Patient characteristics
A total of 394 patients with NDMM under 66 years old were enrolled, CD56 expression was detected in 265 (67.3%) patients and 175 (44.4%) patients received ASCT after induction therapy containing novel agents with 12 months. There were 119/265 (44.9%) and 56/129 (43.4%) received ASCT in CD56 positive and negative patients, respectively. Table 1 summarized the characteristics of 394 patients. The male-to-female ratio was 1.28 (221/173) and the median age was 55 (range 24–65) years old. The most common monoclonal protein was IgG type (49.2%) and 185 (47.0%) were at ISS stage III. All patients received induction therapy combining novel agents, 190 (48.2%) patients received bortezomib-based regimens, 41 (10.4%) combining immunomodulatory drugs (IMiDs), 163 (41.4%) combining bortezomib and IMiDs. After induction therapy, 175 (44.4%) patients received ASCT. As shown in Table 1, there were statistically significant differences between CD56 positive and negative patients in MM subtype, corrected serum calcium level (CsCa), lactate dehydrogenase (LDH), t(14; 16) and t(4; 14).
Table 1
Baseline clinical and biological characteristics of MM patients
| | all patients | CD56 positive | CD56 negative | |
Characteristics | n = 394 | n = 265 | n = 129 | |
| | n (%) | n (%) | n (%) | p value |
Sex |
| Male | 221(56.1) | 143(54.0) | 78(60.5) | 0.22 |
| Female | 173(43.9) | 122(46.0) | 51(39.5) |
MM subtype |
| IgG | 194(49.2) | 143(54.0) | 51(39.5) | 0.00 |
| IgA | 76(19.3) | 58(21.9) | 18(14.0) |
| IgD | 21(5.3) | 4(1.5) | 17(13.2) |
| Light chain only | 89(22.6) | 54(20.4) | 35(27.1) |
| Non-secretory | 14(3.6) | 6(2.3) | 8(6.2) |
ISS stage |
| I | 78(19.8) | 48(18.1) | 30(23.3) | 0.17 |
| II | 131(33.2) | 96(36.2) | 35(27.1) |
| III | 185(47.0) | 121(45.7) | 64(49.6) |
Hemoglobin |
| < 100 g/L | 244(61.9) | 168(63.4) | 76(58.9) | 0.39 |
| ≥ 100 g/L | 150(38.1) | 97(36.6) | 53(41.1) |
Serum creatinine |
| ≤ 2mg/dL | 321(81.5) | 219(82.6) | 102(79.1) | 0.39 |
| > 2mg/dL | 73(18.5) | 46(17.4) | 27(20.9) |
Corrected serum calcium |
| ≤ 2.75 mmol/L | 343(87.1) | 223(84.2) | 120(93.0) | 0.01 |
| > 2.75 mmol/L | 51(12.9) | 42(15.8) | 9(7.0) |
Lactate dehydrogenase |
| ≤ 250 U/L | 336(85.3) | 233(87.9) | 103(79.8) | 0.03 |
| > 250 U/L | 58(14.7) | 32(12.1) | 26(20.2) |
Cytogenetic abnormalities by FISH |
del(17p13) |
| abnormality | 38(9.6) | 27(10.2) | 11(8.5) | 0.60 |
| non-abnormality | 356(90.4) | 238(89.8) | 118(91.5) |
t(14; 16) |
| abnormality | 15(3.8) | 2(0.8) | 13(10.1) | 0.00 |
| non-abnormality | 379(96.2) | 263(99.2) | 116(89.9) |
t(4; 14) |
| abnormality | 69(17.5) | 66(24.9) | 3(2.3) | 0.00 |
| non-abnormality | 325(82.5) | 199(75.1) | 126(97.7) |
Induction regimes |
| Bortezomib based | 190(48.2) | 128(48.3) | 62(48.1) | 0.44 |
| IMiD based | 41(10.4) | 31(11.7) | 10(7.8) |
| Bortezomib and IMiD based | 163(41.4) | 106(40.0) | 57(44.2) |
ASCT |
| Yes | 175(44.4) | 119(44.9) | 56(43.4) | 0.78 |
| No | 219(55.6) | 146(55.1) | 73(56.6) |
Abbreviations: IMiD: immunomodulatory; ASCT: autologous stem cell transplant |
Multivariate Analysis For Survival
