ALBERT

Description: Abstract 3879 Purpose. The use of early (interim) positron emission tomography (PET) restaging during front-line therapy in Hodgkin's lymphoma (HL) has considerably increased in clinical practice as an early recognition of treatment failure allows patients to be addressed to more intensive treatment regimens. Patients and Methods. Between June 1997 and June 2009, 304 newly-diagnosed Hodgkin's lymphoma patients (147 early-stage and 157 advanced-stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent to a PET staging and restaging at baseline, after 2 cycles of therapy and at the end of the treatment. Results. 53 patients showed a positive interim PET and only 13/53 (24.5%) achieved a complete response (CR), whereas 251 patients showed a negative PET and 231/251 (92%) remained in CR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival (p=0.0000) and 9-year overall survival (p=0.0000), with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET and only 4 (21%) achieved a CR; among the 128 negative interim PET patients, 122 (97.6%) obtained a CR. In the advanced-stage subset, 34 patients showed a persistently positive PET (with only 9/34, 26.4% in CR), whereas 123 showed a negative interim PET, with 109 (88.6%) remaining in CR. Conclusions. Our results confirm the role of early PET as a significant step forward for the management of both early and advanced-stage HL patients, offering the potential for an immediate switch to high-dose treatments, if required. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3890 Introduction: Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy. Nevertheless a small proportion of patients with localized stage do not respond to therapy and progressed. We want to explore the predictive value on therapy outcome of an early evaluation of treatment response by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan performed after two corses of ABVD in pts with localized Hodgkin's disease. Patients and methods: From 2002, 246 new localized stage cHL pts were consecutively admitted to twelve Italian hematological centers on behalf of Intergruppo Italiano Linfomi. Pts with stage I-IIA according to Ann Arbor stage, independent of presence of bulky disease, were considered for the study. FDG-PET was mandatory at baseline, after two cycles and at the end of therapy. International Harmonization Project (IHP) interpretation criteria were recommended to define PET positivity. We evaluated the progression free survival of pts starting from the time of diagnosis to relapse or progression of disease or last follow-up. No treatment variation based only on PET-2 results was allowed. All bulky-disease pts reports were centrally reviewed. Results: The median age was 33 years (13-78), 133 pts were female, 225 pts were stage II, bulky was reported in 76 pts, 231pts were treated with combined modality and 15 pts were treated with chemotherapy alone. The FDG-PET performed after two cycles (PET2) was positive in 32 pts (13%). Seventeen non-bulky pts were PET2 positive: 10 (59%) progressed or relapsed and 7 remained in CR. By contrast 152/153 (99%) non-bulky pts with a negative PET2 remained in CR. Thus the PPV value of a PET2 in non-bulky pts was 59% and the NPV was 99%, moreover the sensitivity and specificity of PET2 were 91% and 96%, respectively. In bulky disease pts we performed a revision of all reports according to Deauville criteria and 3 cases were converted from PET2 positive to PET2 negative. In revised bulky disease pts 15 were PET2 positive: 6 (40%) progressed or relapsed and 9 remained in CR. In this group of pts the PPV was 40%, the NPV 93% and sensitivity and specificity were 60% and 90% respectively. In univariate analysis negative FDG-PET performed after two cycles (p .0000), absence of bulky disease at diagnosis (.005) were statistically correlated with a better progression free survival. In multivariate analysis only PET2 was independently predictive of relapse/progression probability (p .000). With a median follow-up of 35 months (range 4–87), the 2-yr FFS probability for PET2 negative and for PET2 positive non-bulky patients were 98% and 29% respectively (p: .000) for patients with bulky-disease were 99% and 45% respectively (p: .002). Conclusion: This multicentric study confirms that FDG-PET scan performed after two courses of conventional standard dose chemotherapy was able to predict treatment outcome in early stage non-bulky cHL. In bulky disease we suggest new interpretation criteria to define interim PET results. Disclosures: Vitolo: Roche: Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 