ALBERT

Description: Abstract 2462 Background: Two of the largest trials ever conducted in patients with chronic lymphocytic leukemia (CLL) have shown that the addition of rituximab to fludarabine plus cyclophosphamide (R-FC) significantly improves outcome. However, myelotoxicity and immunosuppression limit the use of this regimen in patients with impaired performance status and pre-existing co-morbidities, predominantly in the elderly. Chlorambucil (CLB) remains a first-line treatment option for such patients. The use of CLB in combination with R is thus an attractive therapeutic option in view of the potentially increased activity compared to CLB alone and the likely good tolerability. This study was designed to determine whether the R-CLB combination is feasible and beneficial as first-line treatment for elderly patients with CLL and to define the role of maintenance R. Patients and Methods: Between October 2008 and January 2010, 97 elderly patients with untreated CD20+ CLL requiring therapy according to the IWCLL criteria were enrolled into the protocol. CLB treatment was administered every 28 days for up to 8 courses at a dose of 8 mg/m2/day p.o. on days 1–7 combined with 375 mg/m2 R for cycle 3 and 500 mg/m2 for cycles 4–8. Responsive patients were randomized to R maintenance (375 mg/m2 every 2 months for 2 years) versus observation. At baseline, blood samples were taken for FISH analysis, IgVH mutational status and expression of Zap-70 and CD38. Minimal residual disease (MRD) was planned to be evaluated on peripheral blood (PB) and bone marrow (BM) cells by four-color flow cytometry and, when required, by PCR. The primary endpoint was the overall response rate at the end of the induction phase defined according to the IWCLL 2008 on the intention-to-treat (ITT) population (all enrolled patients who received at least 1 dose of R). Secondary endpoints included the adverse event (AE) profile, progression-free and overall survival. Results: These are the data of the planned interim analysis based on the first 54 evaluable patients from 19 Italian centers, including tumor response at the end of the induction phase and safety. The median age of patients was 70.5 years (range 61–84): 14.8% were between 61 and 64, 31.5% between 65 and 69, 31.5% between 70 and 74, 16.7% between 75 and 79, and 5.6% were ≥80 years; thus, 53.8% of patients were over the age of 70; 70.4% were males; 25.9% were Binet stage A, 57.4% stage B and 16.7% stage C. The overall incidences of trisomy 12 and abnormalities of 13q, 11q23 and 17p13 were 24.5%, 52.8%, 20.8% and 5.7%, respectively; 7.5% of patients had p53 mutations. Of the 51/54 patients analyzed for the IgVH mutational status, 64.7% were unmutated; of the 53/54 patients studied, 39.6% were CD38+ and 71.7% were Zap-70+. The overall response rate on an ITT analysis was 81.4% (44/54 patients); a CR assessed by CT scan and trephine immunohistochemistry was found in 16.7% of cases (9 patients: 4 in Binet stage A, 3 in stage B and 2 in stage C), a CRi in 3.7% (2 patients), a nPR in 1.9% (1 patient) and a PR in 59.3% (32 patients). Eight of the 9 CR cases were investigated for MRD by flow cytometry and all proved positive: 6/8 had MRD levels

Description: Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

Description: Abstract 787 Background: Many studies support the value of PCR-based MRD detection using the bcl-2-IgH translocation as an outcome predictor in FL but some failed to confirm this observation. Concerns have been raised particularly for programs which are highly Rituximab (Rtx) intensive (with or without maintenance) and non-ASCT-based. The ML17638 study, contained an extensive centralized MRD monitoring program, whose results are here presented. Patients and methods: Clinical results of study have been already reported (Vitolo et al, ASH 2011). The program consisted of 4 R-FND courses (Rtx, fludarabine, mitoxantrone, dexamethasone) followed by 4 doses of weekly Rtx. Patients (pts) achieving 3partial response (PR) were randomized to Rtx maintenance (arm A) or observation (arm B). A total of 234 untreated elderly (age 60–75 years) pts at diagnosis were enrolled. With a median follow-up from randomization of 34 months, 3-year PFS and OS were 66% (95%CI:59-72%) and 89% (95%CI:85-93%), with a clear trend in favor of arm A for 2-year PFS (81% vs 69%). At enrolment, pts were screened for a molecular marker based on the bcl-2/IgH MBR or mcr. If found, pts were tested at 8 fixed timepoints: at month 5 (M5) after 4-R-FND, at the end of induction therapy (M8) and during maintenance/observation and follow-up (M12,M18,M24,M30,M36 and M42) or until relapse. MRD was assessed by both nested PCR (n-PCR) and real time quantitative PCR (RQ-PCR) on BM cells. Methods have been already reported (Ladetto Exp Hematol 2001). RQ-PCR was performed