Baseline characteristics
The baseline characteristics of patients at the time of MM diagnosis were presented in Table 1. A total of 209 patients were included in the final analysis and were divided into four groups (G1, G2, G3, and G4) based on the time from achieving VGPR/CR to MM progression: G1 (TTP ≤ 6 months, 13 cases), G2 (TTP ≤ 12 months, 57 cases), G3 (TTP ≤ 24 months, 97 cases), and G4 (TTP > 24 months, 112 cases). The median age of patients in G1-4 groups was 68, 64, 63, and 62 years, respectively, showing a gradual decrease in age. Among the four groups, no significant differences were observed in the categorical distribution of gender, body mass index (BMI), comprehensive complication index (CCI), M protein type, hemoglobin (HGB) level, platelet (PLT) count, neutrophil (NEU) count, lymphocyte (LYM) count, blood calcium level, β2-microglobulin, serum creatinine (Scr) level, lactate dehydrogenase (LDH), albumin (ALB) level, bone disease, cytogenetic risk, treatment after progression, and treatment response before progression. However, the G1 group had the highest proportion of patients with high Eastern Cooperative Oncology Group (ECOG) scores compared to the other three groups. Patients in the G2 group were more likely to have high-risk features, including ISS stage and C-reactive protein (CRP). The G3 group showed the highest proportion of plasma cells in the bone marrow. Of the 209 patients who received treatment after the first MM progression, 31 (14.83%) patients continued conventional chemotherapy, 125 (59.81%) patients chose PIs or/and IMiDs-based chemotherapy, and ASCT was performed in the remaining 53 (25.36%) patients. There was no significant difference in the proportion of the three treatments among the four groups.
Table 1
Correlations between MM progression and clinical features in MM patients who have achieved VGPR/CR.
Patient features | G1 (TTP ≤ 6 months, N = 13) n (%) | G2 (TTP ≤ 12 months, N = 57) n (%) | G3 (TTP ≤ 24 months, N = 97) n (%) | G4 (TTP > 24 months, N = 112) n (%) | χ2 | P |
Age (median, years) | 68 | 64 | 63 | 62 | 16.305 | 0.001 |
< 68 | 3 (23.08) | 33 (57.89) | 56 (57.73) | 83 (74.11) | | |
≥ 68 | 10 (76.92) | 24 (42.11) | 41 (42.27) | 29 (25.89) | | |
Gender | | | | | 1.48 | 0.687 |
Male | 9(69.23) | 35(61.4) | 53 (54.64) | 63 (56.25) | | |
Female | 4(30.77) | 22(38.60) | 44 (45.36) | 49 (43.75) | | |
BMI | | | | | 2.894 | 0.408 |
< 22.77 | 6(46.15) | 29(51.79) | 48 (50) | 45 (40.18) | | |
≥ 22.77 | 7(53.85) | 27(48.21) | 48 (50) | 67(59.82) | | |
ECOG | | | | | 15.362 | 0.001 |
≤ 1 | 4(30.77) | 30(52.63) | 55 (57.29) | 83 (74.11) | | |
≥ 2 | 9(69.23) | 27(47.37) | 41 (42.71) | 29 (25.89) | | |
CCI | | | | | 6.685 | 0.073 |
≤ 1 | 8(61.54) | 45(80.36) | 79 (82.29) | 99 (88.39) | | |
≥ 2 | 5(38.46) | 11(19.64) | 17(17.71) | 13 (11.61) | | |
ISS stage | | | | 10.071 | 0.018 |
I-II | 7(53.85) | 24(42.11) | 42 (43.30) | 70(62.5) | | |
Ⅲ | 6(46.15) | 33(57.89) | 55 (56.70) | 42(37.5) | | |
M protein type | | | | 5.213 | 0.516 |
IgG | 7(53.85) | 22(38.6) | 39 (40.21) | 61 (54.46) | | |
IgA | 4(31.33) | 21(36.84) | 33(34.02) | 30(26.79) | | |
Light chain | 1(18.08) | 11(19.30) | 18(18.56) | 21(18.75) | | |
BMPC% | | | | | 9.345 | 0.023 |
