Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient’ Selection
2.2. Imaging Methods
2.3. Bone-Marrow Assessment
2.4. Response Assessment and Survival Intervals
2.5. Statistics
3. Results
3.1. Clinical Characteristics of Patients
3.2. Treatment of PS and EMD Subgroups of Patients after NDMM Diagnosis
3.3. High-Risk Features in PS Subgroup of Patients
3.4. High-Risk Features in EMD Subgroup of Patients
3.5. Heterogeneity in PS and EMD Subgroups of Patients
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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Univariable Analysis | ||||
---|---|---|---|---|
Overall Survival (OS) | Progression-Free Survival (PFS) | |||
HR (95% CI) 1 | p | HR (95% CI) 1 | p | |
ISS | ||||
Stage I | – | – | – | – |
Stage II | 2.01 (1.46–2.75) | <0.001 | 1.87 (1.41–2.48) | <0.001 |
Stage III | 2.24 (1.60–3.13) | <0.001 | 2.30 (1.71–3.10) | <0.001 |
R-ISS | ||||
Stage I | – | – | – | – |
Stage II | 3.00 (1.40–6.42) | 0.005 | 1.73 (1.04–2.88) | 0.035 |
Stage III | 4.78 (2.20–10.38) | <0.001 | 2.13 (1.24–3.66) | 0.006 |
Serum M-protein level (g/dL) | ||||
≤2 | – | – | – | – |
>2 | 1.20 (0.92–1.55) | 0.180 | 1.25 (0.98–1.58) | 0.068 |
BM PCs % | ||||
<5% | – | – | – | – |
≥5% | 3.12 (1.95–5.00) | <0.001 | 2.38 (1.67–3.39) | <0.001 |
Plasmacytoma count | ||||
1–2 plasmacytomas | – | – | – | – |
≥3 plasmacytomas | 1.75 (1.20–2.55) | 0.003 | 1.39 (0.97–1.99) | 0.073 |
Tumor burden | ||||
BM PCs < 5% and 1 and more plasmacytoma | – | – | – | – |
BM PCs ≥ 5% and 1–2 plasmacytomas | 3.01 (1.82–4.97) | <0.001 | 2.47 (1.68–3.62) | <0.001 |
BM PC ≥ 5% and 3 and more plasmacytomas | 4.86 (2.69–8.80) | <0.001 | 3.17 (1.93–5.20) | <0.001 |
Clonal PCs from all BM PC (%) | ||||
<95% | – | – | – | – |
≥95% | 2.01 (1.20–3.36) | 0.008 | 1.59 (1.08–2.32) | 0.018 |
Osteolytic lesions | ||||
negative | – | – | – | – |
1 lesion | 1.10 (0.15–8.21) | 0.925 | 0.52 (0.12–2.21) | 0.375 |
2 lesions | 1.33 (0.18–9.98) | 0.779 | 0.90 (0.21–3.80) | 0.882 |
≥3 lesions | 1.36 (0.19–9.73) | 0.758 | 0.89 (0.22–3.57) | 0.866 |
Accelerated osteoporosis | 0.54 (0.03–8.62) | 0.662 | 0.57 (0.08–4.02) | 0.569 |
LDH (IU/L) | ||||
>300 | 2.52 (1.74–3.67) | <0.001 | 2.50 (1.76–3.56) | <0.001 |
IGH disruption | ||||
Positive | 1.18 (0.81–1.71) | 0.385 | 1.16 (0.84–1.61) | 0.378 |
t(11;14) | ||||
Positive | 1.39 (0.79–2.45) | 0.258 | 1.03 (0.59–1.81) | 0.913 |
t(4;14) | ||||
Positive | 2.37 (1.41–3.98) | 0.001 | 1.87 (1.14–3.05) | 0.013 |
Del(13)(q14)/monosomy 13 | ||||
Positive | 1.44 (0.99–2.10) | 0.059 | 1.12 (0.80–1.55) | 0.516 |