154 Background Follicular lymphoma (FL) has an indolent course during which patients (pts) receive multiple lines of active treatments ranging from single-agent chemotherapy (CHT) or monoclonal antibodies (MoAb), to high-dose therapy with stem cell transplantation (HSCT). In relapsed patients the efficacy of salvage treatments may be affected by the type and the intensity of the previous treatments and it is currently not known whether a definite sequence of treatments throughout the course of the disease could optimize the outcome of patients. Since randomized trials can hardly be designed to answer this important clinical question, the Fondazione Italiana Linfomi (FIL) launched an observational, multicenter, retrospective study (REFOLL) to analyze if combinations of different first-line and salvage treatments could be identified, able to achieve a better long-term outcome. Patients and Methods Of 582 pts with FL at first relapse between 2000 and 2008 registered from 25 Institutions, 548 were included in the study. They had received either alkylating- (AA) (22%), or anthracycline- (AC) (61%) or nucleoside analogues-based (NA)(17%) CHT as first-line treatment, with the addition of rituximab (R) in 284 (52%). AA pts were older (PCHT with R showed a better outcome than CHT -〉CHT without R (HR:0.55, P=0.015; HR 0.61, P=0.047 after adjusting by age and stage at diagnosis). Conclusions Auto-HSCT obtained the best TTNT after relapse compared to any other regimen but its efficacy was maximized when anthracycline-containing CHT was used as first-line treatment, compared to other CHT programs. The addition of R to first-line CHT did not adversely impact on the results of any salvage. This study supports the concept that different sequences of active treatments do not necessarily obtain similar long-term results, which is important in the management of indolent diseases like FL and warrants further studies. The sequence of AC-CHT at diagnosis and auto-HSCT at relapse may be tested as the reference sequence of active treatments in FL patients. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: we previously reported (Vitolo U, JCO 2013) the results of a randomized study with brief first-line chemoimmunotherapy followed by rituximab maintenance vs observation. With a median follow-up of 42 months, 3-year Progression Free Survival (PFS) and Overall Survival (OS) were 66% and 89%, respectively. The addition of Rituximab maintenance gave a benefit to the patients: 2-year PFS was 81% for rituximab maintenance versus 69% for observation with a HR of 0.63 (95% CI: 0.38-1.05, p=0.079), although not statistically significant. Moreover we also found that achievement of Minimal Residual Disease (MRD) negativity predicted a better PFS: 3-year PFS 72% vs 39%, HR 3.1 (Ladetto M, Blood 2013). Overall these data showed the good efficacy of this brief chemoimmunotherapy regimen in elderly FL patients. Aim of this analysis was to report long-term outcome and long-term toxicities of this regimen. Methods: From January 2004 to December 2007, 242 treatment-naive patients aged 60-75 years with FL Grade I, II and IIIa were enrolled by 33 FIL centres. Patients had to have advanced (high tumor burden stage II or stage III-IV) disease requiring treatment: 4 monthly courses of R-FND (standard doses of Rituximab, Fludarabine, Mitoxantrone, Dexamethasone) every 28 days followed by 4 weekly Rituximab infusions as consolidation. Responders patients [complete remission (CR) + unconfirmed CR + partial remission (PR)] were randomized to brief rituximab maintenance (Arm A), once every 2 months for a total of 4 doses, or observation (Arm B). MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to Euro-MRD consortium, using qualitative and quantitative PCR. Results: a total of 234 patients began chemoimmunotherapy: after induction and consolidation treatment overall response rate was 86%, with 69% CR. Of these, 210 completed the planned treatment and 202 responders were randomized. Up to date, median follow-up were 96 months from enrollment and 87 months from randomization; additional follow-up data were available for 127/146 (87%) not relapsed/progressed patients. Five- and 7-year PFS for the whole population were 57% and 51%, respectively; 5- and 7-year OS for the whole population were 85% and 80%, respectively. From enrollment, an advantage in term of PFS and also OS was observed in FLIPI low risk patients: 7-year PFS was 67% for low risk versus 38% for intermediate-high risk patients (p