<35.25 | 8(72.73) | 32(57.14) | 41(42.71) | 67(62.04) | | |
≥35.25 | 3(27.27) | 24(42.86) | 55(57.29) | 41(37.96) | | |
HGB (g/L) | | | | 0.912 | 0.832 |
< 81.5 | 4(30.77) | 22(38.60) | 39(40.21) | 39(34.82) | | |
≥81.5 | 9(69.23) | 35(61.40) | 58(59.79) | 73(65.18) | | |
PLT (x 10^9/L) | | | | 0.221 | 0.974 |
< 167 | 8(61.54) | 34(59.65) | 55(56.70) | 64(57.14) | | |
≥ 167 | 5(38.46) | 23(40.35) | 42(43.30) | 48(42.86) | | |
NEU (x 10^9/L) | | | | 1.955 | 0.588 |
< 1.785 | 3(23.08) | 9(15.79) | 11(11.34) | 16(14.29) | | |
≥ 1.785 | 10(76.92) | 48(84.21) | 86(88.66) | 96(85.71) | | |
LYM (x 10^9/L) | | | | 3.009 | 0.39 |
< 1.43 | 6(46.15) | 28(49.12) | 46(47.42) | 42(37.5) | | |
≥ 1.43 | 7(53.85) | 29(50.88) | 51(52.58) | 70(62.5) | | |
Ca2+ (mmol/L) | | | | 2.013 | 0.57 |
< 2.505 | 10(30.77) | 34(59.65) | 55(56.70) | 68(60.71) | | |
≥2.505 | 3(69.23) | 23(40.35) | 42(43.30) | 44(39.29) | | |
β2-MG (mg/L) | | | | 0.9 | 0.825 |
< 4.78 | 5(38.46) | 28(49.12) | 48(50) | 51(45.54) | | |
≥ 4.78 | 8(61.54) | 29(50.88) | 48(50) | 61(54.46) | | |
Scr (mmol/L) | | | | 4.011 | 0.258 |
< 137.5 | 6(46.15) | 41(71.93) | 71(73.20) | 81(72.32) | | |
≥ 137.5 | 7(53.85) | 16(28.07) | 26(26.80) | 31(27.68) | | |
LDH (U/L) | | | | 4.338 | 0.226 |
< 151.5 | 2(15.38) | 17(29.82) | 40(41.24) | 39(34.82) | | |
≥ 151.5 | 11(84.62) | 40(70.18) | 57(58.76) | 73(65.18) | | |
ALB (g/L) | | | | 1.596 | 0.675 |
< 27.45 | 1(7.69) | 13(22.81) | 23(23.71) | 27(24.11) | | |
≥ 27.45 | 12(92.31) | 44(77.19) | 74(76.29) | 85(75.89) | | |
CRP (mg/L) | | | | 24.32 | < 0.001 |
< 5.845 | 6(46.15) | 19(33.33) | 41(42.27) | 77(68.75) | | |
≥ 5.845 | 7(53.85) | 38(66.67) | 56(57.73) | 35(31.25) | | |
Bone disease | | | | 1.438 | 0.709 |
Yes | 11(84.62) | 46(80.70) | 77(79.38) | 83(74.11) | | |
No | 2(15.38) | 11(19.30) | 20(20.62) | 29(25.89) | | |
Cytogenetic abnormalities | | | | |
Standard risk | 7(53.85) | 31(54.39) | 56(57.73) | 80(71.43) | 6.923 | 0.071 |
High risk | 6(46.15) | 26(45.61) | 41(42.27) | 32(28.57) | | |
P53 deficiency/mutation | 4(30.77) | 10(17.54) | 13(13.40) | 8(7.14) | | |
1q21 gain/amplification | 3(23.08) | 19(33.33) | 33(34.02) | 32(28.57) | | |
IGH rearrangement | 8(61.54) | 26(45.61) | 45(46.39) | 45(40.18) | | |
13q- | 5(38.46) | 12(21.05) | 21(21.65) | 31(27.68) | | |
Treatment after progression | | | | | |
Conventional chemotherapy | 3(23.07) | 13(22.81) | 16(16.49) | 15(13.39) | 6.661 | 0.345 |
PIs or/and IMiDs based chemotherapy | 8(61.54) | 28(49.12) | 52(53.61) | 73(65.18) | | |
ASCT | 2(15.38) | 16(28.07) | 29(29.90) | 24(21.43) | | |
Treatment response | | | 1.485 | 0.686 |
CR | 6(46.15) | 24(42.11) | 38(39.18) | 53(50.56) | | |
VGPR | 7(53.85) | 33(57.89) | 59(60.82) | 59(49.44) | | |
ALB: albumin, ASCT: autologous hematopoietic stem cell transplantation, BMI: body mass index, BMPC: bone marrow plasmacyte, β2-MG: β2-microglobulin, Ca2+: calcium, CCI: comprehensive complication index, CI: confidence interval, CR: complete remission, CRP: C-reactive protein, ECOG: eastern cooperative oncology group, G1-4: group 1–4, HGB: hemoglobin, IMiDs: immunomodulatory drugs, ISS: international staging system, LDH: lactate dehydrogenase, LYM: lymphocyte, NEU: neutrophil, PIs: proteasome inhibitors, PLT: platelet, Scr: serum creatinine, TTP: time to progression, VGPR: very good partial remission. |