and analyzed according to the Euro-MRD guidelines (Van der Velden Leukemia 2007). The lab performs routine quality controls in the context of Euro-MRD and was blinded to clinical results and radomization arm. The impact of MRD on PFS was evaluated by log-rank tests and Cox models including age, sex, FLIPI, ECOG PS and complete remission (CR). In addition, the effect of PCR negativity on PFS during the whole follow-up period was evaluated by a time-varying covariate included in the models, also considered in a cumulative way (0, 1, 2, 3 or more consecutive PCR-negative timepoints). Results: 229 of 234 enrolled pts (98%) were screened at study entry. A molecular marker was found in 118 (51.5%). Of these, 9 were excluded due to withdrawal before M5 (7) or inadequate sampling (2). Overall, 800 follow-up samples were expected. Of these, 707 (88%) were received and analysed: 98% of pts were evaluable for 350% of timepoints and 87% for 375%. Pts with and without a marker had identical PFS (61% at 42m for both). Sixty six per cent of pts achieved PCR-negativity after R-FND and 81% at the end of treatment, with a mean tumor burden reduction of 11 natural logaritm after R-FND and a further decrease of 1.6 after the 4 weekly Rtx. At randomization, PCR-positivity rate was similar in the two arms while during and after maintenance pts in Arm A had a lower rate of PCR-positivity (9% vs 17% p=0.02). The achievement of PCR-negativity by both n-PCR and RQ-PCR at timepoints M8,12,18 and 24 predicted a better PFS (M5 not predictive, M30, 36, 42 have too early follow up for meaningful evaluation). After M8, 2-year PFS was significantly better in PCR-negative than PCR-positive pts: 72% vs 39% (p=0.007, Fig. 1). Achieving a double PCR-negativity at M8-M12 or triple molecular negativity at M8-M12-M18 was associated with a further increase of PFS (82% vs 46% for months 8–12, p=0.001 and 87% vs 53% for months 8–12-18, p=0.001). PCR-negativity at M8 ensured a subsequent better PFS both in CR (p=0.023, HR=0.33, 95%CI: 0.13–0.86) and PR (p=0.074, HR=0.28, 95%CI: 0.07–1.13) pts (Fig. 2). Disclosures: Ladetto: Hoffman-La Roche: Consultancy, Honoraria. Rossi:Roche: Honoraria. Musto:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gamba:Roche: Employment. Vitolo:Celgene: Honoraria; Janssin-Cilag: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees.

Description: Fludarabine in combination with cyclophosphamide (FC) plus rituximab (R) is an effective treatment for newly diagnosed as well as relapsed low-grade non-Hodgin’s lymphoma (NHL), including chronic lymphocytic leukemia (TAM 2006 and 2008, Keating 2005, Sacchi 2007). Maintenance treatment with R improves overall and progression-free survival in patients both with and without rituximab during induction, with relapsed/resistant follicular NHL (Van Oers 2006). We investigated efficacy and safety of the chemo-immunotherapy FCR followed by rituximab maintenance treatment in patients with advanced untreated indolent B-cell non follicular lymphomas (INFL). Patients and methods: from July 2005 to May 2007, 47 pts whit untreated advanced stage INFL (23 lymphocytic, 20 limphoplasmacytic and 4 nodal marginal zone NHL) were enrolled in an open label, single arm, multicenter phase II study, consisting with 6 courses of FC (Fludarabine, 25 mg/m2 i.v. plus Cyclophosphamide, 250 mg/m2, days 2–4) plus 8 doses of R (375 mg/m2, day 1 every FC cycle and day 14 of cycles 4 and 5) followed by R maintenance (375 mg/m2 every two months for 4 doses). Prophylactic antibiotic treatment with cotrimoxazole (two tablets three times a week) and antifungal profilaxis with itraconazole was planned from the beginning of chemotherapy to three months later or until normalization of CD4 count. The primary endpoint of this study is the percentage of failure free patients after two years from the treatment start. Results: 46/47 pts were evaluable for therapeutic response: median age 59 years (31–68), M/F ratio 28/18; stage III/ IV 44; B symptoms and splenomegaly 11 and 14 pts respectively; FLIPI scores were: 0–1, 16 pts (34.8%), score 2, 19 pts (41.3%) and score ≥ 3, 11 pts (23.9%). Forty-five patients received all the 6 courses of treatment and 1 patient 3 courses only. The ORR was 96% (44/46 pts) with 28 complete (61%) and 16 (35%) partial responses; 2 pts were in MR/SD. A total of 274 courses of FRC were given to 47 patients. The most frequent serious toxicity (NCI-CTC grade 3–4) was neutropenia that was reported in 55% of the courses. Three cases of Herpes zoster infection were reported. All the patients are still alive. Conclusions: in a series of INFL at diagnosis, FCR regimen is safe and effective with a very high CR rate. The whole study will provide insights on the role of R maintenance after R-chemotherapy in a particular subset of low-grade NHLs.

