Hong, Fangxin

Abstract Abstract 1603 Background: We have previously reported similar outcomes for patients with bulky stage I or II mediastinal HL treated with combined modality therapy either with ABVD + radiotherapy or the Stanford V regimen in the North American Intergroup trial E2496 (Advani et al, ASH 2010 abstract 416). In the current analysis, we compare the patterns of failure between the two groups. Methods: Patients with stage I/II bulky mediastinal HL (maximum mediastinal mass width > 1/3 of intrathoracic diameter) were randomized to receive chemotherapy (CT) on either Arm A (ABVD x 6–8 cycles administered q 28 days) or Arm B (12 weeks of Stanford V administered weekly). Two-3 weeks after completion of chemotherapy all patients received modified involved field radiotherapy (RT) (36 Gy) delivered to the mediastinum, hila, and supraclavicular regions. Patients on Stanford V arm also received involved field RT to any other sites ≥ 5 cm at diagnosis. Patients were assessed 3, 6 and 12 months after completing RT with computed tomography scanning and then every 6 months for 5 years. The primary end points were failure free survival (FFS) and overall survival (OS). Disease progression was defined as 'in-field', 'distant' or both relative to the radiation fields prescribed in the E2496 protocol. Distant sites of failure were further characterized as intra-thoracic, intra-abdominal or other (bone, bone marrow and axillae, if not previously irradiated). Results: Two hundred and sixty-seven patients were randomized: 136 on the ABVD arm and 131 on the Stanford V arm. Patient characteristics were well matched with no differences between two arms in overall response rates (ORR), FFS and OS. (Advani et al ASH 2010 abstract 416). At a median follow up of 5.5 years 40 patients have relapsed with no difference in ABVD (n=18, 13%) versus Stanford V (n=22, 17%) (p=0.49). Central review of RT fields available in 37/40 patients found major violations with under treatment of tumor noted in 7/37 (19%). Patterns of failure are shown in Table 1. There were no differences in patterns of relapse for the two study arms. In-field relapses occurred in <10% in both study arms. Conclusion: For patients with stage I/II bulky mediastinal HL, combined modality therapy with either ABVD +RT or the Stanford V regimen results in excellent disease control. In-field relapse was uncommon. These results set a benchmark for assessing ongoing trials omitting RT in patients with stage I/II bulky mediastinal HL. Future research efforts should focus on risk stratification to identify the small subset of patients who are likely to fail standard upfront therapy. US cooperative group efforts in this subset of patients are ongoing that use interim PET-CT imaging based risk-adapted strategies. Disclosures: Horning: Genentech: Employment, Equity Ownership.

Abstract Abstract 2687 Background: Patients with early stage (Stages I, II) diffuse large B cell (DLBCL) have been traditionally treated with either CHOP x6 alone or with CHOP followed by involved field external beam radiotherapy (IFRT). With the demonstration of the superiority of rituximab CHOP (RCHOP) in advanced stage DLBCL, RCHOP has been adopted as the chemoimmunotherapy standard of care in early stage disease with or without IFRT. Radioimmunotherapy (RIT) has the advantage of delivering high-energy, short path length radiation in a targeted approach using an anti-CD20 antibody as the carrier. Thus, radiation is potentially targeted to microscopic sites outside of known disease. Goals: To evaluate the complete response (CR) rate and functional CR rate (CR or CRu/PR and PET negative) to a treatment regimen of RCHOP followed by 90Y-ibritumomab tiuxetan (Zevalin, Spectrum