Gafter‐Gvili, Anat

Abstract Background: Marginal zone Lymphoma (MZL) is the third most abundant lymphoma and it is subclassified into 3 entities: splenic, nodal and extranodal mucosa associated lymphoid tissue (MALT). Positron emission tomography (PET) using 18F fluorodeoxyglucose (FDG) with computed tomography (CT) is increasingly used for staging and response assessment of FDG avid lymphomas, such as diffuse large B cell lymphoma and Hodgkin lymphoma. The role of PET/CT in lymphomas with variable FDG avidity, such as MZL, is still under active research. Aims: The purpose of this study was to evaluate PET/CT as a diagnostic and prognostic tool in patients with MZL. Methods: A retrospective cohort study of patients with newly diagnosed MZL, treated with immunotherapy, chemotherapy regimen, surgery or eradication between 2008 and 2016 in a single tertiary center. Patients who did not undergo pre-treatment PET/CT (P-PET/CT) were excluded. Patients were identified through the hospital's computerized database. Demographic, clinical and laboratory data were collected from patients' files until the latest follow-up available and for at least 12 months after completion of treatment administration. P-PET/CT, interim (I-PET/CT) and end-of-treatment PET/CT (E-PET/CT) studies were centrally reviewed by a nuclear specialist and reported using 3 methods of evaluation: visual assessment, maximal SUV reported and Deauville 5-point score (DS) evaluation (DS only for I-PET/CT and E-PET/CT). PET/CT was interpreted as positive if any of the three evaluation methods was positive. The primary outcome was to evaluate the prognostic role of P-PET/CT, I-PET/CT and E-PET/CT on progression free survival (PFS) and overall survival (OS). Survival curve was calculated using the Kaplan-Meier method, and Cox regression. Models adjusted for age, sex, and stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) was used for the association between PET/CT positivity, PFS and OS. Results: Data of 196 patients with MZL were identified. 86 patients were excluded due to absence of P-PET/CT. Thus, 110 patients were included in this analysis. The most frequent histological type of MZL was MALT (51%). Median patients' age was 67 years (range: 18-93). The median follow-up period was 63 months (range: 3-278). 54/110 (73%) presented with bone marrow involvement and 100/110 (91%) had extranodal involvement. MZL transformed to an aggressive lymphoma in 3% of the patients. The median OS and PFS for the whole cohort were 63 months (interquartile range: 39-85) and 60 months (interquartile range: 37-76), respectively. 77/110 (71.3%) patients had positive P-PET/CT. Among 19 patients that had I-PET/CT, eight studies were positive and 11 negative. 63/110 patients underwent E-PET/CT: 12 studies were positive and 51 negative. P-PET/CT and I-PET/CT were not predictive of PFS or OS. Sub-group analysis of the different types of MZL did not show such a correlation as well. When adjusted for age, sex and stage, positive E-PET/CT was associated with reduced PFS with a hazard ratio (HR) of 4.16 (CI 1.55-11.2, p=0.005) (Figure 1). Conversely, positive E-PET/CT did not correlate with OS maybe due to the low death rate (3 patients). In a univariate analysis, beta 2 microglobulin was prognostic for PFS with and adjusted HR of 1.44 (CI 1.08-1.94, p-0.014). Conclusions: Our study shows that above 70% of MZL are FDG avid. P-PET/CT and I-PET/CT were not predictive of PFS; However, E- PET/CT was predictive of PFS with an adjusted HR of 4.2. Figure 1: The association between E-PET/CT in PFS Disclosures No relevant conflicts of interest to declare.