Survival
A total of 209 MM patients who achieved VGPR/CR after first-line therapy were followed up for a median duration of 69.06 months (95% CI: 60.57–77.57 months). During the follow-up, 186 (89%) cases experienced MM progression, with 103 (55.38%) cases progressing after VGPR and 83 (44.62%) cases progressing after CR. There were 66 deaths, of which 5 cases were due to causes unrelated to MM. As depicted in Fig. 1A and B, the median PFS and OS for patients in the G1 group were 9.27 and 33.63 months, respectively, compared to 13.17 and 61.73 months in the G2 group (P = 0.038 and P = 0.084, respectively). Patients in the G2 group had a shorter median PFS and OS compared to those in the G3 group (13.17 vs 16.10 months, P < 0.001; 61.73 vs 96.10 months, P = 0.02, Fig. 1A, B), as well as a shorter median PFS and OS for patients in the G3 vs G4 group (16.10 vs 47.7 months, P < 0.001; 96.10 vs 121.73 months, P < 0.001; Fig. 1A, B).
Furthermore, to analyze the patients with 6 months < TTP ≤ 24 months, we specifically subdivided them into two additional groups: G5 (6 months < TTP ≤ 12 months, 44 cases) and G6 (12 months < TTP ≤ 24 months, 40 cases). Comparing the G1 group with the G5 group, the median PFS and OS for patients in the G1 group were 9.27 and 33.63 months, respectively, while for patients in the G5 group, they were 13.53 months and 79.60 months (P = 0.017 and P = 0.022, respectively, Fig. 2A, B). Furthermore, compared to the G5 group, patients in the G6 group showed longer median PFS and OS (22.33 vs 13.53 months, P < 0.001; 100.43 vs 79.60 months, P < 0.001, Fig. 2A, B). In addition, comparing the G4 group with the G6 group, the median PFS and OS for patients in the G4 group were 47.7 months and 121.73 months, respectively, while for patients in the G6 group, they were 22.33 months and 100.43 months (P < 0.001 and P = 0.683, respectively, Fig. 2A, B).
Taking into consideration the impact of post-progression treatment on survival, we categorized patients into three groups based on their post-progression treatment: conventional chemotherapy group, PIs or/and IMiDs based chemotherapy group, and ASCT group. For patients who experienced progression within 12 months after VGPR/CR, those in the ASCT group had a significant median OS advantage compared to those in the conventional chemotherapy group or the PIs or/and IMiDs based chemotherapy group (100.43 vs 30.37 months, P = 0.002; 100.43 vs 47.20 months, P = 0.022, Fig. 3A). Additionally, the PIs or/and IMiDs based chemotherapy group demonstrated a longer median OS compared to the conventional chemotherapy group (47.2 vs 30.37 months, P = 0.036, Fig. 3A). Similarly, for patients who progressed within 24 months after VGPR/CR, the ASCT group exhibited a superior median OS of 101 months compared to 54.8 months in the conventional chemotherapy group or 96.1 months in the PIs or/and IMiDs based chemotherapy group (P < 0.001 and P = 0.004, Fig. 3B). Furthermore, PIs or/and IMiDs-based chemotherapy also improved the median OS relative to conventional chemotherapy (96.1 vs 54.8 months, P = 0.002, Fig. 3B).