Pharmaceuticals) radioimmunotherapy (RIT); only patients not achieving PET negative status after RIT were to be given IFRT. The study goal was to achieve a functional CR rate of ≥75%. Patients and Methods: Eligible patients were those with new, untreated Stages I or II DLBCL as determined by standard CT scanning, adequate blood counts, creatinine and bilirubin <2.0 mg/dl, cardiac ejection fraction >45%, and a performance status 0–2. Stage I patients were required to have ≥1 adverse risk factor (≥60 years, bulky disease, elevated LDH or PS2). Patients received standard RCHOP21 × 2 cycles and then were restaged. Patients in CR received 2 additional cycles; those in PR or CRu received 4 additional cycles. At end of RCHOP a PET scan was repeated and centrally reviewed; those with a PR or functional CR proceeded to Zevalin RIT 0.4 mCi/kg (maximum 32 mCi) within 12 weeks of the last RCHOP. Patients were restaged 12 weeks post-RIT; PET negative patients were observed without maintenance; PET positive patients received 30Gy involved field radiation and then were restaged. Descriptive statistics were used to summarize the patient characteristics, treatment and response. The Kaplan-Meier method was used to estimate failure rates. Results: Between Dec 2004 and Nov 2008, 62 patients were enrolled; after pathology review 53 were considered eligible. 42% (22/53) patients were stage I/IE; 58% (31/53) were stage II/IIE. 57% (30/53) received 6 cycles of RCHOP; 40% (21/53) received 4 cycles; and 2 patients received 1 and 2 cycles, respectively. After immunochemotherapy, 79% (42/53) were in functional CR and 19% (10/53) PR; 1 was unevaluable. Of the 53 eligible patients who completed RCHOP therapy 91% (48/53) proceeded to RIT. After RIT, 87% (46/53; 95% CI: 75–95) were in CR/CRu and 89% (47/53; 95% CI:77–96%) were in functional CR. One patient proceeded to IFRT. The median follow-up is now 4.3 years. Seven (13%) of patients have had tumor progression but only 2 have died (1 of disease). At 4 years, 88% of patients remain progression free and 98% remain alive (Fig 1,2). The median has not been reached for either PFS or OS. There has been one case of myelodysplastic syndrome. Conclusions: Combination immunochemotherapy and RIT is an active regimen for patients with early stage DLBCL. Nearly all patients will achieve functional CR without the requirement of IFRT. The regimen of RCHOP and RIT for early stage DLBCL is worthy of further study. Disclosures: Witzig: Spectrum: Membership on an entity's Board of Directors or advisory committees, Research Funding, uncompensated Other. Off Label Use: Use of Zevalin in treating patients with Stage I-II DLBCL. Kahl:Roche: Consultancy; Genentech: Consultancy, Research Funding. Horning:Genentech: Employment; Roche: Equity Ownership.

Abstract Abstract 416 Background: Standard therapy for locally extensive Hodgkin Lymphoma (HL) defined as stage I/II with bulky mediastinal disease [mediastinal mass ratio (MMR) > than 1/3 of the chest diameter on standing postero-anterior chest x-ray or 10 cm on computerized tomography] is combined modality therapy (CMT). E2496 was a North American intergroup, randomized phase III study comparing ABVD versus the Stanford V regimen for patients with locally extensive and advanced stage HL. In this subgroup analysis we compare two CMT approaches, ABVD + radiotherapy (RT) and the Stanford V regimen, in patients with stage I/II bulky mediastinal HL. Methods: Patients with stage I/II HL bulky mediastinal disease were randomized to receive chemotherapy (CT) on either Arm A (ABVD × 6–8 cycles administered q 28 days) or Arm B (12 weeks of Stanford V, administered weekly). Two-3 weeks after completion of chemotherapy, modified involved