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Autoimmune cytopenias (AICs) affect 5% to 9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs—ibrutinib, idelalisib, and venetoclax—have a prominent role in the treatment of CLL, but their impact on CLL-associated AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab, and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.

Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050 ). RESULTS We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of COVID-19 at 18F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an 18F-FDG–avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a “far-from-COVID-19” finding at PET/CT.

Introduction Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. Results The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%; COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%; grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%). Conclusions EVIDENCE is the first real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. Disclosures Molica: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Speakers Bureau. Sanna: Janssen: Consultancy; Abbvie: Consultancy; Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding; AbbVie: Honoraria, Other; AstraZeneca: Honoraria; Gilead: Honoraria. Reda: Abbvie: Consultancy; Astra Zeneca: Consultancy; Beigene: Consultancy; Janssen: Consultancy. Tafuri: Novartis: Research Funding; Roche: Research Funding; Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.

Introduction Non-pegylated liposomal doxorubicin (NPLD) is considered a good alternative to conventional doxorubicin for the treatment of older patients (pts) with aggressive lymphomas and/or at high risk for cardiological toxicity. The use of R-COMP for the treatment of older pts with DLBCL has been supported by several small retrospective studies . In this report we describe the characteristics and outcomes of pts who were prospectively enrolled in the Elderly Project (EP) and who were treated with R-COMP and compared them with pts treated with conventional R-CHOP. Methods. This analysis was conducted starting from the dataset of the EP study. The use of NPLD was allowed according to 648/96 law, treatment decision was left to physician discretion and was independent of frailty status. For the purposes of this analysis, we included all pts who were treated with full doses of R-CHOP and R-COMP. The study endpoint were progression free survival (PFS) and overall survival (OS). A propensity score analysis was conducted to account for the main confounding factors. Results Overall 691 out of 1163 pts of the EP were treated with R-CHOP (383; 55%) or R-COMP (308; 45%); median age was 71 and 76 years for R-CHOP and R-COMP, respectively (p < 0.001) (Table 1). Pts were similarly distributed among different IPI groups for R-COMP or R-CHOP. Based on simplified Geriatric Assessment (sGA) 88%, 11% and Conclusions Data from the prospective observational EP study did not show significant differences in terms of efficacy comparing R-COMP to standard R-CHOP. The higher frequency of UNFIT and FRAIL pts among those treated with NPLD suggests R-COMP is a good strategy to offer a curative treatment to these groups of pts. Figure 1 Figure 1. Disclosures Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cavallo: ROCHE: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Gilead: Speakers Bureau. Fabbri: Servier/Pfizer: Honoraria; Takeda: Other: Travel, Accomodations, Expenses; Takeda: Honoraria. Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Ferrero: Incyte: Membership on an entity's Board of Directors or advisory committees; Morphosys: Research Funding; Gilead: Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau; Takeda: Other: travel expenses, accommodation. Nassi: Takeda: Consultancy; Kyowa Kirin: Consultancy; Incyte: Consultancy; Roche: Consultancy. Musuraca: Janssen, Incyte, Roche: Consultancy; Janssen, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen, Roche, Incyte: Honoraria. Flenghi: Janssen: Other: Travel, Accomodations, Expenses; Roche: Other: Travel, Accomodations, Expenses. Marcheselli: sandoz: Membership on an entity's Board of Directors or advisory committees. Luminari: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Other: Travel, Accomodations, Expenses; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; GENELAB SRL: Consultancy.

