Raanani, Pia

ABSTRACT Oligo‐secretory and non‐secretory MM present a clinical challenge due to the difficulties in initial diagnosis, response to treatment assessment, and relapse detection. They are excluded from most clinical trials, which typically require measurable disease. We describe the characteristics and outcomes of 86 patients with secretory myeloma at diagnosis who developed an OSR, matched 1:1 to a cohort with secretory relapse (SR). With a median follow‐up of 9.3 years, 16.6% (48/289) of evaluable patients developed an OSR. Lower levels of light chains at presentation, and younger age are predictive of an OSR. The median OS since relapse of the OSR group was 4.01 (95% CI 1.625–6.395) versus 3.25 (95% CI 2.255–4.245) years in the SR control group ( p = 0.4). A third of our OSR cohort had a subsequent SR. We did not find any predictive factor for SR after OSR. The median OS of the subgroup of patients who developed a SR after OSR was 3.35 years (95% CI 1.541–5.159), versus 5.8 years (95% CI 2.072–9.528) in the group that remained oligo‐secretory ( p = 0.336). The median TTNT of the SR after OSR group was 1.68 years (95% CI 0.341–0.919) versus 4.58 (95% CI not reached‐not reached) in the group that remained oligo‐secretory ( p < 0.001).

Abstract Introduction: Though originating from different cell origins, several reports have described patients with the coexistence of chronic myeloid leukemia (CML) and paraproteinemias, mostly in patients treated with tyrosine kinase inhibitors (TKIs). Objective : To determine whether the prevalence of paraproteinemia in a large cohort of chronic phase (CP-) CML patients is higher than expected in the general population. Methods: We conducted a cross-sectional study among out-patient CP-CML patients treated in a tertiary medical center. Between February 2019 and May 2021 consecutive CP-CML patients who consented to the study, performed the following tests: quantitative immunoglobulin (Ig) levels, serum-free light chains (sFLC), serum protein electrophoresis (SPEP), and if abnormal also serum protein immunofixation (IFIX). The primary outcome was the prevalence of paraproteinemia among this cohort of CML patients. We conducted further analyses to evaluate whether various patient, disease and treatment-related variables are predictors of paraproteinemia within our cohort. Results: One hundred patients, 50% males, with a median age of 63.5 (range 26-91.6) years were recruited for the study. The median time from CML diagnosis to enrollment was 6.3 (range 0.1-23.5) years. Cohort's characteristics are depicted in table 1. Monoclonal (M-) protein was detected on SPEP and IFIX in eight patients (8%), whose median age was 66.8 (range 46-74) years. Among them, two patients had an abnormal sFLC, elevated IgG or IgA levels, on a bone marrow biopsy over 10% monoclonal plasma cells were present, and in the absence of myeloma defining events they were diagnosed with IgG-kappa and IgA-kappa smoldering multiple myeloma (SMM), respectively. The other six patients had normal sFLC ratio and characteristics compatible with low-risk monoclonal gammopathy of undetermined significance (MGUS). Six patients with a detectable M-protein were treated with a TKI [imatinib (n=2), dasatinib (n=3), bosutinib (n=1)] and two were in treatment-free remission (TFR). All continue observation for their paraproteinemia. None of the patients in our cohort was diagnosed with active MM. The presence of anemia was predictive of paraproteinemia, albeit with borderline statistical significance in both univariate (p=0.053) and multivariate analysis (p=0.069). Apart from anemia, no predictors for paraproteinemia were found among various other patient and disease related variables. Conclusions: This is the largest study describing the prevalence of paraproteinemia among CML patients. We found the prevalence of MGUS in CP-CML patients (6%) to be higher than in the general population above the age of 50 (3.2%), and a non-negligible prevalence of SMM (2%). Based on these data, we recommend considering screening for paraproteinemia coexistence in CML patients. Further studies and extended follow-up are needed to elucidate the true clinical significance of our findings. Figure 1 Figure 1. Disclosures Leader: Bayer: Honoraria; Leo Pharma: Honoraria; Novartis: Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Honoraria.

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.