Description: Bendamustine was introduced in Italy from 2008 and it was used as salvage therapy in patients pretreated, particularly in indolent lymphomas. Before approval as first-line treatment by the National Health System, starting from 2011 and thanks to our regional regulation, was possible to use Bendamustine in first line therapy as ‘off-label’ drug. The aim of this study was to collect all consecutive patients treated in first line with Bendamustine in 7 Tuscany centers. From June 2011 to December 2012, 72 patients were prospectively included in the study. Diagnosis was: Lymphocytic lymphoma in 25 patients (34%), Follicular lymphoma in 18 (25%), Diffuse large B cell lymphoma in 11 (15%), Mantle cell lymphoma in 10 (14%), Lymphoplasmocytic lymphoma in 5 (7%) and MALT in 3 (5%). Thirty-nine patients were treated with Bendamustine 90 mg/m2 for two days, 28 with 70 mg/m2 and 5 with 120 mg/m2. The analyzed population must be considered negatively selected as such was not proposed the standard therapy. Moreover the data coming from literature and the experience in pre-treated patients increased the interest of clinicians for this drug. In 14 patients Bendamustine was used alone, in 56 in combination with Rituximab or other drug. The overall median age was 69 years (range 45-89), in DLBCL was 81 years and 78 years in MCL. Considering the advanced age of this population we applied the geriatric score assessment and 25% of patients were unfit or frail. The median number of cycles performed was 4 (range 2 - 6). All patients but 2 were evaluable for response, 35 obtained a complete remission, 27 a partial remission considering the intention to treat the overall response rate was 86%, stable disease in 2 patients, progressive disease in 6 patients and not evaluable in 2 patients. According to histotype to note that all but two indolent lymphoma obtained a response; in aggressive lymphomas 4/11 DLBCL and 5/9 MCL reached a complete remission but 4 DLBCL and 2 MCL experienced rapid progression of the disease. Treatment was well tolerated, we observed: grade 3-4 neutropenia in 18 patients, no grade 3-4 anemia or thrombocytopenia. According to extrahematological toxicity was reported only grade 3-4 infection in 3 patients no other grade 3-4 toxicities were reported. Skin rush grade 1 was reported in in 5 patients. No toxic deaths were observed. After a median follow-up of 18 months the overall survival was 83%; 10 patients died all due to progressive disease. Progression free survival, after a median observation period of 12 months, was 60%; sixty-two patients are alive, 31 in continuous complete remission, 3 relapsed and 28 with disease under control. In conclusion in this ‘real life’ negatively selected population, the use of Bendamustine showed a very high response rate particularly in indolent lymphomas, promising results, also, are observed in aggressive lymphoma suggesting that this drug can be used with interesting result in elderly patients who can not receive the standard therapy. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2819 Background. Whilst positron emission tomography has a clear role in the evaluation of the final response to therapy in DLBCL, its predictive value at an interim time-point in this setting is controversial. Criteria of interpretation of Interim PET are yet to be standardized and the visual analysis of PET results by dichotomous evaluation is difficult to apply. Aim of the study was to determine the predictive value of interim (I-PET) and final PET (F-PET) on Progression Free Survival (PFS) in a cohort of DLBCL patients treated with R-CHOP. Patients and Methods. From April 2004 to October 2009, 88 DLBCL patients at diagnosis, at five Hematology Departments were included. All patients were treated with standard chemo-immunotherapy R-CHOP for 6 or 8 courses; therapy was performed as planned and never modified by I-PET results. Thirty-one patients received R-CHOP21, 57 R-CHOP14. Involved Field radiotherapy (IF-RT) for areas of bulky disease was delivered to 14 patients regardless of PET results. G-CSF was given to 21/31 R-CHOP21 patients and in all 57 R-CHOP14. PET scan was performed in all patients at diagnosis, during and at the end of therapy: all results were centrally reviewed and defined as positive or negative by visual dichotomous response criteria according to the First Consensus Conference (Deauville 2009). PFS and overall survival (OS) were analyzed by the Cox proportional hazards model, comparing the two arms by the Wald test with 95% CI. Due to small number of events, the Cox proportional hazards model was used in two independent bivariate analyses to assess the effect of different