Univariate analysis found seven factors associated with OS and they were hemoglobin (HGB) < 100 g/L, LDH > 250 U/L, serum creatinine (SCr) > 2mg/dL, CsCa > 2.75mmol/L, del(17p13), t(14; 16), ISS III stage and ASCT. Multivariate analysis was performed for CD56, t(4; 14) and these eight covariates. It was showed that ASCT was a favorable factor for OS (HR = 0.43, 95%CI: 0.30–0.63, p < 0.001) and PFS (HR = 0.51, 95%CI: 0.38–0.68, p < 0.001) of patients with NDMM (Table 2). Among CD56 positive patients, univariate analyses showed that ASCT was a favorable factor for OS (HR = 0.36, 95%CI: 0.22–0.58, p < 0.001) and PFS (HR = 0.53, 95%CI: 0.37–0.74, p < 0.001); the favorable effect of ASCT on OS (HR = 0.30, 0.18–0.50, p < 0.001) and PFS (HR = 0.51, 0.36–0.72, p < 0.001) was confirmed in multivariate analyses (Table 2). Among CD56 negative patients, univariate analyses showed that ASCT was a favorable factor for PFS (HR = 0.54, 95%CI: 0.33–0.90, p = 0.02), but had no statistic impact on OS (p = 0.75); and multivariate analyses showed that ASCT had no effect on PFS (p = 0.08) and OS (p = 0.78) (Table 2).
Table 2
Cox analysis (univariate and multivariate) of ASCT
| all | | CD56 positive | | CD56 negative |
| P value HR (95% CI) | | P value HR (95% CI) | | P value HR (95% CI) |
Univariate | | | | | | | | |
OS | 0.00 | 0.47(0.32–0.68) | | 0.00 | 0.36(0.22–0.58) | | 0.75 | |
PFS | 0.00 | 0.53(0.40–0.70) | | 0.00 | 0.53(0.37–0.74) | | 0.02 | 0.54(0.33–0.90) |
Multivariate | | | | | | | | |
OS | 0.00 | 0.43(0.30–0.63) | | 0.00 | 0.30(0.18–0.50) | | 0.78 | |
PFS | 0.00 | 0.51(0.38–0.68) | | 0.00 | 0.51(0.36–0.72) | | 0.08 | |
Abbreviations: HR: hazard ratio; 95% CI: 95%confidence interval; ASCT: autologous stem cell transplant |
Matched Pairs Of Patients
Among CD56 positive patients, ASCT and non-ASCT patients were matched for ISS stage, HGB, SCr, CsCa, LDH, del(17p13), t(14; 16) and t(4; 14). A total of 216 patients were identified by propensity score matching technique, with 108 patients in each group. It was showed that there was no significantly difference in matched groups of ASCT and non-ASCT patients with respect to these characteristics (Table 3). Among CD56 negative patients, ASCT and non-ASCT patients were matched for above similar factors and 80 patients, 40 in each group, were identified. These two matched groups also had no difference in these factors (Table 3).
Table 3
Baseline clinical and biological characteristics of matched patients
Characteristics | CD56 positive | | CD56 negative |
ASCT | non-ASCT | | ASCT | non-ASCT |
n = 108 | n = 108 | | n = 40 | n = 40 |
n (%) | n (%) | | n (%) | n (%) |
ISS stage |
| I | 22(20.4) | 16(14.8) | | 9(22.5) | 8(20.0) |
| II | 41(38.0) | 50(46.3) | | 15(37.5) | 16(40.0) |
| III | 45(41.7) | 42(38.9) | | 16(40.0) | 16(40.0) |
Hemoglobin |
| < 100 g/L | 63(58.3) | 69(63.9) | | 24(60.0) | 24 (60.0) |
| ≥ 100 g/L | 45(41.7) | 39(36.1) | | 16(40.0) | 16 (40.0) |
Serum creatinine |
| ≤ 2mg/dL | 96(88.9) | 95(88.0) | | 34(85.0) | 36 (90.0) |
| > 2mg/dL | 12(11.1) | 13(12.0) | | 6(15.0) | 4 (10.0) |
Corrected serum calcium |
| ≤ 2.75 mmol/L | 93(86.1) | 89(82.4) | | 37(92.5) | 37 (92.5) |
| > 2.75 mmol/L | 15(13.9) | 19(17.6) | | 3(7.5) | 3 (7.5) |
Lactate dehydrogenase |
