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Early disease progression in EMZL
Validation set
Table 1 shows the main characteristics of the patients in the validation cohort, which comprised 287 MALT lym- phoma patients who received front-line systemic treat- ment (chemotherapy, immunotherapy or both). The median age of this set of patients was 63 years (range: 23 to 92 years). Most of these patients were female (60%).
Estimated hazard curves showed a peak risk of progres- sion at approximately 24 months after diagnosis (Figure 1B). After a median follow-up of 5.7 years, 64 patients (22%) had early POD. Fifty-four patients had a follow-up shorter than 2 years and nine died without prior disease progression within 2 years of starting treatment (Figure 2, right panel). Hence, the reference cohort comprised 160 patients, among whom relapses were later observed in 51 (33%). The early POD rates were similar in the groups of patients receiving different initial therapy (chemotherapy alone, rituximab alone or rituximab combined with differ- ent chemotherapeutic or immunomodulatory agents). Similar to the testing cohort, the early POD group was enriched in cases with transformation to aggressive histol- ogy (6 of 64 vs. 3 of 160 patients in the reference group, P=0.018) and early POD was most frequent in patients with elevated LDH (P<0.001), high-risk MALT-IPI scores
(P=0.001) and high-risk IPI scores (P=0.001) (Table 2). In addition, in the validation cohort, early POD was associ- ated with advanced disease stage (P=0.004) (Table 2).
As in the IELSG-19 study cohort, the patients in the val- idation set who experienced early POD after systemic therapy had an increased risk of death (HR=2.15; 95% CI: 1.19-3.90; log-rank P=0.009). In the early-POD group, the 5-year OS rate was 70% (95% CI: 54-81%), and the 10- year OS rate was 48% (95% CI: 28-66%). In comparison, the 5-year OS rate in the reference group was 88% (95% CI: 80-93%), and the 10-year OS rate was 71% (95% CI: 58-81%) (Figure 3B).
Table 3. Multivariate analysis for overall survival in the test set (step- wise Cox model, 383 patients).
AB
Figure 1. Risk of disease progression. (A, B) Estimated hazard of progression for patients in the test set, formed of a cohort of individuals from the International Extranodal Lymphoma Study Group-19 (IELSG-19) study (A) and for the patients included in the validation set (B).
Early POD 1.90
Age 1.13
MALT-IPI high risk 2.71
1.03-3.49
1.08-1.18
1.43-5.13
HR 95% CI
P-value 0.039
<0.001
0.002
HR: hazard ratio; 95% CI: 95% confidence interval; POD: progression of disease; MALT- IPI: Mucosa-Associated Lymphoid Tissue lymphoma International Prognostic Index.
Figure 2. Patients’ distribution.
The selection and distribution of patients according to timing of dis- ease progression in the test and validation sets. POD: progression of disease.
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