field RT was delivered at 36 Gy to the mediastinum to patients on ABVD as well as Stanford V. Patients on Stanford V also received involved field RT to any other sites >5 cm at diagnosis. The primary endpoint was failure free survival (FFS) defined as the time to either progression/relapse or death. The log-rank test was used to compare FFS and OS (overall survival) for all eligible patients. Results: Of the 812 eligible patients with advanced HL enrolled on the study 267 had locally advanced bulky mediastinal disease: 136 on ABVD and 131 on Stanford V. Patient characteristics between the two randomized groups were well matched with a median age of 30 years and 86% had stage II disease. On ABVD 61% of patients received 6 cycles, 29% 8 cycles of CT and 77% required some dose modification. In Stanford V 97% completed the assigned 12 weeks of CT and 76% required some dose modification. 82% received RT per protocol in ABVD versus 88% in Stanford V. The overall response (CR+PR) was 82% in ABVD and 86% in Stanford V. At a median follow-up of 5.47 years, there are 19 failures and 6 deaths in the ABVD group and 25 failures with 9 deaths in the Stanford V group. We failed to detect statistically significant differences between ABVD +RT and Stanford V for FFS (5y 85% versus 77% p=0.13, HR=1.56 95% CI (0.87, 2.88) and OS (5y 95% versus 92% p=0.31, HR=1.69 95% CI (0.60, 4.75). No difference in hematologic toxicity was observed between the two arms. Evaluation of pulmonary function and patterns of failure are pending. Conclusions: For stage I/II patients with bulky mediastinal disease, CMT with either ABVD +RT or the Stanford V regimen results in high cure rates and is highly effective. ABVD for 6–8 cycles plus 36 Gy RT remains the US standard of care. Longer follow up is required to assess RT related late effects. Future research efforts should focus on risk stratification to identify; a) the 15–20% of patients destined to relapse after standard therapy and evaluate treatment intensification strategies and b) the 80–85% of patients who are cured with standard therapy and determine whether a subset can achieve the same excellent outcomes with a reduction or elimination of radiation. Planned US cooperative group trials will address these questions, using ABVD as the chemotherapy backbone in conjunction with interim PET imaging for risk stratification. Disclosures: Blum: Seattle Genetics: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Horning:Genentech: Employment.

Abstract Abstract 589 Background: The initial results of this intergroup trial with median follow-up of 3.5 years (yrs) were previously reported (J Clin Oncol 24:3121, 2006). We present updated results with median follow-up of 9.4 yrs from induction therapy randomization, and 9.0 yrs from maintenance randomization. Methods: 632 patients (pts), age >60 yrs, with DLBCL were randomized to CHOP+rituximab 375 mg/m2 IV, administered Day -7, -3, and two days before cycles 3/5/7 (if given) (R-CHOP), versus CHOP, for two cycles beyond best response for 6–8 cycles total. Pts were stratified by the International Prognostic Index (IPI) (<3 vs >3). 415 pts responding to R-CHOP or CHOP were then randomized to maintenance rituximab 375 mg/m2 weekly times 4, every 6 months for 2 yrs starting 4 weeks after the last chemotherapy (MR, n=207), or observation (OBS, n=208). Results are presented for the 546 (267 R-CHOP; 279 CHOP) pts for induction, and 352 (174 MR; 178 observation) evaluable, centrally reviewed, maintenance pts. Failure-free survival (FFS) was the primary endpoint. The stratified weighted Cox regression was used to remove the effect of MR in comparing induction treatment, and stratified log-rank test used to assess maintenance effect. Results: Baseline characteristics and response to induction were balanced. 