| ≤ 250 U/L | 97(89.8) | 93(86.1) | | 33(82.5) | 33 (82.5) |
| > 250 U/L | 11(10.2) | 15(13.9) | | 7(17.5) | 7 (17.5) |
Cytogenetic abnormalities by FISH |
del(17p13) |
| abnormality | 12(11.1) | 12(11.1) | | 3(7.5) | 2 (5.0) |
| non-abnormality | 96(88.9) | 96(88.9) | | 37(92.5) | 38 (95.0) |
t(14; 16) |
| abnormality | 0(0.0) | 0(0.0) | | 7(17.5) | 4 (10.0) |
| non-abnormality | 108(100.0) | 108(100.0) | | 33(82.5) | 36 (90.0) |
t(4; 14) |
| abnormality | 29(26.9) | 30(27.8) | | 0(0.0) | 0(0.0) |
| non-abnormality | 79(73.1) | 78(72.2) | | 40(100.0) | 40(100.0) |
Response Analysis
All patients were monitored for best response after ASCT and consolidation therapy. Among the 216 matched patients with CD56 expression, 200 (92.6%) patients achieved at least PR. Seventy-four patients (34.3%) achieved sCR, 28 (13.0%) CR, 61 (28.2%) VGPR, and 37 (17.1%) PR. Patients received ASCT had the higher sCR rate (46.3%) than those without ASCT (22.2%) in the matched groups (p < 0.001, Table 4). Among the 80 matched patients without CD56 expression, 77 (96.3%) patients achieved at least PR. Thirty-two patients (40.0%) achieved sCR, 10 (12.5%) CR, 20 (25.0%) VGPR, and 15 (18.8%) PR. Patients received ASCT also had the higher sCR rate (57.5%) than those without ASCT (22.5%) in the matched groups (p = 0.004, Table 4).
Table 4
Best response rate of matched patients
Response | CD56 positive | | CD56 negative |
ASCT | non-ASCT | | ASCT | non-ASCT |
n = 108 | n = 108 | | n = 40 | n = 40 |
n (%) | n (%) | | n (%) | n (%) |
sCR | 50(46.3) | 24(22.2) | | 23(57.5) | 9(22.5) |
CR | 18(16.7) | 10(9.3) | | 5(12.5) | 5(12.5) |
VGPR | 31(28.7) | 30(27.8) | | 10(25.0) | 10(25.0) |
PR | 7(6.5) | 30(27.8) | | 2(5.0) | 13(32.5) |
SD | 2(1.9) | 12(11.1) | | 0(0.0) | 2(5.0) |
PD | 0(0.0) | 2(1.9) | | 0(0.0) | 1(2.5) |
Abbreviations: sCR, stringent complete response; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease; PD, progressive disease. |
Survival Analysis
The median follow-up time for all patients was 30.0 (range 1.3-114.7) months. It was showed that ASCT could improve OS and PFS of patients (Fig. 1B and 2B). Among CD56 positive patients, the median OS were 87.6 (95% CI, 66.5-108.7) months and 54.1 (95% CI, 41.3–66.9) for patients with and without ASCT, respectively (p < 0.001, Fig. 1C); the median PFS were 40.1 (95% CI, 33.7–46.5) months and 25.8 (95% CI, 17.2–34.4) for patients with and without ASCT, respectively (p < 0.001, Fig. 2C). After matching, CD56 positive patients who received ASCT also had longer OS (87.6 vs.56.1 months, p < 0.001) and PFS (40.4 vs.27.6 months, p = 0.003) than those CD56 positive patients who had no ASCT (Fig. 1D and 2D). Among CD56 negative patients, the median OS were 56.2 (95% CI, 38.5–73.9) months and 53.9 (95% CI, 37.0-70.8) for patients with and without ASCT respectively (p = 0.748, Fig. 1C); the median PFS estimated were 35.5 (95% CI, 26.1–44.9) months and 22.0 (95% CI, 17.7–26.3) for patients with and without ASCT respectively (p = 0.016, Fig. 2C). After matching, CD56 negative patients received ASCT also had similar OS (49.2 vs.48.7 months, p = 0.569) and PFS (35.4 vs.22.9 months, p = 0.082) with those CD56 negative patients who had no ASCT (Fig. 1D and 2D).