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Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274.

Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusions of ofatumumab at the following doses: (A) one 100 mg and three 500 mg; (B) one 300 mg and three 1000 mg; (C) one 500 mg and three 2000 mg. Sixty-seven percent of the patients were Binet stage B, and the median number of previous treatments was 3. The maximum tolerated dose was not reached. The majority of related adverse events occurred at first infusion, and the number of adverse events decreased at each subsequent infusion. Seventeen (51%) of 33 patients experienced infections, 88% of them of grade 1-2. One event of interstitial pneumonia was fatal; all other cases resolved within one month. The response rate of cohort C was 50% (13/26), one patient having a nodular partial remission and 12 patients partial remission. In conclusion, ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia (CLL) in doses up to 2000 mg. Preliminary data on safety and objective response are encouraging and support further studies on the role of ofatumumab in CLL patients. This trial was registered at www.clinicaltrials.gov as no. NCT00093314.

Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20+ indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m2). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm. Conclusion Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials.

Abstract 3651 Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma accounting for 35–40%. Since the 1990s, The International Prognostic Index (IPI) has served as useful tool in daily treatment decision algorithm and in the design of clinical trials. In the last decade, improvement of overall survival (OS) has been demonstrated with R-CHOP-like regimens. In addition, the median life expectancy has increased substantially since the 1980'ies and more intensive treatment options like autologous BMT are performed successful up to 70 years of age. Thus, prognostic factors, including age, are susceptible to change over time. Material and methods: Patients with DLBCL diagnosed in the period 2000–2010 treated with Rituximab and CHOP-like chemotherapy were extracted from the Danish population-based Lymphoma Registry that covers > 97% of Danish lymphoma patients. Clinical and laboratory data at time of diagnosis were analysed, leaving out factors with < 75% completeness. Patients with transformed lymphoma, CNS involvement and HIV+ patients were excluded from the analysis. Results: 1990 patients (M:F ratio 1.26) were extracted from the LYFO database. The median age was 65 years, median follow-up was 54 months. Overall median survival was 9.7 years, with a 5 year OS of 65%. Analysis of age using 60, 65, 70, 75 years as cut-off, revealed 70 years as the optimal cut-point. Univariate analysis was performed including age, gender, stage, performance status, extranodal disease, LDH, albumin, immunoglobulin G, bulky disease, lymphocytes and haemoglobin. Only significant factors were included in a Cox proportional hazards model. Results for the entire patient cohort are shown in table I, and for patients Survival analysis of patients with 0–1, 2–3 and 4–6 risk factors showed 5-year survival values of 90%, 71% and 45% respectively (left figure). For patients Conclusion: Two decades after the introduction of the IPI, age, performance status and LDH are still some of the most powerful prognostic factors in DLBCL. Age cut-off at 70 years is meaningful in reflecting clinical practice and, in our analysis, albumin and IgG added significant prognostic importance. In addition, for patients younger than 70 years, male gender is an adverse prognostic factor. Disclosures: No relevant conflicts of interest to declare.

Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) –positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL.

Purpose Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients. DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001). The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001). DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP. Conclusion The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.

An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m(2) ), doxorubicin (50 mg/m(2) ), prednisone (100 mg days 3-7) and vincristine (1·4 mg/m(2) ) (O-CHOP), as frontline treatment for follicular lymphoma (FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg (n = 29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores in the 500- and 1000-mg dose groups, respectively. Overall response rate was 90% for the 500-mg group and 100% for the 1000-mg group. 62% of patients achieved complete response (CR)/unconfirmed CR (CRu). 76% of patients with FLIPI score 3-5 attained CR/CRu. Longer follow-up time is needed for analysis of survival end points. The most common Common Terminology Criteria grade 3-4 investigator-reported adverse events were leucopenia (29%) and neutropenia (22%). No deaths have been reported. O-CHOP was safe and efficacious in patients with previously untreated FL, including high-risk FLIPI groups. This trial was registered at www.clinicaltrials.gov (NCT00494780).

