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A.S. Zayac et al.
59% versus 77% in patients with or without CNS disease, respectively (OR=0.45 [0.29-0.69], P<0.001; excluding untreated patients) as well as worse PFS (3-year estimate, 46% vs. 69%, respectively; HR=2.02 [1.52-2.67], P<0.001) (Figure 1C) and OS (49% vs. 74%, respectively; HR=2.18 [1.61-2.94], P<0.001) (Figure 1D). Patients with CNS involvement had a median PFS of 1.1 years [range, 0.5-4.2] and OS of 2.6 years [0.9 to not reached], whereas medians for those without CNS disease were not reached.
CNS involvement remained an independent risk factor for PFS (adjusted HR=1.53 [1.14-2.06], P=0.004) and OS (adjusted HR=1.62 [1.18-2.22], P=0.003) after adjustment for other characteristics independently associated with poor outcomes: age ≥40 years, ECOG PS 2-4, and LDH level >3xULN.16 We observed no difference in PFS based on whether the CNS involvement was parenchymal or lep- tomeningeal only (log-rank P=0.90), but patients with CNS disease who were diagnosed at age ≥60 years had worse
survival (Online Supplementary Figure S1A-D). As expected, the four patients with parenchymal CNS disease who received DA-EPOCH-R had particularly poor outcomes (3- year PFS 25% vs. 57% for those treated with CODOX- M/IVAC and 56% for those given hyperCVAD/MA) (Online Supplementary Figure S1E and F).
Inferior PFS with baseline CNS involvement was observed regardless of the first-line treatment regimen given (Pinteraction=0.85) (Figure 2A-C) or whether rituximab was used (Pinteraction=0.75). Similarly, complete response rates were lower with baseline CNS involvement across regimens (Pinteraction=0.95) (Figure 2D) and independent of rituximab use
=0.65). interaction
Central nervous system recurrence
BL recurred in 167 patients (26%), with 39 (6%) present- ing a CNS recurrence (21 with and 18 without CNS involvement at diagnosis) (Online Supplementary Figure S2A).
AB
CD
Figure 2. Prognostic significance of baseline central nervous system involvement among patients treated with specific first-line chemotherapy regimens. (A-C) Progression-free survival stratified by the presence of central nervous system (CNS) involvement at diagnosis, for patients treated with: (A) CODOX-M/IVAC (n=194); (B) hyper-CVAD/MA (n=195); and (C) DA-EPOCH-R (n=181). Shaded areas indicate 95% confidence interval bands; 3-year survival estimates and P-values from a log- rank test are listed; the summary P-value for interaction between baseline CNS involvement and chemotherapy regimen was 0.85. (D) Proportions of patients achiev- ing complete response (CR) to first-line therapy, stratified by specific regimen and baseline CNS involvement; the summary P-value for interaction between CNS involvement and chemotherapy regimen was 0.95.
(P
1936
haematologica | 2021; 106(7)