Introduction: Management of elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL) is challenging. A simplified Comprehensive Geriatric Assessment (sCGA) based on ADL (Activity of Daily Living), IADL (Instrumental ADL) and CIRS-G (Comorbidity Index Rating Scale for Geriatrics) scales has demonstrated to be better than clinical judgement to stratify patients' outcome but has never been included in initial assessment. To further assess the impact of sCGA on patients' outcome, we conducted a prospective observational study on a large series of elderly patients with DLBCL. Methods: Patients were enrolled if 65 year old or older, with an untreated de novo DLBCL. sCGA was available at a web based platform that classified patients as FIT, UNFIT, and FRAIL, as shown in Table 1. Treatment choice was left at physician discretion. According to anthracycline dose, therapy was classified as curative (≥70% of full anthracycline dose), intermediate ( Results: From December 2013 to December 2017, 1353 patients have been registered by 37 centres and 1207 were eligible. Median age was 76 years (65-94), 68% had stage III-IV, and 55% had an International Prognostic Index(IPI) ≥3; 500 (42%), 304 (25%), and 403 (33%) were classified as FIT, UNFIT and FRAIL, respectively. Data on treatment were available in 1164 patients: rituximab was used in 96% of patients; treatment was curative in 89%, 53%, and 36% of FIT, UNFIT, and FRAIL patients, respectively; intermediate in 10%, 39%, and 31%, palliative in 0%, 8%, and 33% of patients. The OS was available in 1158 out 1164 cases. With a median follow up of 30 months (1-59) 3y-OS was 64% (95% CI 61% to 67%). According to sCGA the OS was significantly different among the 3 geriatric groups. Correlation with OS was improved when sCGA was integrated with age < or ≥ 80 years to define 3 groups of patients (Table 2): FIT and UNFIT younger than 80 years (sCGA Group 1; 55%, 3 yr OS 75%), UNFIT ≥ 80 years and FRAIL younger than 80 years (sCGA Group 2: 28%, 3yr OS 58%), FRAIL ≥ 80 years (sCGA Group 3: 17%; 3yr OS 43%). Univariable and multivariable analysis for OS was conducted using the 3 sCGA groups and other clinical and laboratory features. The 3 sCGA groups were shown as independent prognostic factors with IPI and with anemia (Hb < 12 g/dl). We used results of multivariable analysis to build a categorical prognostic index assigning different weights to prognostic features based on their Hazard Ratio (HR) (Table 3). The Elderly Prognostic Index (EPI) was defined as the score obtained from the sum of the weights and allowed to define 3 risk groups: Low Risk (LR: score 0-1; 23% of patients); Intermediate Risk (IR; score 2-4; 48%); High Risk (HiR; score 5-7; 29%). The 3 EPI risk groups had a different 3 year OS of 87%(95%CI 81-91), 69%(95%CI 63-73), and 42% (95%CI 36-49); HR for IR vs LR 2.57 (1.72, 3.84); HiR vs LR 6.21(4.17 -9.25), HiR vs IR 2.42 (1.91-3.05) (Figure1). Regarding treatment modality, curative, intermediate and palliative therapies were adopted in 89%, 10%, and 1% of the LR group; 70%, 24%, 7% of the IR group, and 37%, 35%, 28% of the HiR group. The model was internally validated by means of 1000 procedures confirming good performance (slope shrinkage 0.935 and c-Harrell 0.675 in validation sample compared with 0.682 in training sample). The EPI was also tested in an external validation data set that was identified from the pivotal study of sCGA in DLBCL (N=172 patients, Tucci A. et al, Leuk Lymph, 2015) (Figure 1). Conclusion: Using data from this large prospective observational study on elderly DLBCL patients we were able to build a new prognostic index that allows to identify 3 risk groups with significant differences in terms of 3 years OS. The EPI is the first index that integrates geriatric assessment with clinical features and contributes to improving management and clinical research in elderly patients with DLBCL. Disclosures Spina: Servier: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Sandoz: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other; Roche: Other: lecture fee; Teva: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; GILEAD: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Celgene: Other: lecture fee; BMS: Other: lecture fee; Sanofi Genzyme: Other: lecture fee; CTI: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Menarini: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee, Research Funding; Takeda: Other: lecture fee; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Pfizer: Membership on an entity's Board of Directors or advisory committees. Merli:Janssen: Honoraria; Takeda: Honoraria, Other: Travel Expenses; Gilead: Honoraria; Mundipharma: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses. Cavallo:Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Ladetto:Roche: Honoraria; AbbVie: Honoraria; J&J: Honoraria; Celgene: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Chiappella:Celgene: Other: advisory board, Speakers Bureau; Janssen: Other: advisory board, Speakers Bureau; Servier: Other: advisory board, Speakers Bureau; Roche: Speakers Bureau; Teva: Speakers Bureau. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Ferrero:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau; Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees. Luminari:ROCHE: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant; GILEAD: Other: Lecturer; TAKEDA: Other: Travel Grant.