Background: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18–60 years with two or more risk factors (stage III–IV, elevated lactate dehydrogenase levels, performance status 2–4). To our knowledge, this is the first study comparing these two regimens in this patient group.Methods: We obtained data for the period 2004–2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety.Results: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P = 0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P = 0.02).Conclusion: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

Abstract 3565 Enteropathy-associated T-cell lymphoma (ETCL) is a rare lymphoma often, but not always, associated with celiac disease and characterized by poor prognosis when treated with conventional chemotherapy. In previous studies long-term survival has been achieved in only 10–20% of the patients. Limited data is available on the feasibility and efficacy of intensive induction chemotherapy followed by autologous stem transplantation (ASCT) in this rare lymphoma entity. We therefore specifically analysed the outcome of ETCL patients included in a large prospective phase II study (NLG-T-01) performed by the Nordic Lymphoma Group. The NLG-T-01 study included 160 patients with systemic alk-negative peripheral T-cell lymphoma over the period 2002–2007. The patients received CHOEP-14 × 6 followed by ASCT after BEAM or BEAC in responsive patients. The study included altogether 21 patients (13 %) with ETCL. There were 16 males and 5 females with a median age of 55 years (32-65) at diagnosis. Eighteen patients (86 %) had advanced disease, three patients (14 %) had a bulky tumour, nine patients (43 %) presented with B symptoms and four (19%) with elevated serum lactate dehydrogenase. Response status after three and six courses was CR or CRu in 67 % patients. Fourteen patients (67 %) received BEAM or BEAC supported by blood stem cell graft (median number of stem cells infused 5.4 × 106/kg). Of these, 6 patients relapsed with a median of 219 days from ASCT. Of the 7 patients (33%), who did not reach ASCT because of refractory/progressive disease, 5 died early due to lymphoma. At a median follow-up of 45 months, 10 patients (45 %) are alive. The progression-free survival is 40 %. One patient (5%) died due to early transplant-related cause (disseminated candidiasis). In this prospective study, intensive induction chemotherapy followed by ASCT was feasible in the majority of younger patients with EATL. In a subset of patients, who should clinically and biologically be further characterized, long-term outcome seems promising when compared to historical controls. Whether addition of other chemotherapeutic agents, antibodies such as alemtuzumab or other biologicals may further improve long-term outcome remains to be studied. Disclosures: No relevant conflicts of interest to declare.

International audience; The purpose of this phase 1-2 study was to investigate the association between pharmacokinetic (PK) properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukemia receiving 4 weekly infusions of ofatumumab. The ofatumumab concentration profiles were fitted well by a two-compartment model with different elimination rate constant at first infusion compared to the remaining infusions in line with the observed rapid and sustained B-cell depletion. Exposure to ofatumumab was linked to clinical outcomes: high exposure was associated with higher probability of overall clinical response and longer progression free survival. This association still remained statistically significant even when adjusting for relevant baseline covariates including tumor burden. The trial was registered at www.clinicaltrials.gov (NCT00093314).

8042^ Background: Ofatumumab (OFA) is a human antibody that targets a membrane-proximal epitope encompassing the small- and large-loop on CD20. Single-agent OFA has demonstrated clinical activity i...