Description: Abstract 294 Rituximab plus fludarabine/cyclophosphamide (R-FC) is currently the standard of care for fit patients with untreated or relapsed CLL. However, patients with CLL are predominantly an elderly population and many of these patients may have comorbidities that make them less suitable to receive fludarabine-containing therapy. Chlorambucil-based treatments are frequently used for these patients despite the fact that clinical benefits are limited. There is a need for well-tolerated and more efficacious treatment regimens for these patients. The ML21445 study evaluated the combination of rituximab and chlorambucil (R-chlorambucil) as first-line treatment for patients with CLL considered ineligible for treatment with the current standard of care, R-FC. Patients aged 〉65 years (or 60–65 years and ineligible for fludarabine) were treated with eight 28-day cycles of chlorambucil (8 mg/m2/day Days 1–7) with rituximab administered on Day 1 of cycle 3 (375 mg/m2) and cycles 4–8 (500 mg/m2). Patients with a response at the end of induction were randomized to rituximab maintenance therapy (375 mg/m2 every 8 weeks for 2 years) or observation. The induction phase of the study is complete while the maintenance phase is still ongoing. The overall response rate (ORR) in 85 patients who received at least one dose of rituximab during induction was 81.2% (n = 69) with 16.5% (n = 14) achieving a complete response (CR) and 2.4% (n = 2) a CR with incomplete bone marrow recovery (CRi). ORR and CR rates were similar across the different Binet stages (ORR: Binet A 86.4%, Binet B 79.6%, Binet C 78.6%) and age categories (ORR: 60–64 years 84.6%, 65–69 years 85.2%, 70–74 years 75.0%, ≥75 years 81.0%). Two of four patients aged ≥80 years responded to induction treatment. Logistic regression analysis revealed no correlation between known biological prognostic factors – CD38, cytogenetics, IGHV mutational status, ZAP-70, thymidine kinase, soluble CD23, and beta-2 microglobulin – and response to treatment. To further investigate possible factors influencing response, pre-treatment patterns of gene expression were analyzed in different patient subgroups. Material was available for 62 patients, including 16 with CR/CRi, 41 partial responders and 5 non-responders. In an exploratory analysis, mRNA expression was examined using Affymetrix® Human Genome U133 microarrays. This revealed marked differences in pre-treatment gene expression profiles between response groups. Non-responders showed a homogeneous gene expression signature involving up-modulation of transcripts involved in anti-apoptotic and pro-proliferative pathways, including K-ras and N-ras. CR/CRi patients also showed a homogeneous pattern of gene expression that was clearly distinct from non-responding patients, while patients with a partial response showed a more heterogeneous pattern of gene expression before treatment. These initial findings reflect the heterogeneity of CLL and suggest that microarray analysis of gene expression may be useful in predicting response to R-chlorambucil in elderly patients with CLL. Disclosures: Foa: Roche: Consultancy, Speakers Bureau. Cuneo:Roche: Consultancy, Speakers Bureau. Montillo:Roche: Membership on an entity's Board of Directors or advisory committees. Alietti:Roche: Employment. Runggaldier:Roche: Employment. Gamba:Roche Italia: Employment.

