MPT, melphalan, prednisone, and thalidomide; Rd cont, lenalidomide plus low-dose dexamethasone until disease progression; Rd18, lenalidomide plus low-dose dexamethasone for 18 cycles; Rd pooled, Rd cont and Rd18 patients combined; TE, treatment emergent. Supplemental Table 4. Microbiology of TE Infections by Treatment Arm During the First 4 and 18 Months of Treatment in the FIRST Trial TE Infections, n 0-4 Months 0-18 Months Rd Pooled MPT Total Rd Pooled MPT Total Grade ≥ 3 Infections Bacterial Clostridia Enterococcal Escherichia Klebsiella Legionella Neisseria Pseudomonal Salmonella Staphylococcal Streptococcal 35 5 0 4 0 0 2 2 0 8 10 18 4 0 0 2 0 0 4 0 1 1 53 9 0 4 2 0 2 6 0 9 11 78 8 0 6 1 3 2 3 3 17 14 24 5 1 1 2 1 0 5 0 1 1 102 13 1 7 3 4 2 8 3 18 15
Neisseria Pseudomonal Staphylococcal Streptococcal 1 1 1 1 0 1 0 0 1 2 1 1 1 1 1 1 0 1 0 0 1 2 1 1 Fungal Pneumocystis 0 0 0 0 0 0 0 0 1 1 1 1 Infections—pathogen unspecified* 16 7 23 34 12 46 Viral Hepatitis Influenza 0 0 0 1 1 0 1 1 0 1 0 1 1 1 0 2 1 1 Total 21 9 30 40 15 55 MPT, melphalan, prednisone, and thalidomide; Rd cont, lenalidomide plus low-dose dexamethasone until disease progression; Rd18, lenalidomide plus low-dose dexamethasone for 18 cycles; TE, treatment emergent. * In total, 30 of these infections were reported as sepsis, bacteremia, viremia, and fungemia other; 13 as lower respiratory tract and lung infections; 2 as central nervous system and spinal infections; and 1 as other infections.
Supplemental Table 5. Stepwise Multivariate Time-Dependent Analysis for OS Variable Coefficient* Hazard Ratio P value Estimate SE TE grade ≥ 3 infection 2.205 0.244 9.07 < 2 × 10−16 Systolic blood pressure ≤ 108 mm Hg 0.550 0.165 1.73 8.60 × 10−4 History of bone, calcium, magnesium, and phosphorus metabolism disorders† = yes 0.281 0.158 1.32 7.64 × 10−2 Serum β2-microglobulin ≥ 8.38 mg/L 0.352 0.118 1.42 2.80 × 10−3 Renal insufficiency‡ = yes −0.289 −0.163 0.75 7.65 × 10−2 High-risk cytogenetics§ = yes 0.702 0.120 2.02 4.81 × 10−9 ECOG PS ≥ 2 0.332 0.101 1.39 9.71 × 10−4 Fitness category combined with ISS stage‖ = frail with ISS stage III −0.269 −0.127 0.76 3.33 × 10−2 Absolute lymphocytes ≤ 0.9 × 109/L 0.402 0.104 1.50 1.02 × 10−4 ISS stage ≥ 3 0.474 0.125 1.61 1.59 × 10−4 Red blood cells ≤ 3.1 × 1012/L 0.287 0.088 1.33 1.16 × 10−3 Global quality of life ≤ 50 0.284 0.092 1.33 2.05×10−3 α-1 globulin ≥ 5% 0.174 0.099 1.19 7.91 × 10−2
Supplemental Table 7. Baseline Patient Characteristics Associated With Increased or Decreased Risk of TE Grade ≥ 3 Infection in the First 4 Months Found with an Exploratory Univariate Analysis using the Q-Finder algorithm Variable Patients, n (%) Patients With TE Grade ≥ 3 Infections, % Odds Ratio (CI) P Value All patients (analysis set) 1 378 (100) 13.9 Fitness category combined with ISS stage* = frail with ISS stage III 308 (22.4) 22.7 2.31 (1.7-3.2) 8.25 × 10−7 ECOG PS ≥ 2† 280 (20.3) 22.5 2.20 (1.6-3.1) 5.97 × 10−6 Serum β2-microglobulin ≥ 5.94 mg/L† 478 (34.7) 24.1 3.43 (2.5-4.7) 6.66 × 10−15 Serum β2-microglobulin ≤ 2.89 mg/L† 207 (15.0) 3.4 0.19 (0.1-0.4) 7.79 × 10−8 M-protein urine ≥ 616.1 mg/24 h 376 (27.3) 20.7 2.06 (1.5-2.8) 8.33 × 10−6 Urea ≥ 23 mg/dL 452 (32.8) 21.0 2.30 (1.7-3.1) 1.24 × 10−7 Urea ≤ 19 mg/dL 731 (53.0) 9.8 0.48 (0.4-0.7) 3.26 × 10−6 α-1 globulin (corrected) ≥ 0.4 g/dL 624 (45.3) 18.9 2.18 (1.6-3.0) 6.10 × 10−7 Creatinine ≥ 1.2 mg/dL† 445 (32.3) 20.4 2.14 (1.6-2.9) 1.36 × 10−6 Lactate dehydrogenase ≥ 200 U/L† 242 (17.6) 24.0 2.38 (1.7-3.4) 1.79 × 10−6
Coefficient P Value Coefficient Estimate Estimate SE ECOG PS = 0 −0.427 0.210 .042 -0.403 ECOG PS ≥ 2 0.360 0.165 .029 0.457 Hemoglobin ≤ 11 g/dL 0.389 0.197 .048 0.366 LDH ≥ 200 U/L 0.330 0.169 .051 0.552 Sβ2M ≤ 3 mg/L −0.817 0.356 .022 -0.812 Sβ2M ≥ 6 mg/L 0.669 0.167 6 × 10−5 0.820 ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; Sβ2M, serum TE, treatment emergent.