Abstract 3566 Primary systemic T-cell lymphoma of anaplastic large cell type (ALCL) is an aggressive and predominantly nodal subtype of lymphoma, further subdivided based on expression of the ALK-protein, with ALK-pos ALCL occurring predominantly in younger patients and associated with a favourable prognosis. ALK-neg ALCL is believed to carry a prognosis similar to that of other nodal peripheral T-cell lymphomas and previous studies have shown long-term survival rates below 50%. There is retrospective data suggesting a benefit from ASCT in first-line treatment of this lymphoma subtype. We analyzed the outcome of ALK-neg ALCL patients included in a prospective phase II trial, NLG-T-01, conducted by the Nordic Lymphoma Group. The NLG T-01 trial enrolled 160 patients aged 18–67 years from the Nordic countries with systemic ALK-neg peripheral T-cell lymphoma within the period 2002–2007. The treatment schedule consisted of 6 courses of CHOEP-14 followed by ASCT (BEAM or BEAC) in responding patients. Patients >60 years received CHOP-14 as induction. Altogether, the trial included 31 patients with ALK-neg ALCL (19% of the study population). Median age was 56 years (22-65) with a male:female ratio of 2.4. Stage III-IV was found in 18 patients (58%), B-symptoms in 19 patients (61%) and 6 patients (19%) had a bulky lesion (>10cm). Pre-therapeutic serum lactate dehydrogenase was elevated in 18 patients (58%) and performance score was 2–4 in 10 patients (32%). After 3 and 6 courses of chemotherapy, response status was CR or CRu in 29% and 58% of the patients, respectively. In total, 24 out of 31 patients (77%) underwent BEAM/BEAC therapy followed by ASCT. Four patients did not respond or had disease progression during induction chemotherapy. The remaining 3 patients did not undergo ASCT for other reasons (mobilization failure, lung insufficiency, patient decision, respectively). Overall response rate after ASCT was 74% for the entire initial population and 96% for those undergoing ASCT. Median follow-up was 45 months. Six patients relapsed after ASCT. There was a total of nine deaths (29%): six due to lymphoma, two due to toxicity and one from second malignancy (colon cancer). With a median follow-up of 45 months, 3-year overall and progression-free survival values were 73% and 64%, respectively. Intensive chemotherapy followed by ASCT was feasible in the majority of the patients included in this prospective trial. Long-term outcome appears promising when compared to previously published data, with the survival curve suggesting a plateau. In ASCT eligible patients, intensive induction chemotherapy consolidated by upfront ASCT is an effective treatment that yields outcome results at least as good as those obtained in age-comparable patients with diffuse large B-cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract 331 Background and aims: Systemic peripheral T-cell lymphomas (PTCL) are malignancies responding poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by upfront high-dose chemotherapy supported by autologous stem-cell transplantation (HDT/ASCT) in PTCL, the Nordic Lymphoma Group conducted the, so far, largest PTCL-restricted prospective phase II study in previously untreated systemic PTCL. This is the final report of the NLG-T-01 study with a 5-years median follow up. Methods: Patients with previously untreated systemic PTCL aged 18–67 years were included. ALK-positive anaplastic large cell lymphoma (ALCL) cases were excluded. An induction regimen of six cycles of bi-weekly cyclophosphamide, doxorubicin, etoposide, vincristin and prednisone (CHOEP) was given. Age-based (>60 yrs) omission of etoposide was recommended. If in complete or partial remission, patients received high-dose chemotherapy with carmustine, etoposide, cytarabine and melphalan/cyclophosphamide (BEAM/BEAC) followed by HDT/ASCT. Results: A total of 166 patients with previously untreated PTCL were enrolled. Of these, 160 were histopathologically confirmed and included the following subtypes: PTCL-not otherwise specified (PTCL-NOS) (n=62; 39%), ALK-negative ALCL (n=31; 19%), angioimmunoblastic lymphoma (AIL) (n=30; 19%), enteropathy-associated T-cell lymphoma (n=21; 13%), panniculitis-like (n=6; 4%), T/NK nasal-type (n=5; 3%), and hepatosplenic (n=5; 3%). The M/F ratio was 2.0 and the median age 57 yrs (range 22–67 yrs). The majority of the cases presented with advanced-stage disease (81%), B-symptoms (59%) and elevated s-LDH (62%). Nevertheless, 71% of all patients had a good performance score (PS) (WHO 0–1) at inclusion. With regard to the International Prognostic Index (IPI), risk factor distribution was as follows: 1 factor n=45 (28%), 2 factors n=52 (32%), 3 factors n=30 (19%), 4–5 factors n=33 (21%). Of the 160 patients, a total of 114 (71%) underwent HDT/ASCT with 90 in complete remission at 3 months post-transplant. Early failures occurred in 26% of the patients. The treatment related mortality was low (4%). At a median follow-up of 60 months, 83 patients were alive. The median follow-up for deceased patients (N=77) was 9 months. The consolidated 5-yr overall (OS) and progression-free survival (PFS) values for the entire cohort were 51% and 44%, respectively. Best results were obtained in ALK-negative ALCL with 5-yr OS and PFS of 70% and 61%, respectively. IPI was a useful overall prognostic discriminator for the low/low-intermediate vs. intermediate-high/high groups with regard to 5-yr OS (p=0,047) and 5-yr PFS (p=0,029). If applied separately to each of the four major subtypes, IPI had a predictive value for OS in AIL (p=0,02) and for PFS in both AIL (p=0,02) and PTCL-NOS (p=0,03). The clinicopathological parameters that showed a significant impact on OS and PFS were: female gender (correlated with a better outcome), age (analyzed as continuous variable), PS≥2 (correlated with adverse outcome), and cytotoxic phenotype (correlated with adverse outcome in AIL). All these parameters retained their prognostic value at multivariate level, except for cytotoxic phenotype, where multivariate analysis could not be performed because of too small numbers. Conclusions: Dose-dense induction followed by HDT/ASCT is well tolerated and leads to long-term PFS in 44% of patients with systemic PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the present study population. Therefore, based on these results, dose-dense induction and HDT/ASCT should be considered in transplant-eligible PTCL patients. Disclosures: Jantunen: Genzyme: Honoraria.