Autoimmune cytopenias (AIC) affect 4-7% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs (i.e. ibrutinib, idelalisib and venetoclax) have recently entered the therapeutic armamentarium for CLL showing excellent results in terms of efficacy. The activity of these compounds in CLL-associated AIC is largely unknown, due to the exclusion of patients with active AIC from the pivotal clinical trials and to the paucity of studies directly investigating the role of these novel inhibitors in this setting. Also, no guidelines are available to direct the management of patients who develop AIC during the treatment with targeted drugs. The purposes of this study were 1) to evaluate the characteristics and outcome of pre-existing AIC in patients with CLL treated with ibrutinib, idelalisib or venetoclax in the real-life setting, and 2) to describe the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs. We retrospectively collected data from patients with CLL treated with ibrutinib (n=379), idelalisib (n=100), or venetoclax (n=49) in 11 Italian centers. AIC status was defined as active when it was not controlled with current medical management, controlled/improved when blood counts did not reach the normal values or if subclinical hemolysis was still present, and resolved in the presence of a complete blood count normalization. Pre-existing AIC was reported in 38/379 (10%) of ibrutinib-treated patients, 20/100 (20%) of idelalisib-treated patients and 6/49 (12%) of patients who received venetoclax (Table 1). At the time of the start of ibrutinib, pre-existing AIC was considered active in 8/38 (21%) patients, controlled in 11/38 (29%) and resolved in 19/38 (50%). Among patients with active AIC, ibrutinib treatment induced AIC improvement in 1 patient and a resolution in 4. In addition, during ibrutinib treatment, in 1 patient active AIC was initially controlled but subsequently relapsed at CLL recurrence, in 1 patient concomitant steroid administration was required to maintain AIC controlled and in 1 patient AIC remained stable without needing additional therapy. Controlled AIC remained stable in 3 patients, improved in 3 and resolved in 5. Among 19 patients with a resolved AIC at the time of the start of ibrutinib, only 1 had an AIC relapse during ibrutinib therapy, which was successfully managed with steroids. At the time of the start of idelalisib, pre-existing AIC was considered active in 5/20 (25%) patients, controlled in 7/20 (35%) and resolved in 8/20 (40%). During idelalisib treatment, AIC improved in 2 patients with active AIC and in 1 patient with controlled AIC, and resolved in 2 patients with active AIC and in 5 patients with controlled AIC. No recurrence was observed in 7/8 patients who had resolved AIC at the time of the start of idelalisib. Overall, a recurrence or worsening of a pre-existing AIC occurred in 3/20 patients. In the venetoclax cohort, at treatment initiation, pre-existing AIC was active in 2/6 (33%) patients, controlled in 1/6 (17%) and resolved in 3/6 (50%). Active AIC resolved with venetoclax treatment in 1 patient and improved, albeit with concomitant steroid therapy, in the second. The patient with controlled AIC remained stable but needed additional AIC-directed therapy. AIC recurrence was observed in 1/3 patients with resolved AIC and was successfully treated with steroids. Regarding treatment-emergent AIC, they occurred in 8/379 (2%) patients during ibrutinib therapy, in 4/100 (4%) during idelalisib and in 7/49 (14%) during venetoclax (Table 1). Treatment-emergent AIC significantly correlated with pre-existing AIC in the three cohorts (p In conclusion, this study based on a large, multicenter, retrospective real-life analysis shows that 1) ibrutinib, idelalisib and venetoclax can induce an improvement or even a resolution of pre-existing AIC in CLL patients, and that 2) treatment-emergent AIC during targeted drugs administration is a rare event, which in most patients is manageable without requiring treatment interruption. Disclosures Trentin: ABBVIE: Honoraria, Other: board; Janssen: Consultancy, Honoraria, Other: Board; gilead: Consultancy; Roche: Honoraria, Other: Board. Tedeschi:Janssen spa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; SUNESIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Mauro:Roche: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Foà:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Boccadoro:Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding. Coscia:Karyopharm Therapeutics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC = 68) or reduced (reduced intensity