Description: Abstract 1706 Poster Board I-732 Introduction in order to maintain efficacy and reduce toxicity of the treatment in elderly follicular lymphoma (FL) patients, we designed a study with a short chemo-immunotherapy R-FND with Rituximab consolidation followed by randomization between R maintenance or observation. Material and methods: From January 2004 to December 2007, 242 patients (age 60-75) with untreated advanced stage FL were enrolled by 33 IIL centres. Treatment plan was: 4 courses of R-FND (standard doses of Rituximab, Fludarabine, Mitoxantrone, Dexamethasone) every 28 days followed by 4 weekly Rituximab infusions as consolidation; responding (CR+CRu+PR) patients were randomized between Rituximab maintenance, one dose every 2 months for a total of 4 doses or observation. Qualitative and quantitative PCR monitoring for IgH/Bcl-2 rearrangement on bone marrow (BM) was performed at diagnosis, after R-FND and R consolidation and during maintenance/observation. Results 234 patients were eligible for the study: median age was 66 yrs; advanced stage II 14%, stage III 21% and stage IV 65%; BM involvement and B symptoms were documented in 55% and 18% respectively. FLIPI score was: Low 11%, Intermediate 34%, High 55%. One and 2 or more comorbidities were present in 36% and 23% of the patients respectively. Qualitative PCR analysis for IgH/Bcl-2 was performed in 223 patients at diagnosis and 51% were positive. Two hundred and two (86%) patients completed the induction treatment and were randomized between maintenance or observation; 32 were not because of: stable/progressive disease (16), adverse events (10) or other causes (6). Overall response at the end of treatment was 86% with 69% CR and 18% PR; PCR negativity at the end of treatment was 75%. Rituximab consolidation was able to induce CR in 37/90 (41%) partial responders and to increase PCR negativity from 61% to 75%. With a median follow-up of 22 months, two-years OS and PFS were 92% (95% CI 87%-95%) and 75% (95% CI 68%-81%), respectively (see Figure). Two-years PFS rates according to FLIPI score were 85% for low/intermediate risk and 65% for high risk (p 〈 0.001); 2-years PFS rates were 57% and 79% respectively in patients with and without B symptoms (p 〈 0.001). The patients in more advanced decade (〉 70 years) or those with 2 or more comorbidities did as well as younger ones or those with one or no comorbidities: 2-yr PFS rates for patients more or less seventy were 73% vs 76% (p = 0.39); for patients with ≥2 comorbidities or one or none were 84% vs 67% vs 76%, respectively (p = 0.82). A total of 1119 courses were delivered; the most frequent CTC grade 3-4 toxicity was neutropenia in 25% of the courses, with only 13 serious infections. One patients developed acute myelogenous leukaemia during treatment and died. Two toxic deaths during treatment (0.8%) occurred: 1 HBV reactivation and 1 Steven Johnson syndrome. So far 212 patients are alive; besides the above mentioned deaths, 15 patients died of lymphoma, 2 died of cardiac failure, 1 died of stroke and 1 died of drowning. So far too few events occurred to proper analyse the efficacy of the Rituximab maintenance. In the maintenance/observation phase the following severe (WHO grade 3-4) toxicities were recorded: 15 patients experienced neutropenia, seven cardiac events, four infections; no other relevant toxicities were recorded. The cumulative incidences of toxic events accounting for competing events at 18 months for maintenance arm (Arm A) versus observation arm (Arm B) were as follows: neutropenia 17% vs 1% (p

Description: Abstract 2686 Poster Board II-662 Introduction: Fludarabine in combination with cyclophosphamide (FC) plus rituximab (R) is an effective treatment for newly diagnosed as well as relapsed low-grade non-Hodgin's lymphoma (NHL). The role of maintenance treatment with R has been demonstrated in relapsed/resistant follicular NHL improving overall and progression-free survival. We investigated efficacy and safety of the chemo-immunotherapy FCR followed by rituximab maintenance treatment in patients with advanced untreated indolent B-cell non follicular lymphomas (INFL). Patients and methods: from July 2005 to May 2007, 47 pts whit untreated advanced stage INFL (23 lymphocytic, 20 limphoplasmacytic and 4 nodal marginal zone NHL) were enrolled by 10 IIL centres, in an open label, single arm, multicenter phase II study. Treatment plan was: 6 courses of FC (Fludarabine, 25 mg/m2 i.v. plus Cyclophosphamide, 250 mg/m2, days 2–4) every 28 days plus 8 doses of R (375 mg/m2 , day 1 every FC cycle and day 14 of cycles 4 and 5) followed