7036 Background: SPC2996 is a novel Bcl-2 mRNA antagonist, based on the high affinity RNA analogue, Locked Nucleic Acid (LNA), being developed by Santaris Pharma for the treatment of CLL. Bcl-2 expression is typically high in CLL cells and epidemiologic data suggest that over expression of Bcl-2 is associated with a less favourable outcome in this disease. Methods: The study was an international, multicenter, dose escalating phase I/II study. Included were patients with relapsed or refractory Chronic Lymphocytic Leukemia requiring therapy, with a screening blood sample showing circulating lymphocyte counts of > 5×109/L and expressing the phenotype CD5+CD20+CD23+. Number of patients: 3 at the first two dose levels and 6 at the following levels. The patients received 6 intravenous infusions over a 2 week period with a 6 months follow up period. Assessments included: physical examinations, ECG, CT-scan, flow cytometry, PK, mRNA Bcl-2, clinical chemistry and hematology. Results: A total of 25 patients have been treated with the last patient completing treatment on 29 September 2006. Final data will be presented at ASCO. Preliminary data show a patient population with mean age 63.6 years; 68 % male; median 6.5 years of disease; median 3 prior therapies. Dose escalation was stopped after group E (4 mg/kg/dose) due to 2 DLTs in this group. A decrease in lymphocyte count was observed in 6 out of 6 pts in group E, which started within 24 hrs of the first administration of the investigational drug. Four out of 6 pts showed a maximal reduction in lymphocyte count of = 50%. Lymph node data show a decrease in total lymph node SPD of = 50% in 1 out of 5 pt in group D (2 mg/kg) and 2 out of 4 pts in group E (4 mg/kg/dose). Conclusions: Treatment of CLL patients with SPC2996 gives promising results. In group E all patients responded with an immediate decrease in lymphocyte count after receiving the initial administration of 4 mg/kg. A new investigation has been started to explore other dosing regimens, giving a smaller number of higher doses. [Table: see text]

Systemic PTCL, with the exception of alk-positive anaplastic large cell lymphoma (ALCL), have a poor prognosis. ASCT has been shown to have a favourable impact on relapsed PTCL. Therefore, the NLG designed a prospective multicenter phase II study to evaluate the impact of a dose-intensified induction schedule (6 courses of two-weekly CHOEP) consolidated in 1st PR/CR with high-dose therapy (BEAM) followed by ASCT in previously untreated systemic PTCL. This is the largest prospective PTCL-specific trial published so far. Newly diagnosed non-primary cutaneous PTCL cases aged 18–67 yrs were eligible for enrollment. Cases of alk-positive ALCL were excluded. From Oct 2001 to Feb 2006, 99 histologically confirmed PTCL cases were included in the study: PTCL unspecified (n=41), alk-neg ALCL (n=24), AILT (n=15), enteropathy-type (n=12), panniculitis-like (n=3), T/NK nasal-type (n=2), hepatosplenic (n=2). The M/F ratio was 1.8 and the median age 55 yrs (range 20–67 yrs). Although almost 2/3 of the cases presented with advanced-stage disease (62%), B-symptoms (61%) and/or elevated s-LDH (63%), the majority of them (65%) had a good performance score (WHO 0–1) at diagnosis. Of the 77 patients, where information was available for all 6 induction courses, 68 (88%) were in CR (31) or PR (37) after the 3rd and 66 (86%) after the 6th course. A total of 58 patients (75%) went through ASCT indicating that at least a fourth of this younger patient cohort has a primary refractory disease and fails therapy before reaching the transplant. Treatment-related toxicity after both induction and high-dose treatment was manageable. Of the 58 transplanted patients, 50 (86%) were still in remission at re-evaluation short after transplant. In 39 patients follow-up data one year post-transplant were available: 30 are still in CR and 9 have relapsed, suggesting that post-transplant relapses probably account for another 25% of the original patient cohort. In conclusion, the present data indicate that a time- and dose-intensified schedule is feasible and effective in previously untreated systemic PTCL. Continuous remissions are not uncommon, but a longer follow-up is needed to further characterize long-term remission rates and evaluate their impact on time-to-treatment failure and overall survival.