conditioning (RIC) = 29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n = 60) or in > 2nd CR or active disease (advanced phase: n = 37). With a median time of 21 days (range 12-38 days), the cumulative incidence (CI) of neutrophil engraftment was 94 ± 3%. The 100-day CI of III-IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9 ± 3% and 12 ± 4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3-5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53 ± 7 vs 24 ± 8% (P = 0.006) and 48 ± 7 vs 22 ± 8% (P = 0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36 ± 6 vs 28 ± 9%) while the relapse risk was lower for the MAC patients (22 ± 6 vs 45 ± 11%), who showed higher OS (48 ± 7 vs 29 ± 10%) and DFS (43 ± 7 vs 26 ± 10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.

To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8). Twenty-two patients received bendamustine alone and 87 patients received R-B (median B dosage: 100 mg/m(2) per day, range 90-130 mg/m(2) per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R-B (P = 0·014) and in those responsive to the previous treatment (P=0·04). After a median follow-up of 7·9 months (range 1-148), the median progression-free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response (P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4-7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R-B was an effective and well-tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity.

We conducted a population-based study of peripheral lymphomas (PL) that had been diagnosed between 1997 and 2003 in the province of Modena, Italy, with the aim of providing updated incidence, clinical and survival data for these cancers. We evaluated the incidence patterns and time trends of 1582 cases of PL that had been reclassified according to the WHO classification of hematological malignancies. Data regarding clinical characteristics, treatment and outcome were also collected for each case. The World Age-Standardized Rate (ASR) was calculated as 13.4, 2.2 and 3.4 per 100,000 people for B-cell non-Hodgkin's lymphoma (NHL), T-cell NHL and Hodgkin's Lymphoma (HL), respectively, with an increase of 1.62% per year during the study period. The lymphoma subtype showing the highest incidence was found to be diffuse large B-cell lymphoma (DLBCL) with an ASR of 4.8. Compared with reports from other western countries, our series is characterized by a higher incidence of HL and indolent B-NHL in general, and of CLL/SLL (ASR = 3.3) and marginal zone NHL (ASR = 1.5), in particular, and also by a lower incidence of FL (ASR = 2). After a median follow-up of 54 months, the 5-year relative survival for the whole series was found to be 70% with a statistically significant improvement for cases diagnosed during 2002-2003 (from 66 to 74%; p = 0.03). Survival improvement within the study period was also evident for patients with DLBCL, HL and T-NHL. Our study provides a comprehensive description of both the epidemiological and clinical features of PL cases in Modena and our data also reflect the major advances in the curability of some histological subtypes of this disease. The usefulness of a population-based approach to better characterizing different lymphoma subtypes is also demonstrated.

Over a period of 28 months, we observed five cases of osteonecrosis of the jaw (ONJ) in cancer patients treated with bisphosphonates (BP) at our institution. This prompted us to undertake a retrospective, multicenter study to analyse the characteristics of patients who exhibited ONJ and to define the frequency of ONJ in multiple myeloma (MM). We identified 35 cases in Gruppo Italiano Studio Linfomi centers during the period 2002 - 05. The median time from cancer diagnosis to the clinical onset of ONJ was 70 months. In these 35 cases of ONJ, 24 appeared 20 - 60 months after starting BP treatment. The time for the onset of ONJ was significantly shorter for patients treated with zoledronic acid alone than for those treated with pamidronate followed by zoledronic acid. The frequency of ONJ in the MM group during the study period was 1.9%, although the nature of the present study may have resulted in an underestimation of ONJ cases. Our analysis strongly suggested an association between the use of BP and the occurrence of ONJ, although we were unable to identify any definite risk factors with a retrospective study. The most frequently ONJ-associated clinical characteristics were chemotherapy treatment, steroid treatment, advanced age, female sex, anemia, parodonthopaties/dental procedures and thalidomide (in the case of MM patients).

