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4973 Background/Rationale: Rituximab is an anti-CD-20 monoclonal antibody used in the management of lymphoproliferative disorders. Rituximab is indicated in maintenance therapy for follicular cell lymphoma and can be administered once every 2 months, once every 3 months, or weekly for 4 weeks every 6 months. The use of maintenance rituximab has improved progression free survival and overall survival in low grade follicular lymphomas. Although rapid rituximab infusions have been studied extensively, there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas. Herein we report our experience with rapid infusion rituximab in patients receiving maintenance therapy. Methods: All patients who received rapid infusion rituximab as maintenance therapy for low grade lymphoma between December 2007 and June 2011 were included. Patients were considered eligible for rapid infusions if they tolerated previous rituximab infusions and presented with a peripheral lymphocyte count of less than 4.8 k/μl. Rapid rituximab infusions were administered over 90 minutes (150 mL/hr for 30 minutes and then increased to 275 mL/hr until completion). Patients were monitored for signs and symptoms of reactions. In case of an infusion reaction supportive care medications were readily available. Demographic, laboratory and clinical data were collected. Adverse events were assessed through vital signs, symptoms of infusion related reaction and supportive care measures administered and graded according to the Common Terminology Criteria for Adverse Events Version 4. The primary and secondary objectives of this retrospective study were to evaluate the incidence of grade 3/4 and all grade infusion reactions with rapid rituximab infusions during maintenance therapy, respectively. Maintenance schedules were also compared with regards to incidence of infusion reactions. Results: A total of 105 patients received 629 rapid rituximab infusions. Patient demographics, laboratory, and clinical data are summarized in Table 1. All patients were eligible for rapid infusion rituximab according to institutional criteria. Two grade 2 infusion reactions and 4 grade 3 reactions were reported (1 patient experienced a grade 2 and 3 reaction); however none of these patients required hospitalization. All 5 patients received pharmacological and/or supportive care to relieve the symptoms associated with the reaction. Of these 5 patients, 3 patients went on to receive rapid infusions of rituximab; 2 patients were switched to standard infusion per physician request. The sample size was too small to determine if a correlation existed between infusion related reactions and the schedule of maintenance rituximab. Conclusion: The rapid infusion of rituximab in patients receiving maintenance therapy is well tolerated with minimal incidence of infusion-related reactions. Although the sample size was insufficient to assess differences in adverse effects according to the maintenance schedule, the low overall incidence of adverse effects suggests that rapid rituximab infusions are well tolerated regardless of maintenance schedule. Our study concludes rapid infusion rituximab is a safe and feasible option for maintenance therapy. Disclosures: Ho: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Maintenance Rituximab Therapy in Non-Hodgkin's Lymphoma. Cultrera:Genentech: Speakers Bureau. Sotomayor:Genentech: Membership on an entity's Board of Directors or advisory committees. Wetzstein:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees.

4017 Background: Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease sharing features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). FDA approved indications for azacitidine and decitabine include CMML as subset of MDS. Fewer than 10 patients with CMML, however, were treated in each of the original studies. In this study we report our institutional experience of azacitidine treatment of CMML patients. Methods: This was a retrospective review of CMML patients who received azacitidine at Moffitt Cancer Center. The primary endpoint was determining response rate to azacitidine utilizing International Working Group 2006 criteria (IWG 2006). Secondary objectives were to assess treatment tolerance and overall survival. Descriptive statistics were used for baseline characteristics and response rates. Kaplan-Meier estimates were used for evaluation of overall survival. Results: Between July 2004 and December 2009, 35 CMML patients treated with azacitidine were identified. Table-1 summarizes baseline characteristics of those patients. Based on Dusseldorf CMML risk criteria one patient (2.9%) was low risk, 17 (48.7%), intermediate, 7 (20%) high risk and 10 (28.6%) were unknown. According to MD Anderson CMML risk model, 11 (31.4%) were low risk, 12 (34.3%) int-1, 2 (5.7%) int-2, 1 (2.9%) high risk and 9(25.7%) unknown. The median number of azacitidine cycles was 6.0 (1-34) The best response rates by IWG 2006 criteria were complete response (CR) 5 (14.3%), marrow CR 4 (11.4%), partial response (PR) 1 (2.9%), and hematological improvement (HI) 7 (20%). The overall response rate was 48.6%. The median OS was 25 month (95%CI 13.8–36.1 mo). Conclusions: In this retrospective analysis, response to azacitidine in CMML was similar to response rates reported in other MDS patients on azacitidine studies. The median overall survival is comparable to AZA-001 randomized clinical study. Disclosures: Lancet: Celgene: Research Funding. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.