prognostic factors on PFS. Results. Clinical features were: median age 55 years (18-80); males/females 41/47; stages I-II/III-IV 29/59; Low/Low Intermediate International Prognostic Index score (IPI 0–2) 53 and Intermediate/Intermediate High/High IPI score (IPI 3–5) 35. I-PET was performed after two R-CHOP in 58 patients, after 3 or 4 in 30. At the end of therapy, 79 patients (90%) achieved a complete response (CR) and nine (10%) were non responders. Sixty-three patients (72%) were negative and 25 (28%) positive at I-PET; 77 patients (88%) were negative and 11 (12%) positive at F-PET; 15/25 (60%) I-PET positive patients converted at F-PET, while only 1/63 (2%) I-PET negative case had a positive F-PET (Table 1). The concordance between clinical CR and F-PET negativity was 97%: two patients, whilst in CR, had false positive final scans due to parotid and colorectal carcinoma (histologically confirmed) respectively. We evaluated the prognostic impact of PET results on the outcome. With a median follow-up of 26.2 months, 2-year OS and 2-year PFS were 91% and 77% respectively. There was a weak correlation between PFS and I-PET results: rates were 85% in negative and 72% in positive patients (p.05) (Figure 1A). Conversely F-PET strongly predicted PFS (p

Description: Abstract 99 Introduction. The PET scan has a definite role to assess the response at the end of treatment of DLBCL. The evaluation of response by PET after few courses of chemotherapy might be useful to predict chemosensitivity and possibly the outcome in this subset of patients. So far, the predictive value of interim PET in DLBCL pts is still contradictory. The visual analysis of PET results by dichotomous evaluation as positive or negative is often difficult to apply and standardized criteria of interpretation of interim PET have not been established yet. Moreover, published data are often based on retrospective studies, including miscellanea of subtypes and therapies. Our study was aimed to determine the predictive value of interim and final PET on PSF in DLBCL patients. Patients and Methods. From April 2004 to December 2008, 82 newly diagnosed DLBCL patients treated in 5 Hematology Department were included. Clinical features were as follows: median age 56 years (range 19-81); 42 males and 40 females, 29 patients stage I-II and 53 stage III-IV; according to IPI score 47 at low/low-intermediate risk and 35 at intermediate/intermediate-high. All patients were treated according to planned therapy, not modified by PET-2 results, with 6-8 R-CHOP. All patients had PET scan performed at the diagnosis, during treatment (PET-2) and at the end of therapy (PET-3). All PET results were defined as positive or negative by visual dichotomous consensus response criteria. Results. All patients were evaluable for response. PET-2 was performed after 2 R-CHOP in 46 pts, after 3 in 13 and after 4 in 23. At the end of therapy 73 pts (89%) achieved a CR and 9 (11%) were non responders. Fifty-five patients (67%) were negative and 27 (33%) positive at the PET-2 and 69 pts (84%) were negative and 13 (16%) positive at the PET-3. The concordance between clinical CR and PET-3 negativity was 99%: one CR pt was false PET-3 positive due to parothid carcinoma . Correlation between PET results and outcome was evaluated. There was correlation between PET-2 results and CR rate: CR 96% in PET-2 negative pts vs 74% in PET-2 positive (p .004). With a median FU of 18 months, PFS was 78%. PET-2 did not correlate with PFS (p .198): 46/55 (84%) PET-2 negative patients were in CCR and 20/27 (74%) PET-2 positive patients did not progres (Figure 1A). Conversely PET-3 strongly predicted PFS (p .015): 58/69 (84%) were in CCR and 8/13 (61%) did not progressed. (Figure 1B). A further analysis for progression event was performed to adjust the effect of PET-2 analysis for other known risk factors (age up to/over 60, stage, Performance status, LDH, number of extranodal sites, IPI, bulky, Bone Marrow involvement): only LDH (p .005)and IPI 0-2 vs 3-5 (p .001 ) were confirmed as independent predictors of progression event. Conclusions. Our results indicate that in this omogeneous group of DLBCL patients treated with R-CHOP interim PET failed to predict outcome. However, a longer follow up is necessary to validate our data. Conversely PET results at the end of treatment strongly correlate with PFS. Prospective larger studies will be needed to establish the real role of interim PET to predict the outcome in this subset of patients. Disclosures: Ladetto: CELGENE: Honoraria; JANSSEN-CILAG: Research Funding. Vitolo:Roche: lecture fees.