by R maintenance (375 mg/m2 every two months for 4 doses). Prophylactic antibiotic treatment with cotrimoxazole (two tablets three times a week) and antifungal profilaxis with itraconazole was planned from the beginning of chemotherapy to three months later or until normalization of CD4 count. The primary endpoint of this study is the percentage of failure free patients after two years from the treatment start. Results: all the patients were evaluable for safety analysis and 46/47 pts were evaluable in terms of intention to treat analysis. Median age was 59 years (31–68) and M/F ratio was 28/18; stages II/III/IV were 2/2/44; B symptoms and splenomegaly were observed in 11 and 14 pts respectively; FLIPI scores were: 0–1 in 16 pts (34.8%), score 2 in 19 pts (41.3%) and score ≥ 3 in 11 pts (23.9%). Forty-one patients (87.2%) completed the planned therapeutic program; the remaining 6 patients stopped the treatment for SAE (4 pts) or for other reasons (2 pts) after 9 courses (1 pt), 8 (1 pt), 6 (2 pts), 3 (1 pt) and 1 (1 pt). Overall response at the end of treatment was 80.4% with 60.9% CR and 19.5% PR. One patient relapsed during maintenance phase. All the patients are still alive. A total of 279 courses of FC were given to 47 patients. All the patients presented at least one toxic/adverse events (AE); 11 pts developed 12 serious AEs, but only 6 were related to therapy. Seventeen pts had to interrupt (4 pts), delay or reduce therapy. Three hundred twenty related AEs were registered: grade 1–2: 228 events; grade 3–4: 92 events. Among these last the most frequent was neutropenia: 30 pts presented 83 episodes whose grade 3–4 related to the therapy were 58. During maintenance phase, 4 episodes of neutropenia occurred (2 of grade 3–4). Sixteen pts presented 31 infective episodes; the most frequent were: 5 Herpes zoster infections, 5 pneumonia (1 mycotic) and 4 urinary tract infections. Conclusions: in a series of INFL at diagnosis, FCR regimen is effective with a very high CR rate. The toxicity was acceptable and the schedule can be considered safe although the frequence of neutropenia and infective events require a close surveillance. The next year of follow-up will allow us to establish the failure free survival after two years from the treatment start. Disclosures: Vitolo: Roche: Lecture fees. Morra:Roche: Lecture fees.

Description: Abstract 777 Introduction. Fludarabine containing regimens are effective in FL; the role of Rituximab (R) maintenance has been established recently. Aim of the study was to investigate efficacy and safety of R-maintenance vs. observation in elderly FL patients who respond to a brief chemo-immunotherapy with four courses of R-FND + four doses of Rituximab as consolidation. Methods. From January 2004 to December 2007, elderly patients (age 60–75) with untreated advanced stage FL who required treatment, were enrolled by 33 FIL centers. Treatment plan was: four courses of R-FND (standard doses of Rituximab, Fludarabine, Mitoxantrone, Dexamethasone) every 28 days followed by four weekly Rituximab infusions as consolidation; responding (Complete Response, CR + CRu + Partial Response, PR) patients were randomized between a short Rituximab maintenance with a single dose every two months for a total of four doses (Arm A) or observation (Arm B). Qualitative and quantitative PCR monitoring for IgH/Bcl-2 rearrangement on bone marrow (BM) was performed at diagnosis, after R-FND and R consolidation and during maintenance/observation. Results. 242 patients were enrolled at diagnosis in the study and 234 were eligible for treatment: median age was 66 yrs; advanced stage II 14%, stage III 21% and stage IV 65%; BM involvement and B symptoms were documented in 55% and 18% respectively. According to FLIPI risk patients were: Low 11%, Intermediate 34%, High 55%. According to Comprehensive Geriatric Assessment (CGA), concomitant illness were: one in 38% and greater than or equal to two in 23% of patients. Qualitative PCR analysis for IgH/Bcl-2, performed in 223 patients at diagnosis, was positive in 49%. Two hundred and two (86%) patients completed the induction treatment and were randomized between maintenance or observation; 32 were not because of stable/progressive disease (15), adverse events (nine) or other causes (eight). At the end of chemoimmunoterapy and consolidation overall response rate was 86% with 68% CR and 18% PR. After four courses of chemo-immunotherapy, 90 patients were in PR of whom 37 (41%) were converted to CR with the addition of Rituximab consolidation. As regard to Bcl2 analysis, PCR negativity was detected in 61% after R-FND