1726 Background: Treatment of CMML remains a clinical challenge, with no drug demonstrating clear clinical benefit. AZA yielded a survival benefit in higher risk MDS in a study that included few patients with CMML (AZA 001 trial, Lancet Oncol, 2009). Several small series of CMML treated by Decitabine (Wijermans, Leuk Res. 2008, Aribi A, Cancer. 2007 and Kantarjian H, Blood. 2007) and AZA (Scott, Br J Haematol. 2010) have been reported, but numbers were small with heterogeneous risk factors. Methods: A cohort of CMML pts (according to WHO classification) treated with AZA in 3 programs (French AZA compassionate program, Cleveland Clinic Foundation and H. Lee Moffitt Cancer Center) were reviewed. All pts received AZA for at least one cycle (75 mg/m2/d during 7 days every 28 d). Response was evaluated according to IWG 2006 criteria in patients with WBC <13G/L, but also took into account “proliferative” features of CMML (including palpable splenomegaly [SM] and white blood cell count [WBC] in patients with WBC > 13G/l), in agreement with our previous experience (Wattel, Blood 1996; Braun, Blood 2011 online). Results: Between 2004 and 2009, 79 CMML pts received AZA. The median age was 70 y (range 33–85), M/F: 50/29. Median interval from diagnosis to treatment was <6 months in 30 pts, 6–12 months in 10 pts and > 12 months in 34 pts. At onset of AZA, median WBC, Hb level and platelet count were 11.4 G/l (range 7–122), 10 g/dl (range 6.3–15.2) and 59 G/l (range 9–1214), respectively. According to the WHO classification, 53% were CMML1 and 47% CMML2. Forty six percent of pts had WBC > 13 G/l and 32% had palpable SM (44% pts had neither of those features, 32% pts had one and 23% had both). Among pts with WBC<13G/l, IPSS was low or int 1 in 24% pts and high or int 2 in 30%. Prior to AZA, 48% pts received previous therapy, including growth factors in 13%, hydroxyurea in 18% and intensive chemotherapy in 17% patients. Karyotype was normal (57%), with chromosome 5/7 abn (14%), and with other cytogenetic changes (29%). The median number of cycles of AZA administered was 6 (range 1–40). Thirty-four pts (43%) responded including CR (16%), PR (1.5%), marrow CR (8%), hematological improvement (HI) (18%). Among 60 pts who received more than 4 cycles, 33 (55%) responded, including 13 (22%) who achieved CR. Patients who achieved response were significantly older (median 71 vs 66 years in non responders, p=0.0170).WBC count (p=0.4241), WBC >13 G/L (p=0.483), Hb level (p= 0.4529), platelet count (p= 0.1658), marrow blast % (p=0.4278), palpable SM (p= 0.319), cytogenetics (p=0.947), disease duration (p= 0.808), prior therapy (p= 0.277) and prior therapy excluding GF (p= 0.147) had no impact on response. Twenty-six patients progressed to AML after a median of 630 d (range 85–1165 d), including 12/34 of the responders (6 CR, 1 PR and 5 HI). The median overall survival (OS) from initiation of AZA (OS) was 654 d. In univariate analysis, prior therapy when ESA were excluded (p=0.0488), palpable SM (median 420 d vs 870 d, p= 0.0230), WBC>13 G/l (420 vs 775, p= 0.0412), presence of palpable SM and/ or WBC>13G/l (none: median 876d vs either: 750d vs both: 401d, p= 0.0054) (figure 1) IPSS in pts with WBC<13 G/l (1085d for low /int1 vs 682 for high/ int2, p= 0.0046), marrow blast >10 % (383d vs 682d, p=0.028) significantly influenced OS while Karyotype (p=0.4217), sex (p= 0.5174) and Hb level had no influence on OS. By multivariate analysis, only marrow blasts>10 % (HR=2.19 (1.13–4.2), p=0.02) and presence of proliferative features (WBC>13G/L and/or palpable SM) (HR= 2.08 (.94 −4.6),p= 0.06) had prognostic value for OS. Finally, using a landmark analysis performed at 3 mo, Patients who achieved a response had a significantly better OS compared to patients who failed to respond (median 889 d vs 569 d, p= 0.047). Conclusion: In this population of CMML patients with generally poor prognostic features, the response rates (ORR 43%) and overall survival (21 mo) with AZA treatment was similar to that previously reported in higher risk MDS. No significant predictive factors for response to AZA were identified, but marrow blast % and proliferative features (including increased WBC count and/or splenomegaly) were adverse prognostic factors for survival. Disclosures: Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Membership on an entity's Board of Directors or advisory committees. List:Celegene: Consultancy. Fenaux:Celgene: Membership on an entity's Board of Directors or advisory committees. Komrokji:Celgene: Research Funding, Speakers Bureau.

