Gurion, Ronit

PURPOSE The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival (PFS), but without improvement in overall survival (OS), likely because of toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL. METHODS Patients 65 years and older with previously untreated MCL received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus six cycles of bendamustine (90 mg/m 2 once daily; days 1 and 2) and rituximab (375 mg/m 2 as a single dose; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. The primary end point was PFS per the independent review committee; overall response rate and OS were secondary end points. RESULTS In total, 598 patients were randomly assigned, with 299 in each arm. At a median follow-up of 49.8 months using the reverse Kaplan-Meier method, the median PFS was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.94]; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. OS was not significantly different (HR, 0.86 [95% CI, 0.65 to 1.13]; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively. CONCLUSION The combination of acalabrutinib with bendamustine-rituximab significantly improved PFS. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.

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.

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.