Gain(1q21) | ||||
Positive | 1.32 (0.90–1.93) | 0.157 | 1.67 (1.20–2.33) | 0.003 |
Del(17p13) | ||||
Positive | 2.17 (1.32–3.56) | 0.002 | 1.74 (1.09–2.78) | 0.020 |
Hyperdiploidy | ||||
Positive | 0.64 (0.41–0.99) | 0.045 | 0.79 (0.54–1.16) | 0.227 |
Univariable Analysis | ||||
---|---|---|---|---|
Overall Survival (OS) | Progression-Free Survival (PFS) | |||
HR (95% CI) 1 | p | HR (95% CI) 1 | p | |
ISS | ||||
Stage I | – | – | – | – |
Stage II | 1.49 (0.87–2.56) | 0.151 | 1.48 (0.93–2.37) | 0.102 |
Stage III | 3.21 (1.94–5.31) | <0.001 | 2.49 (1.60–3.89) | <0.001 |
R-ISS | ||||
Stage I | – | – | – | – |
Stage II | 1.77 (0.63–4.93) | 0.276 | 2.07 (0.93–4.63) | 0.075 |
Stage III | 5.64 (2.08–15.26) | 0.001 | 5.03 (2.21–11.48) | <0.001 |
Serum M-protein level (g/dL) | ||||
>2 | 1.13 (0.75–1.71) | 0.565 | 1.34 (0.93–1.94) | 0.122 |
BM PCs % | ||||
<5% | – | – | – | – |
≥5% | 1.30 (0.76–2.20) | 0.338 | 1.56 (0.97–2.52) | 0.066 |
Plasmacytoma count | ||||
1–2 lesions | – | – | – | – |
≥3 lesions | 2.00 (1.21–3.30) | 0.007 | 1.88 (1.18–2.98) | 0.008 |
Clonal PCs from all BM PC (%) | ||||
≥95% | 1.36 (0.72–2.59) | 0.346 | 1.41 (0.83–2.39) | 0.210 |
Osteolytic lesions | ||||
Negative | – | – | – | – |
1 lesion | 0.33 (0.11–1.03) | 0.055 | 0.56 (0.16–2.04) | 0.382 |
2 lesions | 0.26 (0.07–0.90) | 0.033 | 0.45 (0.12–1.70) | 0.236 |
≥3 lesions | 0.49 (0.20–1.21) | 0.122 | 0.65 (0.20–2.06) | 0.461 |
Accelerated osteoporosis | 0.39 (0.09–1.62) | 0.194 | 0.52 (0.12–2.19) | 0.372 |
LDH (IU/L) | ||||
> 300 | 2.29 (1.20–4.38) | 0.012 | 1.88 (1.03–3.43) | 0.041 |
IGH disruption | ||||
Positive | 1.19 (0.67–2.12) | 0.557 | 1.14 (0.69–1.89) | 0.612 |
t(11;14) | ||||
Positive | 1.01 (0.31–3.33) | 0.988 | 0.57 (0.14–2.37) | 0.441 |
t(4;14) | ||||
Positive | 0.77 (0.33–1.78) | 0.542 | 1.55 (0.80–2.99) | 0.191 |
Del(13)(q14)/monosomy 13 | ||||
Positive | 1.06 (0.59–1.90) | 0.851 | 1.53 (0.94–2.49) | 0.087 |
Gain(1q21) | ||||
Positive | 1.86 (1.06–3.27) | 0.031 | 1.82 (1.11–2.99) | 0.019 |
Del(17p13) | ||||
Positive | 2.62 (1.21–5.67) | 0.014 | 2.96 (1.46–6.00) | 0.003 |
Hyperdiploidy | ||||
Positive | 1.06 (0.55–2.02) | 0.867 | 1.18 (0.65–2.15) | 0.593 |
Characteristics 1 | BM PCs < 5% and 1 or More Plasmacytomas (n = 91) | BM PCs ≥ 5% and 1–2 Plasmacytomas (n = 302) | BM PCs ≥ 5% and ≥3 Plasmacytomas (n = 58) | p-Value 2 |
---|---|---|---|---|
ISS | n = 91 | n = 298 | n = 58 | |
Stage I | 63 (69.2%) | 113 (37.9%) | 17 (29.3%) | <0.001 |
Stage II | 16 (17.6%) | 103 (34.6%) | 17 (29.3%) | |
Stage III | 12 (13.2%) | 82 (27.5%) | 24 (41.4%) | |