Univariable and multivariable analysis for OS and PFS
A univariable analysis demonstrated that TTP after VGPR or CR strongly predicted OS and PFS in patients with MM. Additionally, factors such as age, ECOG performance status, CCI, ISS stage, and cytogenetic abnormalities were also found to be associated with PFS and OS. Serum creatinine level and treatment after disease progression were significant predictors for OS, while lymphocyte count and CRP level showed predictive significance for PFS in univariable analysis. Variables that were statistically significant in the univariable analysis were included in a multivariable analysis. Based on TTP, three different Cox proportional hazards models were constructed to evaluate their impact on OS and PFS. The multivariable analysis in all three models confirmed the positive effects of standard-risk cytogenetics, ASCT, and longer TTP durations (> 6 months, > 12 months, and > 24 months) on OS. In Cox proportional hazards model 1, TTP (≤ 6 months vs > 6 months), lymphocyte count, CRP level, and cytogenetic abnormalities were independent predictive factors for PFS. In Cox model 2, TTP (≤ 12 months vs > 12 months), age, ECOG status, CCI, and lymphocyte count were all independently associated with PFS. Lastly, in Cox model 3, CRP level was the only variable showing independent predictive significance for PFS. (Table 2, 3)
Table 2
Univariate and multivariate analyses of prognostic factors for OS in MM patients who achieved VGPR/CR.
| Univariate analysis | | Model1 | | Model2 | | Model3 |
Variables | | Multivariate analysis | | Multivariate analysis | | Multivariate analysis |
| HR (95% CI) | P value | | HR (95% CI) | P value | | HR (95% CI) | P value | | HR (95% CI) | P value |
Age (< 68 vs ≥ 68) | 2.322(1.391–3.877) | 0.001 | | 0.668(0.306–1.461) | 0.313 | | 0.85(0.401-1.8) | 0.671 | | 0.704(0.332–1.492) | 0.359 |
Gender (Male vs Female) | 1.153(0.716–1.857) | 0.558 | | | | | | | | | |
BMI (< 22.77 vs ≥ 22.77) | 0.827(0.512–1.335) | 0.437 | | | | | | | | | |
ECOG (≤ 1 vs ≥ 2) | 2.523(1.538–4.138) | < 0.001 | 1.833(0.959–3.503) | 0.067 | | 1.47(0.772-2.800) | 0.241 | | 1.728(0.934–3.198) | 0.082 |
CCI (≤ 1 vs ≥ 2) | 3.479(1.982–6.107) | < 0.001 | 1.710(0.765–3.824) | 0.191 | | 1.767(0.825–3.785) | 0.143 | | 1.874(0.87–4.033) | 0.108 |
ISS stage (I-II vs Ⅲ) | 1.889(1.167–3.056) | 0.01 | | 1.494(0.906–2.465) | 0.116 | | 1.374(0.827–2.285) | 0.22 | | 1.300(0.777–2.174) | 0.318 |
BMPC% (< 35.25 vs ≥ 35.25) | 1.589(0.913–2.768) | 0.102 | | | | | | | | | |
HGB (g/L, < 81.5 vs ≥ 81.5) | 1.354(0.803–2.282) | 0.256 | | | | | | | | | |
PLT (x 10^9/L, < 167 vs ≥ 167) | 0.781(0.475–1.282) | 0.328 | | | | | | | | | |