The Intergruppo Italiano Linfomi started, in 1996, a randomized trial for the initial treatment of elderly patients (older than 65 years) with Diffuse Large B-Cell Lymphoma (B-DLCL) comparing 6 courses of Mini-CEOP vs 8 weeks of P-VEBEC chemotherapy. Study objectives were survival, response and Quality of Life (QoL). Two hundred and thirty-two patients were evaluable for final analysis. Complete Response (CR) and Overall Response Rates (ORR) were 54% vs 66% (p = 0.107) and 90% vs 78% (p = 0.021) for P-VEBEC and Mini-CEOP, respectively. With a median follow-up of 72 months, the 5-year Overall Survival (OS), Relapse Free Survival (RFS), and Failure Free Survival (FFS) were 32%, 52%, and 21%, respectively. Subjects achieving a CR showed improvement of QoL regardless of treatment arm. Both Mini-CEOP and P-VEBEC determined a similar outcome for elderly patients with B-DLCL, with a third of patients alive after more than 6 years of follow-up. Both regimens can be considered equally for combination treatment with anti-CD20 monoclonal antibody.

Despite recent therapeutic advances, primary central nervous system lymphoma (PCNSL) shows the worst prognosis among all non-Hodgkin lymphomas (NHLs), with a 5-year survival rate ranging from 4 to ...

Background —Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F 2 -isoprostane 8-iso-prostaglandin (PG)F 2α , a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation. Methods and Results —Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF 2α and 11-dehydro-thromboxane B 2 (TXM), an in vivo index of platelet activation. Sixty-two had non–insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF 2α in this setting. Urinary 8-iso-PGF 2α excretion was significantly higher ( P =0.0001) in NIDDM patients (419±208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208±92; 41 to 433). Urinary 8-iso-PGF 2α was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF 2α excretion was also significantly ( P =0.0001) higher in IDDM patients (400±146; 183 to 702) than in control subjects (197±69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF 2α (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant ( P =0.0001) reduction in 8-iso-PGF 2α and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF 2α was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion. Conclusions —We conclude that DM is associated with increased formation of F 2 -isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Abstract 3747 Poster Board III-683 Background despite the prognosis of aggressive non-Hodgkin Lymphoma has considerably improved over the past decades, the treatment of elderly patients with NHL is still a difficult challenge for the clinician. A retrospective EORTC study conducted in patients with aggressive NHL and age above 70 years showed that about half of patients received an aggressive treatment and that only 15% of investigators employed full-dose regimens from the first cycle. We here present the preliminary data of CHOP-like regimen delivered as first-line or salvage therapy to elderly or young patients with NHL and not eligible for more aggressive therapy. Patients and methods from July 2006 to January 2009, 27 pts (M/F:11/16) with a median age of 71 years (range: 53-84) were included in the study. Twenty-four pts (88%) were more than 65 yo, 18 (66%) had high-grade and 9 (34%) an indolent lymphoma. Stage III-IV disease according to Ann Arbor staging occurred in 18 pts (66%) whereas aaIPI, evaluated only for pts with aggressive NHL, was 3 2 in 9 pts (18%). ENS involvement ≥ 1 was present in 11 (41%) and BM involvement in 13 pts (48%). Most of pts (60%) had ECOG PS ≥ 1. Twenty out of 27 pts (74%) received COMP±R as first-line treatment and 7 (26%) as salvage therapy; all but one of pre-treated pts had received more than 1 line of chemotherapy (range 2-4). Twenty-five (92%) pts had co-morbidity with more than 1 disease in 44% of cases. Median LVEF was 59% (range: 35-80%). COMP±R regimen consisted of cyclophosphamide 750 mg/m2 IV d1, vincristine 1.4 mg/m2 IV d1 (capped at 2mg), liposome-encapsulated doxorubicin (MyocetÒ) at the dose of 50 mg/m2 IV d1 and Prednisone 