R-ISS | n = 18 | n = 120 | n = 38 | |
Stage I | 7 (38.9%) | 25 (20.8%) | 4 (10.5%) | 0.195 |
Stage II | 7 (38.9%) | 63 (52.5%) | 21 (55.3%) | |
Stage III | 4 (22.2%) | 32 (26.7%) | 13 (34.2%) | |
Serum M-protein level (g/dL) | n = 91 | n = 302 | n = 58 | |
≤2 | 66 (72.5%) | 145 (48.0%) | 26 (44.8%) | <0.001 |
>2 | 25 (27.5%) | 157 (52.0%) | 32 (55.2%) | |
Plasmacytoma count | n = 91 | n = 302 | n = 58 | |
1 plasmacytoma | 73 (80.2%) | 263 (87.1%) | - | <0.001 |
2 plasmacytomas | 12 (13.2%) | 39 (12.9%) | - | |
3 plasmacytomas | 1 (1.1%) | - | 16 (27.6%) | |
>3 plasmacytomas | 5 (5.5%) | - | 42 (72.4%) | |
Clonal PCs from all BM PC (%) | n = 57 | n = 159 | n = 25 | |
<95% | 38 (66.7%) | 37 (23.3%) | 1 (4.0%) | <0.001 |
≥95% | 19 (33.3%) | 122 (76.7%) | 24 (96.0%) | |
Osteolytic lesions | n = 91 | n = 302 | n = 58 | |
Negative | 0 (0.0%) | 2 (0.7%) | 0 (0.0%) | <0.001 |
1 lesion | 17 (18.7%) | 32 (10.6%) | 0 (0.0%) | |
2 lesions | 3 (3.3%) | 28 (9.3%) | 0 (0.0%) | |
≥3 lesions | 70 (76.9%) | 238 (78.8%) | 58 (100.0%) | |
Accelerated osteoporosis | 1 (1.1%) | 2 (0.7%) | 0 (0.0%) | |
LDH (IU/L) | n = 91 | n = 296 | n = 58 | |
≤300 | 84 (92.3%) | 271 (91.6%) | 53 (91.4%) | 1.000 |
>300 | 7 (7.7%) | 25 (8.4%) | 5 (8.6%) | |
IGH disruption | n = 24 | n = 183 | n = 37 | |
Negative | 22 (91.7%) | 106 (57.9%) | 18 (48.6%) | 0.001 |
Positive | 2 (8.3%) | 77 (42.1%) | 19 (51.4%) | |
t(11;14) | n = 23 | n = 156 | n = 32 | |
Negative | 22 (95.7%) | 135 (86.5%) | 25 (78.1%) | 0.195 |
Positive | 1 (4.3%) | 21 (13.5%) | 7 (21.9%) | |
t(4;14) | n = 25 | n = 161 | n = 34 | |
Negative | 25 (100.0%) | 145 (90.1%) | 29 (85.3%) | 0.119 |
Positive | 0 (0.0%) | 16 (9.9%) | 5 (14.7%) | |
Del(13)(q14)/monosomy 13 | n = 24 | n = 183 | n = 36 | |
Negative | 14 (58.3%) | 100 (54.6%) | 20 (55.6%) | 0.975 |
Positive | 10 (41.7%) | 83 (45.4%) | 16 (44.4%) | |
Gain(1q21) | n = 24 | n = 176 | n = 38 | |
Negative | 17 (70.8%) | 111 (63.1%) | 19 (50.0%) | 0.203 |
Positive | 7 (29.2%) | 65 (36.9%) | 19 (50.0%) | |
Del(17p13) | n = 24 | n = 165 | n = 35 | |
Negative | 24 (100.0%) | 146 (88.5%) | 30 (85.7%) | 0.141 |
Positive | 0 (0.0%) | 19 (11.5%) | 5 (14.3%) | |
Hyperdiploidy | n = 20 | n = 129 | n = 36 | |
Negative | 12 (60.0%) | 75 (58.1%) | 20 (55.6%) | 0.945 |
Positive | 8 (40.0%) | 54 (41.9%) | 16 (44.4%) |
Characteristics 1 | 1–2 EMD Plasmacytomas (n = 158) | ≥3 EMD Plasmacytomas (n = 36) | p-Value 2 |
---|---|---|---|
ISS | n = 156 | n = 36 | |
Stage I | 68 (43.6%) | 11 (30.6%) | 0.189 |
Stage II | 43 (27.6%) | 9 (25.0%) | |
Stage III | 45 (28.8%) | 16 (44.4%) | |