4619 Background: Ofatumumab is a fully-humanized anti-CD20 monoclonal antibody approved in refractory CLL. The combination of high-dose methylprednisolone (HDMP) and anti-CD20 monoclonal antibody rituximab has previously shown positive results in high-risk refractory CLL. Herein we report our institutional experience with the combination of ofatumumab and HDMP for the treatment of patients with relapsed or refractory CLL. Methods: Between October 2009 and June 2011, 10 consecutive patients with relapsed or refractory CLL received HDMP and ofatumumab at Moffitt Cancer Center. HDMP was dosed at 1 g/m2 IV weekly for 3 weeks every 28 days for two cycles, then monthly for 3 cycles. Ofatumumab was administered according to package insert instructions along with prophylactic antimicrobials. The primary endpoint was to evaluate response as defined by the updated National Cancer Institute Working Group Guidelines (NCIWG 2008). Secondary objectives were to assess treatment tolerance and toxicity. Descriptive statistics were used for baseline characteristics and response rates. Results: Eight of ten patients were male, with a median age of 60 years (range 43–81). All patients were previously treated with rituximab, and were intolerant to or failed fludarabine and/or alemtuzumab. The median number of prior treatments was 3.5 (range 1–5). Seven patients had high-risk prognostic markers including unfavorable cytogenetics or unmutated IgVH. Six patients had 17p deletion, 2 patients had 11q deletion, and 3 patients had an unmutated IgVH (6 patients had two prognostic markers). Eight patients were able to complete all planned treatments. One patient discontinued treatment due to worsening performance status and 1 patient discontinued treatment due to progressive disease. HDMP and ofatumumab were used as a bridge to allogeneic hematopoietic stem cell transplant in 4 patients. Based on NCIWG 2008 criteria, 2 patients had a partial response (PR), 1 patient had progressive disease (PD), and 6 patients had stable disease (SD). Five patients with stable disease had a clinical decrease of lymph nodes or a decrease in lymphocyte counts. Despite the use of prophylactic antimicrobials severe infectious complications occurred in 40% of patients. Infections included 1 patient with norovirus, 1 patient with cytomegalovirus viremia and a fusarium infection of the neck, 1 patient with aspergillus pneumonia, Pseudomonas aeruginosa bacteremia, and an Escherichia coli bacteremia, and 1 patient with a necrotizing pneumonia. Conclusion: This data demonstrates the benefit of HDMP and ofatumumab combination in patients with heavily pretreated CLL. The combination of ofatumumab and HDMP has a role as salvage therapy and as a bridge to allogeneic stem cell transplant. The incidence of infection was high despite the use of prophylactic antibiotics. Aggressive antibiotic prophylaxis is warranted including coverage for mould infections. Disclosures: Off Label Use: Ofatumumab in combination with high dose methylprednisolone for the treatment of relapsed/ refractory CLL. Pinilla-Ibarz:GSK: Speakers Bureau.