100 mg/die PO d 1-5 with or without Rituximab at dose of 375 mg/m2 d8 at first course and at d1 of subsequent courses according to B or T-cell lymphoma phenotype respectively. To pts with early stage disease were planned 4 courses of COMP±R±IF-RT while those with advanced stage of disease received six courses of chemotherapy delivered every 3 weeks. Median number of cycles delivered was 5.6 (range: 4-8). All patients completed the planned treatment and most of them (92%) received G-CSF at dose of 300 mg/die as primary (67%) or secondary (25%) prophylaxis. ESA support was need in 8 pts (30%). Results complete response (CR) was achieved in 21 (78%) and partial response (PR) in 3 (11%) of pts with an ORR of 89%; three pts had stable (n=2) or progressive disease (n=1). The regimen was safe and well tolerated with dose reduction occurring in 9 pts (34%). None of pts developed cardiac toxicity. The mainly adverse events recorded was neutropenia occurring in 15% of pts and febrile neutropenia in 6 pts (23%). Extra-haematological toxicity was mild (WHO grade 1-2) and recorded in 18% of pts. There was no treatment-related fatal toxicity. With a median follow-up of 15 months (range 6-33) the OS and EFS was 93% and 89% respectively. Conclusion COMP±R regimen shows to be safe and effective in a group of elderly patients both as first line or salvage therapy. However more patients and longer follow-up is required to assess definitively the role of this regimen in elderly patients with untreated aggressive NHL. A prospective phase II trial is ongoing at our Institution. Disclosures: No relevant conflicts of interest to declare.

Abstract 4795 Introduction Radioimmunotherapy (RIT) has emerged as an important treatment options for patients with non-Hodgkin lymphoma (NHL). Yttrium-90 ibritumomab tiuxetan (Zevalin®) consist of ibritumomab, a murine monoclonal antibody to CD20, conjugated to the metal chelator tiuxetan for retention of the beta emitter Yttrium-90. Clinical trials with this agent have demonstrated significant activity in indolent NHL with mild toxicity. The median age of NHL patients included in these trials is mainly < 65 years. Our aim was to evaluate the effectiveness of Zevalin as treatment option for patient > 65 years old with indolent NHL. Patients and Methods Between November 2005 to June 2009 fifteen patients, five males and ten females, median age 76 years (range 67-82), with indolent NHL (13 follicular and 2 small lymphocytic) were treated with Zevalin. Six patients had stage IV disease, five stage III and four stage II. All patients received an initial infusion of rituximab at a dose of 250 mg/m(e)2 on day 1 and a second infusion at same dose on day 8 followed by a weight-based dose of Zevalin (median dose 1006 MBq; range 668-1260). Eight patients perfomed Zevalin as consolidation after first line therapy with Rituximab plus chemotherapy (6 R-CHOP, 1 R-FN, 1 R-COMP): of these three were in complete remission (CR) and five in partial remission (PR). Seven patients perfomed Zevalin in relapse (four in first and three in second relapse). Results After RIT 13 of 15 patients were evaluable. Overall response rate was 92% (10 CR, 2 PR); in particular all patients in first line of treatment achieved CR. One patient had stable disease. At a median follow-up of 15 months (range 2-34), all patients are alive in persistent CR or PR. One of two patients in PR achieved CR after successive therapy. Treatment was well tolerated; transient thrombocytopenia (grade 3-4) was seen in 9 patients and transient neutropenia (grade 3-4 ) in 6 patients. Only one patient developed herpex-zoster virus infection. Conclusion In our experience, Zevalin produces high response rate (up to 90%) and durable remission without severe toxicity in older patients with indolent NHL. Notably, in first-line treatment, RIT resulted in PR-to-CR conversion in all five patients in PR after the R-chemotherapy. The favourable safety profile of this regimen makes it an effective consolidation treatment for older patients who, because of age and comorbidity, are not eligible for intensive treatment as high-dose therapy and stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Background and aim: In the last decade HDT-ASCT has significantly improved progression-free and overall survival of patients with MM. Achievement of CR or good partial response and the tumor reduction attained with the induction pretransplant chemotherapy have been shown to be the most relevant prognostic factors for long-term survival. In recent years, novel drugs such as thalidomide and bortezomib have been introduced in the treatment of MM. Bortezomib (B) (VelcadeÒ) as a single agent, gives a response rate ranging from 35% to 50%, including up to a 9% CR rate in relapsed/refractory patients, and of 40%, with a 10% CR rate in the up-front setting. Thalidomide (T) has been identified as the first independently active agent in MM since the introduction of melphalan and prednisone and currently represent the milestone of initial treatment in elderly patients. Since B and T target different molecular pathways, we started a phase II trial in order to assess efficacy, toxicity and rate of PBSC collection after VTD regimen delivered as induction pretransplant chemotherapy in patients with newly diagnosed MM. Patients and Methods: from June 2007 to July 2008 14 pts (M/F: 11/3) with a median age of 56 years (range: 42–71) were enrolled in the study; six pts (43%) were more than 60 yo and 7 pts had a previous history of M-GUS lasting in median 54 months. At time of treatment there were 71%, 22% and 7% having Durie and Salmon staging III, II and I respectively, while ISS was 1 in 22%, 2 in 50% and 3 in 28% of cases. One pt had renal impairment, extensive bone disease was documented in 78% of cases with 2 pts showing extramedullary disease. Sixty-five percent of pts (9/14) had IgG MM, 14% IgA, 7% light chain, and 14% non secretory myeloma. Unfavourable cytogenetic was recorded in 36% (5/14) of cases. Bortezomib was administered at 1.3 mg/m2 on days 1,4, 8, 11 as short IV infusion, thalidomide at daily dose of 100 mg PO and Dexamethasone (40 mg/die PO) the day of bortezomib infusion and the day after (640 mg for each cycle) every 4 weeks for 3–4 courses. All patients received deep venous thrombosis prophylaxis consisting of aspirin 100 mg daily (44%), low molecular weight heparin (28%) and low dose warfarin (28%). Following VTD regimen patients underwent to high-dose cyclophosphamide (4 g/m2) with G-CSF support and peripheral stem cell harvest. MEL 200 was given as conditioning regimen. All patients received standard dose of zoledronic acid monthly. Results: At present time all patients are evaluable for VTD and PBSC collection while 10 for response after transplant. After 3 courses of VTD 93% of pts achieved more than a partial response including 57% of CR and 36% of VGPR. One pt achieved a PR. VTD regimen resulted well tolerated with main toxicity consisting of WHO grade III peripheral neuropathy recorded in 37 % of pts. There were no pts with relevant hematologic toxicity or other non-hematologic toxicities and there were no chemotherapy reduction or delay because of toxicity. None of pts developed DVT. A sufficient amount of CD34+ cells (median 6.5 × 106/kg; range: 2.7–11.6) was collected in 13 of 14 evaluable pts after a median of 1.4 aphaeresis (range:1–2). One pt failed to collect after CTX and was treated with HD-Ara-C obtaining an adequate number of CD34+ cells for transplant. The median CD 34+ cells infused in the 10 transplanted pts was 3.3 ×106/kg (range: 2.0 – 4.7). Times to platelet (20×109/L) and granulocyte (500×109/L) recovery were 13 and 10 days respectively. After HDC and ASCT 7 of 10 patients presented CR (70%) and 2 (20%) a VGPR with an ORR of 90%. One pt presented progression disease after 6 months from transplant. Conclusion: these very preliminary data suggest that VTD regimen given as pretransplant chemotherapy is effective and well tolerated regimen; the capacity to give high response rate in a short time without to compromise PBSC collection makes VTD regimen a good option for initial treatment of newly diagnosed MM patients although more pts and longer follow-up are needed to assess the real impact on survival of this regimen.

