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Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P = .0475); F-PET 83% versus 64% (P < .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio [HR] = 5.03, P = .015 vs 1.27, P = 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P = .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.

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.

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 Conclusions. Our results indicate that in DLBCL patients treated with first-line R-CHOP, a positive I-PET does not predict a worse outcome: indeed the majority of I-PET positive patients achieved CR at the end of therapy. Conversely, F-PET results strongly correlate with PFS. Larger prospective studies and standardization of criteria for interim PET evaluation are needed to better assess the prognostic value of interim PET in DLBCL patients. Disclosures: No relevant conflicts of interest to declare.

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.

Abstract 2928 Poster Board II-904 Introduction: A new prognostic clinical index (MIPI) and a biological one with cell proliferation (Ki-67) evaluation (MIPIb), were defined specifically for MCL to give a more reliable estimation of outcome (Hoster 2008). Aim of our analysis was to test MIPI and MIPIb on a retrospective series of MCL patients treated with R-chemotherapy. Patients and methods: Between 1999 and 2008, 136 MCL at diagnosis consecutively treated in five institutions entered into the study. Histology was centrally reviewed. Clinical characteristics were: median age 62 (37-84) years, 78% stage IV, 73% with bone marrow involvement and 15% with blastoid variant. First-line treatments were: R-high-dose chemotherapy with Autologous Stem Cell Transplantation (R-HDC) in 48 patients, R-Fludarabine based chemotherapy in 22, R-CHOP-like in 50 and other R containing regimens in 16. Ki-67 evaluation was performed in 93 patients; 43 were not, due to inadequate pathological materials. Overall Survival (OS) and failure-free survival (FFS) curves were estimated both overall and stratified by MIPI, MIPIb and IPI score. Differences between curves were tested using the 2-tailed log-rank test. In order to quantify the predictive discrimination of MIPI, MIPIb and IPI scores, in a subgroup of 84 patients fulfilled MIPI, MIPIb 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. Results: Prognostic index stratification was as follows: according to MIPI 45 patients (33%) were at low-risk (LR, 0-3), 36 (26%) at intermediate-risk (IR, 4-5), 43 (32%) at high-risk (HR, >5) and 12 missing; according to MIPIb 70 patients (51%) were at LR (0-5.699), 7 (5%) at IR (5.7-6.499), 16 (12%) at HR (>6.5) and 43 missing; according to IPI 38 patients (28%) were at LR, 41 (30%) at LIR, 47 (35%) at IH-HR and 10 missing. Responses were as follows: complete 74, partial 29, no response 22, not yet evaluable 11. With a median follow-up of 28 months, 2-year OS was 80% (95% CI:71%-86%) and 2-year FFS was 60% (95%CI: 51%-69%). 2-year OS and 2-year FFS rates according to MIPI, MIPIb and IPI were shown in table 1. Eighty-four patients had all the factors to accurately calculate MIPI, MIPIb and IPI; in this subgroup, an univariate logistic model and a Cox's model including the time at the event were performed. The c-index and Cox-index for death event were 73% and 77% for MIPI, 72% and 73% for MIPIb, 67% and 65% for IPI respectively; the c-index and Cox-index for failure event were 66% and 72% for MIPI, 66% and 65% for MIPIb, 67% and 64% for IPI respectively. A further analysis for death event was performed to adjust the effect of MIPI for other known risk factors (Ann-Arbor stage, Bone Marrow involvement, blastoid variant, number of extranodal sites). In a Cox model, MIPI score and number of extranodal sites were confirmed as independent predictors of death event: adjusted hazard ratio was 8.75 (95%CI: 3.14-24.4, p= Discussion: MIPI score was confirmed as a strong predictor of death event in MCL retrospective patients treated with R-chemotherapy regimens. New therapeutic strategies are warranted to improve the outcome of MCL namely in MIPI-HR group. Disclosures: Ladetto: CELGENE: Honoraria; JANSSEN-CILAG: Research Funding. Vitolo:Roche:.