9-yr FFS and OS) are 35% and 44% for R-CHOP, and 25% and 37% for CHOP. Compared with CHOP, R-CHOP significantly prolonged FFS (p=.008), but not OS (p=.11). Pts were categorized into low-risk (LR) and high-risk (HR) groups according to their IPI (<3 or 33) (LR, n=217; HR, n=327). A significant difference in the effect of induction therapy was observed for high-risk patients only for FFS (p=0.02, HR=0.61, 95% CI, 0.51 to 0.93) but not for OS. MR significantly prolonged FFS (log-rank p=0.018, HR=0.71, 95%CI, 0.54 to 0.94), but not OS (p=0.44, HR=0.89, 95%CI, 0.65 to 1.20). A significant interaction between maintenance and induction therapies was observed in that MR significantly prolonged FFS after CHOP (p=0.003, HR=0.56, 95%CI, 0.38 to 0.82), but not after R-CHOP (p=0.89, HR=0.97, 95% CI, 0.64 to 1.47). There was no OS difference with MR after CHOP (p=0.19, HR=0.76, 95% CI. 0.50 to 1.15) or R-CHOP (p=0.77, HR=1.07, 95% CI, 0.68 to 1.68). Median time to failure after maintenance randomization following CHOP+MR was 9.5 yrs vs 2.0 yrs for CHOP+OBS (p=0.003) and following R-CHOP+MR was 8.5 yrs vs 7.5 yrs for R-CHOP+OBS (p=NS). Proportionately more treatment failures occurred within 2 yrs after CHOP+OBS (73%) compared to CHOP+MR (47%), p=0.01. In contrast, the proportion of failures within 2 yrs was similar for R-CHOP+OBS (38%) and R-CHOP+MR (36%), p=NS. Conclusions: Initial R-CHOP therapy, as compared with CHOP, resulted in improved DFS and FFS for older DLBCL pts. MR after CHOP, but not after R-CHOP, significantly prolonged time to failure but did not prolong OS. However, FFS was 42% at 9 yrs among R-CHOP responders, with or without MR. Future treatment strategies should build upon these findings in this older patient population, often with significant co-morbidities. Disclosures: Morrison: merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Speakers Bureau; amgen: Consultancy, Speakers Bureau; genentech: Speakers Bureau; pfizer: Speakers Bureau. Fisher:roche: Consultancy. Horning:Genentech: Employment.

Abstract Background: Despite advances in chemotherapy, R/R HL remains a significant clinical problem with over 1,000 primarily young lives lost annually. HL is a unique tumor in which a small number of malignant Hodgkin Reed-Sternberg (HRS) cells propagate an immunosuppressive microenvironment that augments HRS growth and survival. We hypothesized that immune checkpoint inhibitor therapy could activate the tumor immune microenvironment, while the CD30 expressing HRS cells could be targeted by brentuximab vedotin (BV), thereby overcoming tumor cell resistance and deepening clinical responses. E4412 is a phase 1 ECOG-ACRIN sponsored study of the combination of BV and the checkpoint inhibitors ipilimumab (IPI) and nivolumab (NIVO) in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). Here we report the data on the patients treated with BV + IPI, the first cohort of the study. Methods: Patients with biopsy proven R/R HL were treated with BV 1.8mg/kg and two escalating doses of IPI: 1 mg/kg or 3mg/kg. After safety was determined an expanded cohort was treated with BV 1.8mg/kg IV and IPI 3mg/kg IV. The schedule consisted of BV administered every 21 days for 16 cycles and IPI every 21 days x 4 doses and thereafter every 3 months for up to a year. Dose limiting toxicity (DLT) was defined for purposes of dose escalation within the first cycle of therapy. Patients are followed for toxicity up to 30 days beyond their last treatment. Results: As of 7/2015 19 of 23 planned patients have been treated with BV + IPI. We report the data on the full dose escalation population (13 patients: Dose level 1 (6), Dose level 2 (7)). The median age was 33 years (range: 20-49). Seven patients were male. Patients were heavily pretreated with a median of 4 prior therapies (2-13). Fourpatients had prior treatment with BV; 8 patients had prior SCT (7 autologous, 1 allogeneic). Safety: Overall the regimen of BV + IPI was extremely well tolerated with no DLTs noted during dose escalation. Toxicities considered at least possibly related to drug during any cycle of treatment are shown according to grade in Table 1. The most common treatment related adverse events were: diarrhea, rash, and peripheral sensory neuropathy. Other AEs of interest included: alopecia, transaminitis, and uveitis. Grade 3 and 4 treatment related adverse events (AEs) included: Dose level 1: one grade 3 infusion reaction, which led to a protocol amendment to include premedication, no further grade 3 infusion reactions were noted; Dose level 2: one each: grade 3 rash, vomiting, and peripheral sensory neuropathy, and one grade 4 thrombocytopenia in patient with pre-existing thrombocytopenia. Response: For the 12 evaluable patients, the overall response (ORR) for the combination of BV + IPI was 67% with a complete response (CR) rate of 42% (5 of 12 patients). An additional 2 patients had stable disease (SD) giving a clinical benefit rate of 83%. Three of 5 of the CRs occurred at dose level 1 (1mg dose of IPI). The median progression free survival (PFS) is 0.74 years with a median follow-up of 0.66 years. Conclusion: In this first reported study of the combination of checkpoint inhibitor and ADC, toxicity was low, primarily grades 1 and 2. In a heavily pretreated patient population, 33% of whom had had prior BV and 67% of whom were s/p ASCT, the ORR of 67% and CR rate of 42% suggests a potential deepening of response compared to monotherapy. More than half of these CRs occurred at 1mg of IPI suggesting that in combination with ADC, low doses of immune stimulation may be highly active. Optimization of this combination strategy is planned with ongoing accrual to cohorts receiving BV + NIVO, and BV + IPI + NIVO. Data will be updated to include the full BV + IPI cohort by the time of the annual meeting. Table 1. Common and Immune Toxicities Toxicity Type Dose Level 1 (n=6) Dose Level 2 (n=7) Grade Grade 1,2 3 4 5 1,2 3 4 5 (n) (n) (n) (n) (n) (n) (n) (n) Fatigue 5 - - - 3 - - - Fever 1 - - - 3 - - - Pain 2 - - - 3 - - - Alopecia 2 - - - 1 - - - Pruritus 1 - - - 2 - - - Rash maculo-papular 4 - - - 2 1 - - Diarrhea 4 - - - 4 - - - Dyspepsia 2 - - - 1 - - - Nausea 6 - - - 4 - - - Vomiting 3 - - - 2 1 - - Papulopustular rash 1 - - - 1 - - - Alanine aminotransferase increased 3 - - - 3 - - - Aspartate aminotransferase increased 3 - - - 2 - - - Platelet count decreased - - - - - - 1 - Anorexia 3 - - - - - - - Headache 2 - - - 2 - - - Peripheral sensory neuropathy 5 - - - 4 1 - - Dry eye 2 - - - - - - - Uveitis 1 - - - - - - - Cough 2 - - - 1 - - - Disclosures Diefenbach: Molecular Templates: Research Funding; Immunogen: Consultancy; Celgene: Consultancy; Idera: Consultancy; Jannsen Oncology: Consultancy; Gilead: Equity Ownership, Research Funding, Speakers Bureau; Incyte: Research Funding; Genentech: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Off Label Use: Presentation will discuss the experimental use of the checkpoint inhibitor Ipilimumab in relapsed/refractory Hodgkin lymphoma.. Cohen:Celgene: Consultancy; Millennium: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Consultancy; BMS: Research Funding; Janssen: Research Funding. Robertson:Eli Lilly: Equity Ownership. Fenske:Pharmacyclics: Honoraria; Seattle Genetics: Honoraria; Millennium/Takeda: Research Funding; Celgene: Honoraria. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding.