and increased to 73% after R consolidation. With a median follow-up of 33 months, two-years Overall Survival and Progression Free Survival (PFS) were 93% (95% CI 92%–97%) and 77% (95% CI 71%–93%), respectively. Two-years PFS according to maintenance/observation phase was: 80% vs 68% (p.225), Figure 1. Two-years PFS rates according to FLIPI score were 87% for low/intermediate risk and 70% for high risk (p 〈 0.0001). A total of 1119 courses were delivered; the most frequent CTC grade 3–4 toxicity was neutropenia in 25% of the courses, with only 13 events of serious infections. Two toxic deaths during treatment (0.8%) occurred: 1 HBV reactivation and 1 Steven Johnson syndrome. In the maintenance/observation phase the following severe (WHO grade 3–4) toxicities were recorded: 15 patients experienced neutropenia, 8 cardiac events, 4 infections; no other relevant toxicities were recorded. Second malignancy were recorded in 11 patients. Conclusions. a short term chemo-immunotherapy R-FND + Rituximab consolidation is able to achieve high CR rate and a good two-years PFS in elderly FL patients. Good results were also observed in higk-risk FLIPI score. Two-years PFS of 80% in patients randomized to R maintenance was promising although there was no statistical difference compared to observation. This finding may be attributed to the relatively short follow-up or to the choice of a short course of Rituximab maintenance (only four doses) or both.Figure 1Figure 1. Disclosures: Vitolo: Jannsen-Cilag: Speakers Bureau; Celgene: Speakers Bureau; Roche Italy: Speakers Bureau. Off Label Use: The study includes use of Rituximab as maintenance in responding patients after first line chemoimmunotherapy. Gamba:Roche Italia: Employment. Supekar:Roche Italia: Employment.

Description: Key Points PCR negativity is a strong outcome predictor after rituximab-intensive immunochemotherapy at multiple posttreatment times. PCR is predictive even when maintenance is delivered, and accumulation of PCR-negative results further reduces the likelihood of relapse.

Description: Previous uncontrolled studies have highlighted the potential activity of Rituximab in patients with idiopathic thrombocytopenic purpura (ITP) relapsed or refractory to standard treatments. To better address this effect, a prospective randomized, multicenter, phase III study comparing treatment with Dexamethasone alone (arm A) vs Dexamethasone plus Rituximab (arm B) was started in July 2005 for adult patients with ITP according to the ASH guidelines. Main inclusion criteria were: age ≥ 18 years, untreated ITP, platelet (PLT) count ≤ 20 x109/L, HIV- HCV-HbsAg negativity, informed consent. Patients randomized to arm A received a single course of Dexamethasone 40 mg po on days +1, +2, +3, +4, while patients randomized to arm B received Dexamethasone (as in arm A) in association with Rituximab 375 mg/m2 iv on days +7, +14, +21, +28. Patients in arm A who failed to achieve a sustained response (SR) could be rescued with arm B treatment. The primary objective of the study was to compare SR, i.e. PLT ≥ 50 x 109/L at month + 6 of treatment. The secondary objectives were: the initial overall (OR= PLT ≥ 50 x109/L) and complete response (CR= PLT ≥ 100 x 109/L) by day 30 after starting treatment, respectively; the toxic profile. The statistical plan considered three interim analyses, after the first 50, 100 and 150 enrolled patients, with an estimated sample size of 198 patients (99 per arm). Table 1 summarizes the main demographic data and the results of efficacy and toxicity according to an intention to treat analysis of the first interim analysis. The toxic profile was characterized by only grade 3 adverse events (AE); no patient died during the study period. 16 patients of arm A were rescued with arm B. For this group SR was 81% and no patient experienced SAE or ≥ grade 3 AE. In accordance with the initial statistical plan of the study, which stated that patients’ recruitment would ceased if a ≥ 50% difference in sustained response was demonstrated, enrolment has been stopped in June 2007 with a total number of 103 randomized patients. This preliminary report indicates a significantly higher SR for arm B of treatment with no difference in toxicity profile. A final report will be prepared when the results on the entire study group will be available. Table 1 Therapy Arm A Arm B Statistics Patients 24 26 Male/female 11/13 10/16 p = NS Age (median ± SD) 54.54 ± 18.78 48.65 ± 15.10 p = NS Initial OR 15 (62.5%) 18 (69%) p = NS Initial CR 10 (42%) 16 (61%) p = NS SR 7 (29%) 21 (81%) p = 0.0001 SAE or grade 3 AE 3 (12.5%) 2 (8%) p = NS