Description: Abstract 4995 Background The response evaluation is performed by computed tomography (CT) as a standard tool in DLBCL. The introduction the FDG-PET performed for post treatment response assessment of aggressive Non Hodgkin's Lymphoma (NHL) is advised by the Revised International Workshop Criteria (IWC). We explored the predictive value by FDG-PET scan performed at the end of therapy in patients (pts) with DLBCL treated with rituximab-containing regimens . Patients From 2003 at 2008 were included 86 pts with DLBCL treated with Rituximab and CHOP or CHOP-like regimens. The FDG-PET and CT was mandatory at baseline and at the end of therapy to include pts in the study. We evaluated the progression free survival (PFS) of pts starting from the time of diagnosis to early relapse or disease progression or last follow-up. Results Median age was 60 years (28-78), 40 pts were female and 46 male, 38 pts presented stage I-II and 48 stage III-IV. The International Prognostic Index (IPI) was low in 20% of pts, low-intermediate in 50%, intermediate-high in 28% and high risk in 2%; bulky was reported in 24 pts. Seventy-seven pts attained complete remission (CR) (89%), 8 pts (9%) partial remission (PR) and 1 pts progression disease (2%). The FDG-PET and CT performed at the end of therapy were both negative in 61 pts (71%); both positive in 9 pts (10%). In the remaining pts the FDG-PET and CT scan performed post therapy were discordant in particular in 13 pts (15%) FDG-PET was negative and CT was positive and in 3 pts (4%) FDG-PET was positive and CT was negative. Thus the positive predictive value of a FDG-PET at the end of therapy was 63% and the negative predictive value was 87%. The sensitivity and specificity of FDG-PET at the end of therapy were 41% and 94% respectively. The positive predictive value and the negative predictive value of a CT at the end of therapy were 43% and 87% respectively. The sensitivity of CT at the end of therapy was 53% and the specificity was 83%. Fifthteen out seventy-four patients (20%) with negative FDG-PET progress or relapse within 6 months (median 4 months). Five out twenty (25%) FDG-PET negative bulky disease pts progress or relapse within 6 months moreover four out seventeen (24%) CT negative bulky disease pts progress or relapse. With a median follow-up of 20 months (range 7-83) the overall survival was 86%, and with a median follow-up of 15 months (range 2-78) the PFS was 76%. Conclusions FDG-PET shows an high specificity but a very low sensibility in DLBCL. An high rate of false negative FDG-PET was observed in bulky disease patients. We have observed that pts with negative FDG-PET presented a rapid relapse or progression therefore we can consider that probably in non-Hodgkin's lymphoma PET should be performed after four months from the end of therapy to reduce false negative. Obviously larger study are needed but at the moment CT remain the most sensible instrument to define CR in non-Hodgkin's lymphoma. Disclosures Vitolo: Roche:.

Description: Abstract 1784 Introduction. The outcome of MCL is unfavourable, with continuous relapses. The MIPI, a clinical score, defined performance status, age, LDH and leucocyte counts as predictors of MCL outcome. Ki-67 as cell proliferation index was evaluated in biological-MIPI (MIPI-b). Aim of the study was to tested MIPI on a retrospective group of MCL patients treated with Rituximab-chemotherapy with or without High Dose Chemotherapy and autologous stem cell transplantation (R-HDC); secondary endpoints were: to evaluate the feasibility of MIPI-b on a retrospective population and to quantify the predictive discrimination of IPI, MIPI, MIPI-b on the outcome of MCL in the Rituximab era. Methods. Between 1999 and 2009, 206 MCL 〉18 years at diagnosis consecutively treated in seven Italian institutions were included into the study. Histology was centrally reviewed and, if possible, Ki-67 evaluation was performed. Overall survival (OS) and failure-free survival (FFS) curves were estimated both overall and stratified by MIPI, MIPI-b and IPI score. Differences between curves were tested using the 2-tailed log-rank test. In order to quantify the predictive discrimination of MIPI, MIPI-b and IPI scores, a Cox's model analysis and univariate logistic models (with death and failure event as binary outcomes) were fitted and the area under the receiver operating characteristic (ROC) curves (c-index) was estimated in a subgroup of 120 patients that fulfilled MIPI, MIPI-b and IPI scores. Results. Clinical characteristics were: median age 61 (34-85) years, 78% stage IV, 73% with bone marrow involvement, 16% with blastoid variant; median leucocyte counts at diagnosis was 7.53×103 (2.38-175). First-line treatments were: R-HDC in 51%, Rituximab-Fludarabine based chemotherapy in 12%, Rituximab-CHOP in 32% and other Rituximab containing regimens in 5%. Ki-67 evaluation was performed in 135 patients; median Ki-67 value was 30%. Patients at high-risk (HR) were 29% according to MIPI, 18% according to MIPI-b and 33% to IPI. With a median follow-up of 48 months, 4-year OS was 72% (95% CI:65-78) and 4-year FFS was 49% (95%CI: 41–56). Four-year