Abstract Background The international prognostic score (IPS) (Hasenclever et al., NEJM 1988) uses 7 factors (age> 45, male sex, hemoglobin<10.5, stage IV, leukocytosis > 15,000, and lymphopenia< 600) to predict a 5 year freedom from progression (FFP) of 42%-84% and overall survival (OS) of 56%-89% for patients with advanced HL. Constructed from a retrospective analysis of patients treated before 1992, the IPS continues to be the most commonly used risk stratification index for advanced HL. Recent studies suggest that the predictive range of the IPS has narrowed due to improved outcomes of patients treated with current therapy (Moccia et al. JCO 2012). In this report we prospectively evaluated the ability of the individual components of the IPS to predict outcome in patients enrolled on the US Intergroup trial E2496. Methods All seven IPS (IPS-7) variables were recorded for all patients at study entry. FFP was defined as the time from study entry to disease progression or relapse; deaths that occurred during remission that were not preceded by disease progression/relapse were censored. OS was defined as the time from study entry to death from any cause. Kaplan-Meier methodology was used to construct survival curves. Univariate and multivariate analysis (MVA) was performed using Cox proportional-hazards models. We subsequently constructed an alternative prognostic score utilizing the factors which were significant on MVA (PS-3). Results From 1996-2006, 854 patients with advanced HL, were randomized to treatment with either ABVD or Stanford V, with no significant differences in outcome (Gordon et al, JCO 2013). While the IPS-7 remained prognostic it did not stratify the lowest risk patients (0-1 risk factor) or patients with 3-5 risk factors, as its predictive range was narrowed due to improved clinical outcomes (Fig 1a and 2a). Table 1 shows the univariate and multivariate analysis for IPS-7 and outcomes. In contrast to the original IPS-7, on MVA, only two factors, hemoglobin and stage were significant for FFP, and three factors for OS: hemoglobin, stage, and age. We then evaluated a new 3 factor score (PS-3) utilizing variables significant on the MVA. The PS-3 was significant for both FFP (p=0.0001) and OS (p<.0001) and clearly separated patients into 4 distinct risk groups with either: 0, 1, 2 or 3 risk factors. The five year FFP was 83%, 74%, 68%, and 63% and OS was 95%, 85%, 75%, and 52% for patients with 0, 1, 2, and 3 risk factors, respectively (Table 2, Fig 1b and 2b). Conclusion In E2496, for patients with advanced HL, the PS-3 may stratify patients more clearly compared to IPS-7 and provide a simpler model to assess risk. Studies comparing PS-3 with IPS-7, and are ongoing. The incorporation of novel biomarkers and biologic factors into PS-3, as well as validation with other data sets is warranted. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1671 Poster Board I-697 Background Bevacizumab (Avastin), a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF-A), is approved in combination with chemotherapy in lung, colorectal, breast and brain cancers. VEGF-A expression is reported in all lymphoma subtypes, with strongest expression in PTCL. Given the relatively poor prognosis of PTCL with standard therapy, we combined bevacizumab (A) with CHOP in the ECOG 2404 phase II trial. Methods Untreated PTCL pts with a normal baseline cardiac ejection fraction received bevacizumab 15 mg/ kg IV and CHOP chemotherapy on day 1 for 6-8 cycles. Patients (pts) with CR/PR/SD received maintenance therapy with bevacizumab 15 mg/ kg IV q 3 weeks for 4 cycles. Due to the reported 3.7% incidence of cardiac toxicity associated with bevacizumab in metastatic breast cancer pt previously exposed to anthracyclines (Avastin package insert), cardiac function was monitored prospectively with ejection fraction (EF) determination at the completion of A-CHOP prior to the start of bevacizumab maintenance. Results Among 33 pts who came off study, toxicity data are available for all and coded using CTCAE Version 3.0. 