The achievement of a clinical response to the first part of induction chemotherapy has been considered for predicting survival in patients with aggressive non Hodgkin lymphoma (NHL). In April 2000, the Gruppo Italiano Studio Linfomi (GISL) started the LA05 trial with the aim of assessing different treatment modalities according to response to 4 initial courses of chemotherapy (CT) assessed according to the international response criteria for NHL. Untreated Patients younger than 65 years with histologically confirmed diagnosis of aggressive NHLs were eligible to the study. All stages and all IPI groups were allowed. After 4 courses of CT patients achieving at least a PR >75% were to be treated with two additional courses of CT (group 1); those achieving PR 75%, 49 (19%) achieved a PR 75% was 74%, 62% and 42%, for patients with an initial IPI of 0–1, 2 or 3+. At the end of treatment program, a CR was achieved in 57% of cases and a PR in 14%. After a median follow-up of 21 months (range 1–73), the 2-year OS was 69% (IC 95% 62–75), being 85%, 65% and 25% for group 1, 2 and 3 respectively (p75% after the first part of initial CT overcomes the prognostic role of IPI in patients with aggressive NHL.

The incidence of lymphomas has increased in many parts of the world in recent decades. We conducted a population-based study of peripheral lymphoma (PL) in the province of Modena (Italy). According to the international classification for lymphomas (WHO/ICD-O-3) we evaluated incidence patterns and time trends of 1,582 cases of PLs diagnosed between 1997–2003, also providing details of clinical characteristics, treatment and outcome of different entities. World Age Standardized Rates (ASR) varied substantially among lymphoid neoplasm subtypes. Overall, ASR (per 100,000) was 13.4 for B-cell lymphomas (16.5 and 10.6 for males and females respectively), 2.2 for T-cell lymphomas (3.1 and 1.5) and 3.4 for Hodgkin lymphoma. Among B-NHL the highest ASR was observed for Diffuse large B-cell lymphoma (DLBCL, 4.8) and Small lymphocytic lymphoma (CLL/SLL, 3.3). Among T-cell lymphomas, ASR was 1.4 for Mycosis fungoides/Sezary syndrome (MF/SS) and 0.4 for both Peripheral T-cell lymphoma (PTCL) and Anaplastic large cell lymphoma (ALCL). The overall annual percent change (APC) of the World ASR was 1.62 (C.I.95%: −4.32; 7.93). Extranodal (EN) involvement was observed in 49% of cases; a diagnosis of Primary EN lymphoma (PENL) was confirmed in 27.8% of cases. In addition to MF/SS, the most frequently reported PENL were marginal zone lymphomas (MZL) and DLBCL. The documented five years Overall Survival (OS) for the whole series was 61.9%, being 61.7%, 55.3% and 83% for B-NHL, T-NHL and HL, respectively. These data confirm an overall improvement when compared with available historical controls for the main European countries. In addition, using period analysis we could estimate more up-to-date survival data within our studied series (all patients vs those diagnosed after 2002): survival of patients with MZL, DLBCL and HL strongly improved during the study period. Among different lymphoma subtypes, patients with Hairy cell leukemia (HCL), HL and MF/SS had the best survival with 5-year OS of 94%, 83% and 82%, respectively. In particular, for HCL and MF/SS the analysis of the Relative Survival suggested that there was no substantial difference in survival compared with healthy population. Our study provides a comprehensive description of both epidemiological and clinical features of PL in the province of Modena, recognizing in a population-based approach, major advances in the curability of some histological subtypes.