NEU (x 10^9/L, < 1.785 vs ≥ 1.785) | 1.841(0.834–4.066) | 0.131 | | | | | | | | | |
LYM (x 10^9/L, < 1.43 vs ≥ 1.43) | 1.306(0.797–2.139) | 0.289 | | | | | | | | | |
Ca2+ (mmol/L, < 2.505 vs ≥ 2.505) | 1.555(0.966–2.503) | 0.069 | | | | | | | | | |
β2-MG (mg/L, < 4.78 vs ≥ 4.78) | 1.067(0.662–1.72) | 0.789 | | | | | | | | | |
Scr (mmol/L, < 137.5 vs ≥ 137.5) | 1.806(1.107–2.948) | 0.018 | | 1.393(0.822–2.358) | 0.185 | | 1.569(0.933–2.638) | 0.09 | | 1.388(0.804–2.395) | 0.239 |
LDH (U/L, < 151.5 vs ≥ 151.5) | 1.076(0.659–1.757) | 0.771 | | | | | | | | | |
ALB (g/L, < 27.45 vs ≥ 27.45) | 1.206(0.680–2.141) | 0.521 | | | | | | | | | |
CRP (mg/L, < 5.845 vs ≥ 5.845) | 1.406(0.870–2.272) | 0.165 | | | | | | | | | |
Bone disease (Yes vs No) | 1.112(0.64–1.931) | 0.706 | | | | | | | | | |
Cytogenetic abnormalities (Standard risk vs High risk) | 3.078(1.893–5.004) | < 0.001 | 2.507(1.491–4.217) | 0.001 | 2.021(1.189–3.436) | 0.009 | | 2.277(1.347–3.85) | 0.002 |
Treatment after progression | | | | | | | | | | | |
Conventional chemotherapy vs PIs or/and IMiDs based chemotherapy | 0.377(0.197–0.724) | 0.003 | | | | | | | | | |
Conventional chemotherapy vs ASCT | 0.349(0.216–0.565) | < 0.001 | | | | | | | | |
PIs or/and IMiDs based chemotherapy vs ASCT | 0.379(0.198–0.727) | 0.003 | | | | | | | | | |
Conventional chemotherapy or PI or/and IMiD based chemotherapy vs ASCT | 0.328(0.175–0.615) | 0.001 | 0.321(0.165–0.623) | 0.001 | | 0.204(0.103–0.405) | < 0.001 | | 0.275(0.141–0.534) | < 0.001 |
Treatment response (CR vs VGPR) | 1.193(0.733–1.941) | 0.477 | | | | | | | | | |
TTP after VGPR/CR | | | | | | | | | | |
≤ 6 months vs > 6 months | 0.129(0.056–0.294) | < 0.001 | 0.278(0.11–0.702) | 0.007 | | | | | | |
≤ 12 months vs > 12 months | 0.209(0.121–0.361) | < 0.001 | | | | 0.177(0.093–0.339) | < 0.001 | | | |
≤ 24 months vs > 24 months | 0.404(0.246–0.665) | < 0.001 | | | | | | | | 0.49(0.279–0.859) | 0.013 |
ALB: albumin, ASCT: autologous hematopoietic stem cell transplantation, BMI: body mass index, BMPC: bone marrow plasmacyte, β2-MG: β2-microglobulin, Ca2+: calcium, CCI: comprehensive complication index, CI: confidence interval, CR: complete remission, CRP: C-reactive protein, ECOG: eastern cooperative oncology group, HGB: hemoglobin, IMiDs: immunomodulatory drugs, ISS: international staging system, LDH: lactate dehydrogenase, LYM: lymphocyte, NEU: neutrophil, PIs: proteasome inhibitors, PLT: platelet, Scr: serum creatinine, TTP: time to progression, VGPR: very good partial remission. |
Table 3
Univariate and multivariate analyses of prognostic factors for PFS in MM patients who achieved VGPR/CR.
