousou, K.; et al. Daratumumab Improves Bone Turnover in Relapsed/Refractory Multiple Myeloma; Phase 2 Study “REBUILD”. Cancers 2022, 14, 2768. https://doi.org/10.3390/cancers14112768
Terpos E, Ntanasis-Stathopoulos I, Kastritis E, Hatjiharissi E, Katodritou E, Eleutherakis-Papaiakovou E, Verrou E, Gavriatopoulou M, Leonidakis A, Manousou K, et al. Daratumumab Improves Bone Turnover in Relapsed/Refractory Multiple Myeloma; Phase 2 Study “REBUILD”. Cancers. 2022; 14(11):2768. https://doi.org/10.3390/cancers14112768
Chicago/Turabian StyleTerpos, Evangelos, Ioannis Ntanasis-Stathopoulos, Efstathios Kastritis, Evdoxia Hatjiharissi, Eirini Katodritou, Evangelos Eleutherakis-Papaiakovou, Evgenia Verrou, Maria Gavriatopoulou, Alexandros Leonidakis, Kyriaki Manousou, and et al. 2022. "Daratumumab Improves Bone Turnover in Relapsed/Refractory Multiple Myeloma; Phase 2 Study “REBUILD”" Cancers 14, no. 11: 2768. https://doi.org/10.3390/cancers14112768