R-ISS | n = 65 | n = 21 | |
Stage I | 17 (26.2%) | 3 (14.3%) | 0.173 |
Stage II | 26 (40.0%) | 6 (28.6%) | |
Stage III | 22 (33.8%) | 12 (57.1%) | |
Serum M-protein level (g/dL) | n = 158 | n = 36 | |
≤ 2 | 81 (51.3%) | 18 (50.0%) | 1.000 |
> 2 | 77 (48.7%) | 18 (50.0%) | |
Clonal PCs from all BM PCs (%) | n = 95 | n = 15 | |
<95% | 37 (38.9%) | 6 (40.0%) | 1.000 |
≥95% | 58 (61.1%) | 9 (60.0%) | |
BM PCs % | n = 152 | n = 33 | |
<5% | 38 (25.0%) | 9 (27.3%) | 0.826 |
≥5% | 114 (75.0%) | 24 (72.7%) | |
Osteolytic lesions | n = 156 | n = 36 | |
Negative | 6 (3.8%) | 0 (0.0%) | 0.115 |
1 lesion | 18 (11.5%) | 2 (5.6%) | |
2 lesions | 15 (9.6%) | 0 (0.0%) | |
≥3 lesions | 110 (70.5%) | 32 (88.9%) | |
Accelerated osteoporosis | 7 (4.5%) | 2 (5.6%) | |
LDH (IU/L) | n = 158 | n = 36 | |
≤ 300 | 146 (92.4%) | 31 (86.1%) | 0.322 |
> 300 | 12 (7.6%) | 5 (13.9%) | |
IGH disruption | n = 88 | n = 17 | |
Negative | 58 (65.9%) | 9 (52.9%) | 0.409 |
Positive | 30 (34.1%) | 8 (47.1%) | |
t(11;14) | n = 72 | n = 14 | |
Negative | 67 (93.1%) | 12 (85.7%) | 0.319 |
Positive | 5 (6.9%) | 2 (14.3%) | |
t(4;14) | n = 86 | n = 17 | |
Negative | 76 (88.4%) | 16 (94.1%) | 0.686 |
Positive | 10 (11.6%) | 1 (5.9%) | |
Del(13)(q14)/monosomy 13 | n = 89 | n = 17 | |
Negative | 53 (59.6%) | 11 (64.7%) | 0.791 |
Positive | 36 (40.4%) | 6 (35.3%) | |
Gain(1q21) | n = 88 | n = 17 | |
Negative | 51 (58.0%) | 7 (41.2%) | 0.287 |
Positive | 37 (42.0%) | 10 (58.8%) | |
del(17p13) | n = 86 | n = 15 | |
Negative | 72 (83.7%) | 11 (73.3%) | 0.462 |
Positive | 14 (16.3%) | 4 (26.7%) | |
Hyperdiploidy | n = 61 | n = 14 | |
Negative | 30 (49.2%) | 5 (35.7%) | 0.393 |
Positive | 31 (50.8%) | 9 (64.3%) |
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Stork, M.; Sevcikova, S.; Jelinek, T.; Minarik, J.; Radocha, J.; Pika, T.; Pospisilova, L.; Spicka, I.; Straub, J.; Pavlicek, P.; et al. Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas. Biomedicines 2022, 10, 2535. https://doi.org/10.3390/biomedicines10102535
Stork M, Sevcikova S, Jelinek T, Minarik J, Radocha J, Pika T, Pospisilova L, Spicka I, Straub J, Pavlicek P, et al. Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas. Biomedicines. 2022; 10(10):2535. https://doi.org/10.3390/biomedicines10102535
Chicago/Turabian StyleStork, Martin, Sabina Sevcikova, Tomas Jelinek, Jiri Minarik, Jakub Radocha, Tomas Pika, Lenka Pospisilova, Ivan Spicka, Jan Straub, Petr Pavlicek, and et al. 2022. "Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas" Biomedicines 10, no. 10: 2535. https://doi.org/10.3390/biomedicines10102535