| Univariate analysis | | Model1 | | Model2 | | Model3 |
Variables | | Multivariate analysis | | Multivariate analysis | | Multivariate analysis |
| HR (95% CI) | P value | | HR (95% CI) | P value | | HR (95% CI) | P value | | HR (95% CI) | P value |
Age (< 68 vs ≥ 68) | 1.464(1.07–2.003) | 0.017 | | 1.451(0.958–2.196) | 0.079 | | 1.626(1.086–2.434) | 0.018 | | 1.411(0.955–2.086) | 0.084 |
Gender (Male vs Female) | 0.977(0.73–1.307) | 0.874 | | | | | | | | | |
BMI (< 22.77 vs ≥ 22.77) | 0.831(0.62–1.114) | 0.216 | | | | | | | | | |
ECOG (≤ 1 vs ≥ 2) | 1.573(1.166–2.121) | 0.003 | | 1.076(0.735–1.575) | 0.706 | | 0.798(0.541–1.179) | 0.258 | | 1.026(0.72–1.462) | 0.888 |
CCI (≤ 1 vs ≥ 2) | 1.619(1.069–2.452) | 0.023 | | 1.064(0.666-1.700) | 0.795 | | 1.244(0.79–1.959) | 0.346 | | 1.23(0.772–1.96) | 0.385 |
ISS stage (I-II vs Ⅲ) | 1.433(1.067–1.926) | 0.017 | | 1.236(0.903–1.691) | 0.186 | | 1.125(0.819–1.545) | 0.466 | | 1.126(0.825–1.537) | 0.453 |
BMPC% (< 35.25 vs ≥ 35.25) | 1.284(0.906–1.818) | 0.16 | | | | | | | | | |
HGB (g/L, < 81.5 vs ≥ 81.5) | 0.902(0.667–1.219) | 0.502 | | | | | | | | | |
PLT (x 10^9/L, < 167 vs ≥ 167) | 1.101(0.82–1.479) | 0.521 | | | | | | | | | |
NEU (x 10^9/L, < 1.785 vs ≥ 1.785) | 1.179(0.765–1.818) | 0.456 | | | | | | | | | |
LYM (x 10^9/L, < 1.43 vs ≥ 1.43) | 0.626(0.467–0.84) | 0.002 | | 0.641(0.47–0.875) | 0.005 | | 0.729(0.532–0.997) | 0.048 | | 0.737(0.541–1.004) | 0.053 |
Ca2+ (mmol/L, < 2.505 vs ≥ 2.505) | 1.249(0.930–1.679) | 0.14 | | | | | | | | | |
β2-MG (mg/L, < 4.78 vs ≥ 4.78) | 0.987(0.739–1.318) | 0.928 | | | | | | | | | |
Scr (mmol/L, < 137.5 vs ≥ 137.5) | 1.121(0.813–1.547) | 0.486 | | | | | | | | | |
LDH (U/L, < 151.5 vs ≥ 151.5) | 1.18(0.872–1.596) | 0.284 | | | | | | | | | |
ALB (g/L, < 27.45 vs ≥ 27.45) | 1.108(0.785–1.563) | 0.559 | | | | | | | | | |
CRP (mg/L, < 5.845 vs ≥ 5.845) | 1.938(1.435–2.619) | < 0.001 | | 1.829(1.327–2.521) | < 0.001 | | 1.314(0.928–1.862) | 0.124 | | 1.451(1.055–1.996) | 0.022 |
Bone disease (Yes vs No) | 1.122(0.797–1.581) | 0.51 | | | | | | | | | |
Cytogenetic abnormalities (Standard risk vs High risk) | 1.442(1.066–1.949) | 0.017 | | 1.398(1.015–1.924) | 0.04 | | 1.301(0.947–1.788) | 0.105 | | 1.069(0.78–1.465) | 0.678 |
Treatment after progression | | | | | | | | | | | |
Conventional chemotherapy vs PIs or/and IMiDs based chemotherapy | 0.784(0.505–1.217) | 0.278 | | | | | | | | | |
Conventional chemotherapy vs ASCT | 0.817(0.493–1.351) | 0.43 | | | | | | | | | |
PIs or/and IMiDs based chemotherapy vs ASCT | 0.886(0.628–1.251) | 0.493 | | | | | | | | | |
Conventional chemotherapy or PIs or/and IMiDs based chemotherapy vs ASCT | 0.856(0.612–1.199) | 0.366 | | | | | | | | | |
Treatment response (CR vs VGPR) | 1.142(0.852–1.53) | 0.374 | | | | | | | | | |
TTP after VGPR/CR | | | | | | | | | |
≤ 6 months vs > 6 months | 0.07(0.038–0.129) | < 0.001 | | 0.112(0.057–0.223) | < 0.001 | | | | | | |
≤ 12 months vs > 12 months | 0.022(0.013–0.04) | < 0.001 | | | | | 0.024(0.013–0.045) | < 0.001 | | | |
≤ 24 months vs > 24 months | 0.002(0.00-0.014) | < 0.001 | | | | | | | | 0.00(0.00-520.1) | 0.693 |