OS according to MIPI by risk groups was: LR 94% (95%CI: 85–97), IR 66% (95%CI: 47–80), HR 41% (95%CI: 26–55) and according to IPI: LR 87% (95%CI: 73–94), IR 88% (95%CI: 74–95), HR 41% (95%CI: 26–55) (Figure 1). In the subgroup of 120 patients that fulfilled MIPI, MIPI-b and IP scores an univariate logistic model and a Cox's model analysis were fitted. The c-index and Cox-index for death event were 76% and 75% for MIPI, 69% and 69% for MIPIb, 76% and 71% for IPI respectively; the c-index and Cox-index for failure event were 61% and 68% for MIPI, 59% and 64% for MIPIb, 68% and 66% for IPI respectively. A sub-analysis was conducted to validate the role of MIPI in R-HDC group; an univariate logistic model and a Cox's model analysis were fitted and the c-index and Cox-index for death event and for failure event were calculated (Table 1). Conclusions. MIPI score was confirmed as a good predictor of death event in MCL retrospective patients treated with Rituximab-chemotherapy regimens. MIPI score should be a good predictor of death event also in patients treated with R-HDC. The impact of MIPI-b score should be tested in prospective trials, with central histology review. New therapeutic strategies are warranted to improve the outcome of MCL namely in MIPI-HR group. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3685 Background: Ocular adnexal lymphomas (OALs) represents 8% of primary extranodal lymphomas, 80% of OALs constitutes extranodal marginal zone lymphomas (EMZL). In the last years the incidence of OLAs has increased more rapidly than Non Hodgkin Lymphoma at other extranodal site. Radiotherapy is associated to high rates of local disease control, but also to the risk of relapse and immediate and delayed complications, such as xerophtalmy, corneal ulcerations, cataract and retinal damage. Surgery is a feasible option, but not always satisfactory in terms of disease control. Single-agent chemotherapy with alkylating agents is used for the treatment of low-grade lymphomas, including OALs. Rituximab, a chimeric anti-CD20 monoclonal antibody, is effective in EMZL and in OALs. Aims: We investigated the efficacy and the safety of a combination of chlorambucil and rituximab as first line treatment in patients with OALs. Methods: Patients with histologically proven low-grade OALs were enrolled in this study. Staging included CT-scan of the orbit, neck, chest and abdomen, MR of the orbit, Chlamydia psittaci (Cp) detected by PCR and bone marrow biopsy. Treatment consisted of chlorambucil (0,1 mg/Kg/die for 45 days, then on days 1 to 15 monthly for 4 months) and rituximab (375 mg/sqm weekly for 4 doses, then monthly for 4 infusions). Toxicities were reported according to WHO criteria. At the end of treatment patients were restaged clinically and with a MR of the orbit. Results: Since November 2003 to November 2010 twenty consecutive, histologically proven, low-grade OALs (19 EMZL, a grade I follicular lymphoma) have been treated according to protocol. The median interval between onset of the first symptoms and diagnosis was 13 months (range, 4 months – 3 years). Twelve pts were female (60%) and eight pts were male (40%). Median age at diagnosis was 68 years (range, 35–86 years). Disease was localized in the conjunctiva in 15 patients (75%), in the lacrimal glands in 2 patients (10%) and in other orbital sites in the last three patients (15%). Nineteen patients presented a stage I disease, one stage IV, and no patient showed B-symptoms. LDH was within normal range in 17 of 20 patients (85%), ECOG-PS was 0 and International prognostic Index (IPI) was low or low-intermediate in all patients. We evaluated PCR for Chlamydia psittaci in the first ten consecutive pts and it was negative. All patients completed the treatment without delay; there was no grade III-IV toxicities neither hospitalizations. Five patients had grade 1–2 rituximab infusion-related reactions usually during the first infusion and haematological toxicity was mild. At the end of treatment 19 patients (95%) resulted in CR, and one obtained a partial remission (5%). After a median follow-up of 56 months (range, 21–106 months) all patients are alive, 17 maintained CR and two relapsed (after 3 and 5 years), one was retreated with the same protocol and attained a new CR and the other relapsed systemically as follicular lymphoma. The patient in PR after first line obtained CR with second line therapy (rituximab fludarabine and cyclophosphamide). The median PFS was 43 months (range, 3–98 months). All patients performed ophthalmologic follow-up visits: we did not report ocular toxicities, and all patients conserved a normal visual function, including acuity. No secondary myelodisplatic syndrome or secondary neoplasms are reported. Conclusions: After a long follow-up the combination of rituximab and chlorambucil proved to be low toxic, feasible and effective therapy for primary OALs. No delayed ocular or haematological complications are reported. For this reason the combination of immunotherapy and mild chemotherapy should be considered for the treatment of this indolent lymphoma. Disclosures: No relevant conflicts of interest to declare.