22 received at least 4 cycles of A-CHOP (median treatment duration 3.6 months (< 1-10.6 months). One or more designated cardiac toxicities were recorded for 5 of these 22 pts. Congestive heart failure (CHF), defined as grade 2-4 left ventricular dysfunction was recorded in 4 pt (18%, 90% CI 5.2%-40.3%): grade 4 (n=1), grade 3 (n=3). In 3 pts clinical CHF occurred after A-CHOP x 6 and in one during bevacizumab maintenance after A-CHOP x 8. The median time to development of a cardiac adverse event was 5 months (3.5 – 8.8 months). One pt required a ventricular assist device in addition to medical management. In 3 of the 4 pts, ongoing medical management for CHF has been required. Other cardiac toxicities included ventricular arrhthymia (one grade 4, one grade 2), and one grade 2 cardiac troponin elevation. In addition, one patient experienced sudden death of uncertain cause. Three pts developed thromboses or embolic toxcities (two grade 4 and one grade 3). Conclusions We observed four cases of clinical CHF early after cumulative doxorubicin doses of 300-400 mg/m2 in our study, The incidence of CHF among study patients who received 4 or more A-CHOP cycles is concerning and suggests that bevacizumab may potentiate the adverse cardiac effects of anthracyclines, resulting in clinically significant toxicity. Careful monitoring of cardiac function is warranted in ongoing trials combining bevacizumab and doxorubicin in lymphomas and solid tumors to assess long-term safety and better understand underlying mechanisms and risks. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 3705 Improved outcomes were reported in USA studies in DLBCL (Habermann et al. J Clin Oncol 2006) in a two-staged randomized study of R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) versus CHOP with a second randomization assignment to maintenance rituximab (MR) or observation (OBS) (E4494) and in follicular lymphoma (FL) in patients in a trial with CVP (cyclophosphamide, vincristine, and prednisone) followed by randomization to MR versus OBS in advanced-stage indolent lymphoma (E1496) (Hochster et al. J Clin Oncol 2009). The details of the treatment regimens have been previously described. The German High Grade Lymphoma Study Group has reported differences between men and women in outcomes in DLBCL with improved outcomes in women treated with rituximab (Müller et al. Blood 2012). Methods: Survival outcomes by sex were analyzed using a stratified weighted cox regression, removing the effect of maintenance rituximab in DLBCL (E4494), and a log-rank test in patients with follicular histology (E1496). A Cox regression model was used to evaluate the differences between males and females together with weight (below or above the median). Wilcoxon test and Fisher's exact test were used to compare medians and proportions, respectively. Results: In DLBCL, there were 273 eligible males and 273 females. The median age was 69 in males and 70 in females. There were no differences in baseline patient characteristics among the male and female populations. 138 males and 129 females were treated with R-CHOP. There was no difference in treatment received, with 83% females and 75.3% males receiving 6 cycles or more of R-CHOP treatment (p=0.14). The complete remission (CR) and partial remission (PR) rates after RCHOP were higher in females (82.6%) versus males (71.5%) (P = 0.04). With a median follow-up of 9.45 years, the failure free survival (FFS) and overall survival (OS) were improved in females (P = 0.02, 0.002; HR=0.63, 0.54) compared with males in the R-CHOP group. The outcomes were not different in the CHOP group for FFS (P = 0.81) or OS (P= 0.57) between males and females. Within the R-CHOP group, the failure free survival (FFS) was significantly different between women and men (P = 0.002) and body weight (P = 0.03), but only female sex (P = 0.001) was significant and not weight (P = 0.26) for OS. Of 282 evaluable patients with advanced-stage follicular lymphoma who received initial treatment with CVP, 115 patients were randomly assigned to MR and 113 to OBS. 120 patients were male, and 108 were female. The median age was 58 years in the MR arm and 54 years in the OBS arm. At a median follow-up of 8.04 years, MR markedly improved the PFS (P=0.003) compared with OBS. There were no differences in PFS (P= 0.17) between males and females treated with MR or OS (P = 0.27). In conclusion, in induction therapy with rituximab in DLBCL there is a sex dependent effect with rituximab with males benefiting less than females. In contrast, in patients with follicular lymphoma treated with chemotherapy followed by maintenance rituximab, there were no differences. The differences in outcomes in patients of different sex with DLBCL treated with immunochemotherapy and FL treated with maintenance rituximab will require further analysis of multiple clinical and biologic variables. Disclosures: Fisher: Roche: Advisory Board Other. Cheson:Genentech: Consultancy. Kahl:Genentech, Roche: Consultancy, Research Funding. Horning:Genetech, Roche: Employment, stock (Roche) Other.