ALB: albumin, ASCT: autologous hematopoietic stem cell transplantation, BMI: body mass index, BMPC: bone marrow plasmacyte, β2-MG: β2-microglobulin, Ca2+: calcium, CCI: comprehensive complication index, CI: confidence interval, CR: complete remission, CRP: C-reactive protein, ECOG: eastern cooperative oncology group, HGB: hemoglobin, IMiDs: immunomodulatory drugs, ISS: international staging system, LDH: lactate dehydrogenase, LYM: lymphocyte, NEU: neutrophil, PIs: proteasome inhibitors, PLT: platelet, Scr: serum creatinine, TTP: time to progression, VGPR: very good partial remission. |
Factors associated with myeloma progression
Through the utilization of logistic regression models, a univariable analysis revealed that a poor ECOG performance status and high CRP level were associated with an increased risk of developing MM progression within 12 months after VGPR/CR. These findings were further confirmed as independent predictors for MM progression through multivariable analysis (Table 4). Furthermore, the univariable analysis indicated that ECOG performance status, ISS stage, CRP level, and cytogenetic abnormalities significantly influenced MM progression within 24 months after VGPR/CR. Specifically, poor ECOG status, ISS stage III, and high CRP level independently increased the risk of MM progression according to the multivariable analysis (Table 5).
Table 4
Univariate and multivariate analyses of risk factors for MM progression within 12 months after VGPR/CR.
Variables | Univariate analysis | | Multivariate analysis |
OR (95% CI) | P value | | OR (95% CI) | P value |
Age (< 68 vs ≥ 68) | 1.338(0.712–2.514) | 0.365 | | | |
Gender (Male vs Female) | 0.779(0.422–1.44) | 0.426 | | | |
BMI (< 22.77 vs ≥ 22.77) | 0.69(0.377–1.261) | 0.227 | | | |
ECOG (≤ 1 vs ≥ 2) | 2.124(1.147–3.933) | 0.017 | | 2.383(1.229–5.647) | 0.01 |
CCI (≤ 1 vs ≥ 2) | 1.711(0.767–3.817) | 0.189 | | | |
ISS stage (I-II vs Ⅲ) | 1.747(0.951–3.207) | 0.072 | | | |
BMPC% (< 35.25 vs ≥ 35.25) | 1.316(0.661–2.622) | 0.435 | | | |
HGB (g/L, < 81.5 vs ≥ 81.5) | 0.839(0.451–1.561) | 0.579 | | | |
PLT (x 10^9/L, < 167 vs ≥ 167) | 0.799(0.434–1.471) | 0.472 | | | |
NEU (x 10^9/L, < 1.785 vs ≥ 1.785) | 0.762(0.327–1.776) | 0.529 | | | |
LYM (x 10^9/L, < 1.43 vs ≥ 1.43) | 0.637(0.348–1.168) | 0.145 | | | |
Ca2+ (mmol/L, < 2.505 vs ≥ 2.505) | 0.924(0.501–1.703) | 0.8 | | | |
β2-MG (mg/L, < 4.78 vs ≥ 4.78) | 0.896(0.491–1.637) | 0.721 | | | |
Scr (mmol/L, < 137.5 vs ≥ 137.5) | 1.005(0.515–1.961) | 0.989 | | | |
LDH (U/L, < 151.5 vs ≥ 151.5) | 0.657(0.344–1.254) | 0.202 | | | |
ALB (g/L, < 27.45 vs ≥ 27.45) | 1.331(0.645–2.744) | 0.439 | | | |
CRP (mg/L, < 5.845 vs ≥ 5.845) | 3.6(1.908–6.791) | < 0.001 | | 3.914(2.025–7.563) | < 0.001 |
Bone disease (Yes vs No) | 1.439(0.684–3.026) | 0.338 | | | |
Cytogenetic abnormalities (Standard risk vs High risk) | 1.771(0.959–3.27) | 0.068 | | | |
Treatment response (CR vs VGPR) | 0.982(0.534–1.805) | 0.954 | | | |
ALB: albumin, BMI: body mass index, BMPC: bone marrow plasmacyte, β2-MG: β2-microglobulin, Ca2+: calcium, CCI: comprehensive complication index, CI: confidence interval, CR: complete remission, CRP: C-reactive protein, ECOG: eastern cooperative oncology group, HGB: hemoglobin, ISS: international staging system, LDH: lactate dehydrogenase, LYM: lymphocyte, NEU: neutrophil, OR: odds ratio, PLT: platelet, Scr: serum creatinine, VGPR: very good partial remission. |
Table 5
Univariate and multivariate analyses of risk factors for MM progression within 24 months after VGPR/CR.
