Page 166 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 6b
Table 2. Multivariable analysis of prognostic factors for FFS, PFS, and OS.
FFS
Factor HR
RR-CHOP-14 1.25 arm
Age ≥ 66 years 1.57
Age-adjusted IPI 1.09 scorea
Female sex 0.80
WHO 1.02 performance scoreb
LDH > ULN 1.51 B symptoms 1.12 Bulky disease 1.05 BM involvement 1.21
95% CI
0.98 to 1.61
1.21 to 2.03 0.81 to 1.46
0.63 to 1.04 0.82 to 1.28
1.00 to 2.30 0.86 to 1.46 0.79 to 1.38 0.84 to 1.75
PFS P HR .08 1.20
.001 1.58 .57 1.12
.09 0.85 .84 1.04
.051 1.46 .42 1.13 .75 0.93 .30 1.19
95% CI
0.93 to 1.54
1.21 to 2.04 0.84 to 1.51
0.66 to 1.09 0.83 to 1.30
0.96 to 2.23 0.87 to 1.49 0.70 to 1.24 0.82 to 1.72
OS P HR .16 1.25
.001 1.78 .44 1.17
.20 0.80 .76 1.12
.08 1.49 .36 1.08 .63 0.85 .36 0.98
95% CI
0.95 to 1.65
1.33 to 2.36 0.85 to 1.61
0.61 to 1.05 0.88 to 1.44
0.94 to 2.37 0.80 to 1.44 0.62 to 1.15 0.65 to 1.49
P
.10
< .001 .35
.11 .35
.09 .62 .29 .93
Abbreviations: BM, bone marrow; FFS, failure-free survival; HR, hazard ratio; IPI, International Prognostic Index; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; RR- CHOP, rituximab on days 1 and 8 of first 4 cycles and day 1 of remaining cycles plus cyclophosphamide, doxorubicin, vincristine, and prednisone (arm B); ULN, upper limit of normal.
a Analyzed as low v low-intermediate v high-intermediate v high. b Analyzed as WHO 0 v 1 v 2.
predictive values for 2-year PFS were 53% (95% CI, 42% to 64%) and 89% (95% CI, 85% to 91%) for EOT PET scans, respectively.
Rituximab Pharmacokinetics
Rituximab trough serum levels increased after each subsequent treatment cycle during the first 4 cycles and reached a plateau at cycles 5 to 8 in both treatment arms. Rituximab trough serum levels were systematically higher in the RR- CHOP-14–treated patients than in R-CHOP–treated patients (Appendix Figure A3, online only).
Adverse Events
We analyzed safety for all patients who received at least 1 administration of study treatment. The proportion of patients with at least 1 adverse or serious adverse event did not differ between the R-CHOP-14 and RR-CHOP-14 arms. The most common grade 3 and 4 adverse events were cytopenias and infections (Table 3). During the first 4 cycles, patients between ages 66 and 80 years experienced significantly more toxicity in the RR-CHOP-14 arm, especially neutropenia and infections (Table 4).
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