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N. Gagelmann et al.
80.3% (95%CI: 75.6-85.1; P=0.88). Patients with EM involvement showed no significant difference in both 3- year PFS and OS after tandem versus single transplantation: 56.2% (95%CI: 27.2-85.3) versus 48.3% (95%CI: 36.6-60.1; P=0.98), and 52.0% (95%CI: 20.0-84.0) versus 64.9% (95%CI: 54.2-75.7; P=0.39).
Role of other factors on survival and causes of death
All patients in CR before first ASCT showed a signifi- cantly better 3-year PFS of 59.8% (95%CI: 55.3-64.3) com- pared to 30.7% (95%CI: 28.2-33.2) in PR and 24.7% (95%CI: 17.6-31.8; P<0.001) in less than PR. There was also a significant difference in 3-year OS, with patients in CR showing 83.6% (95%CI: 80.2-87.0) compared to 78.8% (95%CI: 76.9-80.6) in patients with PR and 27.8% (95%CI: 20.8-34.9) in patients with less than PR (P<0.001).
Other factors associated with worse PFS in patients with EMD were: older age (P=0.04), transplantation before 2011 (P=0.01), higher disease stage according to ISS (P=0.01) and Salmon and Durie (P=0.02), and lower remission status at transplantation (P<0.001). Factors associated with worse OS in EMD patients were: transplantation before 2011 (P=0.02), higher disease stage according to ISS (P=0.002)
and Salmon and Durie (P=0.02), and lower remission status at transplantation (P<0.001).
Non-relapse mortality at three years occurred in 3.0% (95%CI: 2.0-4.0) of MM, 3.0% (95%CI: 2.0-5.0) of PS patients, and 7.0% (95%CI: 2.0-12.0) of EM patients (P=0.05). Main causes of death were relapse or progression (86.3%), infection (7.1%), secondary malignancy or post- transplant lymphoproliferative disorder (3.6%), organ damage or failure (1.8%), toxicity (0.4%), and unknown in 83 patients.
Multivariate analyses
A multivariable model was constructed to examine the effect of EMD on 3-year PFS and OS after adjusting for possible prognostic factors. All factors and covariates including corresponding references are listed in Table 3. To avoid linearly dependent covariates, we merged the dis- ease group and the new variable of the number of involved sites into a 5-level variable consisting of patients without EMD (MM group) and patients with EMD according to number of involved sites (PS1, PS2, EM1 and EM2). Cox proportional hazards regression considering independent factors for worse PFS yielded significant results for EM2
Table 2. Involved sites in extramedullary organ involvement (EM) group and survival after autologous stem cell transplantation (ASCT).
Site
Kidney
CNS
Lung / respiratory tract GI tract / liver
Pleura / heart
Spleen / ovaries / testes Skin
Lymph nodes
N. of patients (%)
38 (27.3)
14 (10.1) 9 (6.5) 8 (5.8) 7 (5.0) 7 (5.0) 32 (23.0)
24 (17.3)
N. of deaths
7
4
3
3
5
2
10
10
3-year PFS in % (95% CI)
59.5 (41.1 to 77.9)
47.9 (18.3 to 77.4)
44.4 (7.4 to 81.5)
22.5 (0 to 58.8)
NE
60.0 (17.1 to 100)
20.1 (3.4 to 36.7)
37.6 (16.4 to 58.7)
3-year OS in % (95% CI)
75.3 (59.0 to 91.7)
64.3 (35.5 to 93.1)
41.7 (0 to 85.1)
58.3 (22.0 to 94.7)
NE
60.0 (17.1 to 100)
53.3 (30.5 to 76.0)
48.2 (25.1 to 71.3)
PFS: progression-free survival; OS: overall survival; N.: number; CI: Confidence Interval; CNS: central nervous system; GI: gastrointestinal; NE: not estimable.
Figure 2. Progression-free survival (A) and overall survival (B) with numbers at risk of myeloma patients following up-front autologous stem cell transplantation according to number of involvements: 0, 1 and ≥ 2. N: number.
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