Abstract Background Rituximab in combination with chemotherapy has been shown to improve overall survival (OS) in pts with FL compared with chemotherapy alone. The effect of MR was evaluated in randomized clinical trials (RCTs) with conflicting results regarding OS. In a previous systematic review and meta-analysis of summary (aggregate) data we demonstrated an OS benefit of MR treatment in pts with relapsed or refractory FL and an improved progression free survival (PFS) in both untreated and relapsed refractory FL. However, pts' disease and treatment characteristics may interact with the effect of MR. To improve identification of sub-groups of pts who may benefit from MR treatment, and to evaluate factors that interact with the effect of MR we conducted an international IPD (raw data) meta-analysis of RCTs of MR for pts with FL. We present the first analysis of this meta-database. Methods In June 2014, we updated an electronic search in Pubmed and the Cochrane Library, conference proceedings and database of clinical trials for randomized trials comparing MR to observation. The investigators of eleven trials that fulfilled inclusion criteria were invited to cooperate. Results of one trial were not reported and this trial could not be included in the meta-analysis. Seven study groups participated in this collaborative project and contributed data on individual pts, including disease characteristics, past treatment, response, survival and adverse events. We examined the effect of pt, disease and treatment characteristics by performing a series of Cox regression analyses stratified by trial. In a sensitivity analysis we combined the assessed log hazard ratios (HR) using a log-rank test for each study and combined the results using a fixed effect meta-analysis. Results We obtained data for 2323 patients randomized in 7 trials of MR compared to observation after induction therapy. The median follow up ranged from 28-114 months. The median age was 57 years (23 - 85 years), and 41% were older than 60 years. 50% of pts were women, 97% had WHO performance status 0-1; 1195 (53%) pts received CHOP/RCHOP, 453 (20%) CVP/R CVP; 1755 (77%) received rituximab containing induction; 33% of pts received 1st induction, 67% ≥2nd. Overall, pts less than 60 years of age (vs. ≥60 years) (p < 0.0001), and women (p = 0.001) had a better prognosis. There was no interaction between sex and the effect of MR (p = 0.65). Pts treated with MR had an improved OS compared to observation (HR 0.76, 95% CI 0.62-0.93, p=0.008, Figure). This was demonstrated also in a sensitivity analysis of 10 studies fulfilling inclusion criteria. There was no statistically significant heterogeneity of treatment effect between trials (p=0.15). In an analysis by treatment line (1st vs. ≥2nd), the estimated effect of MR among patients who received ≥2nd induction was HR of 0.70 (95% CI 0.55 - 0.91), compared to 0.90 (95% CI 0.65 - 1.25) among patients who received 1st induction. However, this difference was not statistically significant (p=0.25). Analysis by the inclusion of rituximab in induction demonstrated among patients who received rituximab in induction a HR of 0.82 (95% CI 0.63 – 1.06), and among those who received induction without rituximab a HR of 0.68 (95% CI 0.49 – 0.93). This difference was not statistically significant (p= 0.35). Analysis by chemotherapy regimen demonstrated an estimated effect for MR among patients who received RCHOP/CHOP of 0.79, 95% CI 0.58 – 1.06, and after RCVP/CVP of 0.65, 95% CI 0.42 – 1.02, with no statistically significant difference between these sub-groups (p = 0.50). Conclusions This is the first report of the collaborative group of maintenance therapy for FL patients. Based on individual patient data, this study demonstrated an improved OS with MR therapy for patients with FL. A sensitivity analysis with all 10 eligible trials supported these results. Results support the effectiveness of MR among patients after their 1st induction as well as after ≥2nd induction, and irrespective of inclusion of rituximab in induction, and the chemotherapy regimen. These results are consistent with those of the summary data meta-analysis that was previously published. The wider CI and lack of statistical significance within sub-groups could be attributed to the sample size. Figure: Pooled HR of death of MR compared to observation in patients with follicular lymphoma. In one study there were no events in one group and it is not represented in the forest plot. Figure:. Pooled HR of death of MR compared to observation in patients with follicular lymphoma. In one study there were no events in one group and it is not represented in the forest plot. Disclosures Vidal: Roche: unrestricted grant Other. Shpilberg:Roche: Consultancy, Research Funding.

AbstractWe evaluated the role of 18‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography ([18F] FDG‐PET) with computed tomography (CT) (PET/CT) as a diagnostic and prognostic tool in newly diagnosed marginal zone lymphoma (MZL) patients.This is a retrospective cohort study of patients with newly diagnosed MZL, treated with immunotherapy, chemotherapy regimens, surgery, or Helicobacter pylori eradication between 2008 and 2016 in a single tertiary center. Only patients who had a pretreatment PET/CT (P‐PET/CT) were included. P‐PET/CT, interim (I‐PET/CT), and end‐of‐treatment PET/CT (E‐PET/CT) studies were reviewed. P‐PET/CT results were reported using two methods of evaluation, qualitative and semi quantitative: visual assessment (VAS) and maximal standardized uptake value (SUVmax), and I‐PET and E‐PET results were reported by Deauville 5‐point score (DS) evaluation as well. Avidity of PET/CT was defined as abnormal uptake in any of these methods. The primary outcome was the prognostic role of P‐PET/CT, I‐PET/CT, and E‐PET/CT on progression‐free survival (PFS) and overall survival (OS).Data of 196 patients with MZL were identified, 110 of which had P‐PET/CT and were included in this analysis. Median age was 67 years (range 18‐93). The median follow‐up period was 63 months (range 3‐278). The median OS and PFS for the whole cohort were 63 (interquartile range 39‐85) and 60 (interquartile range 37‐76) months, respectively. The avidity of PET at baseline for the whole cohort was 70% (77/110 patients), for MALT lymphoma, 62.5% (40/64 patients), for NMZL, 76.4% (13/17 patients), and for SMZL, 82.7% (24/29 patients). When adjusted for IPI, sex, and comorbidities, positive E‐PET/CT was associated with reduced PFS with a hazard ratio (HR) of 3.4 (95% CI, 1.27‐9.14, P = 0.02). Positive E‐PET/CT did not correlate with OS. However, there were only three events. P‐PET/CT was not predictive of PFS or OS. Our study demonstrates that above 70% of MZL are FDG avid. Positive E‐PET/CT is a strong prognostic factor for PFS.