Abstract 1632 Background: OFA is a fully human monoclonal antibody that binds to both the large and small extracellular loops of CD20. OFA is currently approved for patients (pts) with refractory chronic lymphocytic leukemia and has demonstrated activity in non-Hodgkin's lymphomas, including follicular lymphoma (FL). We previously reported results of a phase II study of OFA in combination with CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg daily for 5 days) chemotherapy (O-CHOP) in pts with previously untreated FL (Czuczman et al. Br J Haematol. 2012;157:438). We now report updated efficacy, safety and pharmacokinetic (PK) follow-up data for this study. This trial is registered at www.clinicaltrials.gov (NCT00494780). Methods: Fifty-nine pts with previously untreated FL were randomized to OFA 500 mg (n = 29) or 1000 mg (n = 30) on day 1, with CHOP on day 3, every 3 weeks for 6 cycles. The primary end point was overall response rate (ORR), as assessed by an independent end points review committee. Secondary end points included complete response (CR), progression-free survival (PFS), overall survival, adverse events (AEs) and PK. Follow-up assessments after therapy were done every 3 months (mo) until mo 12 and then every 6 mo until alternative FL therapy or mo 60. Positron emission tomography (PET) was done at baseline and 3 mo after last therapy. Blood samples for PK analyses were collected to determine OFA serum concentrations, and noncompartmental methods were used to estimate PK parameter values. Results: Fifty-eight pts received therapy; 1 pt in the 1000-mg group withdrew before initiation of therapy. The ORR was 90% for the 500-mg group (n=29) and 100% for the 1000-mg group (n=29); 55% of pts achieved CR or unconfirmed CR (CRu), including 67% of pts with a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3–5. At baseline, 57 pts were PET positive, and 49 pts underwent repeat PET scans after therapy. Forty of 49 pts (82%) became PET negative, including 27 of 29 (93%) pts who achieved CR/CRu and 13 of 20 pts (65%) who achieved partial response (PR). With a median follow-up of 33.8 mo, the median PFS for the 500-mg group was 27.6 mo and the median PFS for the 1000-mg group was not reached (P=0.46). Median PFS for pts with FLIPI scores of 0–1 (n=17), 2 (n=20) and 3–5 (n=21) was not reached, 27.6 mo and 27.6 mo, respectively (P=0.68). Median PFS for pts (n=32) who achieved CR/CRu was also not reached and was 28.3 mo for pts (n=23) achieving PR. Median PFS for PR pts who were PET positive and PET negative after therapy was not reached and 28.3 mo, respectively. No deaths have been reported. No hematologic serious AEs (SAEs) were experienced during the follow-up period. During the follow-up period, non-hematologic SAEs were reported in 1 pt in the 500-mg group (pneumonia) and 5 pts in the 1000-mg group (abdominal hernia, erysipelas, intervertebral disc protrusion, meniscus lesion and vulval cancer); none were ofatumumab-related. After repeated dosing, OFA clearance values were 6.3 and 5.9 mL/h, and half-life values were 27.2 and 26.8 days in the 500-mg and 1000-mg groups, respectively. Conclusions: O-CHOP achieved durable remissions in previously untreated pts with FL. There were no observed PK or PFS differences between the 500-mg and 1000-mg arms, but the study was not powered to detect such differences. O-CHOP was effective in pts with high-risk FLIPI scores, and CR/CRu and PFS rates were not affected by FLIPI score. PET status after therapy did not predict PFS in responding pts, although the study was too small to make such a determination. These results indicate that O-CHOP should be studied as a therapy for FL pts with high-risk FLIPI scores. Disclosures: Czuczman: GlaxoSmithKline: Advisory board Other, Honoraria. Off Label Use: Ofatumumab in follicular lymphoma. Belada:GlaxoSmithKline: Research Funding. Mayer:Roche: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding. Gupta:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Employment, Equity Ownership. Winter:GlaxoSmithKline: Employment, Equity Ownership. Goldstein:GlaxoSmithKline: Employment, Equity Ownership. Jewell:GlaxoSmithKline: Employment, Equity Ownership. Lisby:Genmab: Employment, Equity Ownership.