Variables | Univariate analysis | | Multivariate analysis |
OR (95% CI) | P value | | OR (95% CI) | P value |
Age (< 68 vs ≥ 68) | 1.278(0.727–2.246) | 0.393 | | | |
Gender (Male vs Female) | 1.091(0.641–1.858) | 0.748 | | | |
BMI (< 22.77 vs ≥ 22.77) | 0.676(0.397–1.152) | 0.15 | | | |
ECOG (≤ 1 vs ≥ 2) | 2.029(1.16–3.548) | 0.013 | | 2.147(1.146–4.023) | 0.017 |
CCI (≤ 1 vs ≥ 2) | 1.621(0.765–3.437) | 0.208 | | | |
ISS stage (I-II vs Ⅲ) | 1.914(1.121–3.266) | 0.017 | | 2.368(1.299–4.317) | 0.005 |
BMPC% (< 35.25 vs ≥ 35.25) | 1.245(0.665–2.329) | 0.493 | | | |
HGB (g/L, < 81.5 vs ≥ 81.5) | 0.96(0.554–1.666) | 0.96 | | | |
PLT (x 10^9/L, < 167 vs ≥ 167) | 0.922(0.542–1.568) | 0.763 | | | |
NEU (x 10^9/L, < 1.785 vs ≥ 1.785) | 1.363(0.616–3.017) | 0.445 | | | |
LYM (x 10^9/L, < 1.43 vs ≥ 1.43) | 0.622(0.363–1.065) | 0.083 | | | |
Ca2+ (mmol/L, < 2.505 vs ≥ 2.505) | 1.116(0.654–1.905) | 0.687 | | | |
β2-MG (mg/L, < 4.78 vs ≥ 4.78) | 0.802(0.472–1.362) | 0.413 | | | |
Scr (mmol/L, < 137.5 vs ≥ 137.5) | 0.901(0.499–1.624) | 0.728 | | | |
LDH (U/L, < 151.5 vs ≥ 151.5) | 0.721(0.418–1.244) | 0.24 | | | |
ALB (g/L, < 27.45 vs ≥ 27.45) | 1.118(0.605–2.063) | 0.722 | | | |
CRP (mg/L, < 5.845 vs ≥ 5.845) | 2.797(1.62–4.829) | < 0.001 | | 3.399(1.853–6.234) | < 0.001 |
Bone disease (Yes vs No) | 1.393(0.742–2.612) | 0.302 | | | |
Cytogenetic abnormalities (Standard risk vs High risk) | 1.809(1.041–3.142) | 0.035 | | 1.73(0.934–3.206) | 0.082 |
Treatment response (CR vs VGPR) | 1.208(0.706–2.066) | 0.491 | | | |
ALB: albumin, BMI: body mass index, BMPC: bone marrow plasmacyte, β2-MG: β2-microglobulin, Ca2+: calcium, CCI: comprehensive complication index, CI: confidence interval, CR: complete remission, CRP: C-reactive protein, ECOG: eastern cooperative oncology group, HGB: hemoglobin, ISS: international staging system, LDH: lactate dehydrogenase, LYM: lymphocyte, NEU: neutrophil, OR: odds ratio, PLT: platelet, Scr: serum creatinine, VGPR: very good partial remission. |