ALBERT

Description: BACKGROUND: Patients with relapsed and/or refractory non-Hodgkin's lymphoma (NHL), especially those with aggressive lymphomas, have overall poor prognosis. Novel targets and therapies are under investigation. Molibresib (GSK525762) is a potent and specific inhibitor of the bromodomain and extraterminal domain (BET) family of proteins, the inhibition of which prevents transcriptional complex assembly and the subsequent expression of oncogenic drivers. Molibresib inhibits growth in NHL cell lines, both in vitro and in vivo. Study BET116183 was designed to evaluate the safety, tolerability, and preliminary efficacy of molibresib in relapsed and refractory hematologic malignancies. Here we report the results from the NHL dose escalation cohort. METHODS: Eligible subjects were adults with relapsed or refractory NHL. An accelerated dose titration was employed with one subject per dose level until the occurrence of a ≥Grade 2 drug-related toxicity; thereafter, subjects were enrolled in a standard 3+3 design. A Neuenschwander continual reassessment method (N-CRM) model was used to provide guidance for the next dose level. Dose escalation continued until the maximum tolerated dose (MTD) was identified. All data, including safety, tolerability, pharmacokinetics (PK), and efficacy, were used to identify the recommended part 2 dose (RP2D). RESULTS: From 14 May 2014 to the data cutoff date of 24 June 2018, 27 NHL subjects were enrolled and received at least one dose of study drug. Of these, 19 (70%) had B-cell lymphomas (diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma , and Burkitt's lymphoma); eight subjects (30%) had T-cell lymphomas (cutaneous T-cell lymphoma [CTCL], anaplastic T-cell lymphoma [ATCL], peripheral T-cell lymphoma, and adult T-cell leukemia/lymphoma). The median age was 64 years (range 24 to 76); 20 subjects (76%) were male and 7 subjects (24%) were female. The median number of prior treatments was 3 (range 1 to 〉 4). From the starting dose of 10 mg molibresib orally once daily (QD), the dose was escalated to 80 mg QD. The median time on study was 1.4 months (range 0.2 to 20 months). Two dose-limiting toxicities (DLTs) were identified in subjects treated at 60 mg QD, though one was subsequently determined not to be a DLT. One subject experienced Grade 4 thrombocytopenia related to study drug. A second subject experienced a Grade 2 mechanical fall; this event was later revised to unrelated to study drug. Across all dose levels, all subjects experienced an adverse event (AE); 25 subjects (93%) experienced at least one AE that was deemed to be related to molibresib treatment. The most common related AEs across all dose levels were thrombocytopenia (n = 21 [78%]), fatigue (n = 6 [22%]), nausea (n = 6 [22%]), diarrhea (n = 4 [15%]), and rash (n = 4 [15%]). Blood bilirubin was increased in 3 subjects (11%), and prothrombin time and activated partial thromboplastin time were prolonged in 2 subjects each (7%). Common Grade 3 and Grade 4 related events included thrombocytopenia (n = 19 [70%]), as well as anemia, asthenia, and increased blood bilirubin (n = 2 [7%] each). No Grade 5 related AEs were reported. Among all subjects, 11 (41%) required dose reduction for toxicity: 7 subjects at the 60 mg dose level (39% treated at that dose) and 4 at the 80 mg dose level (57% treated at that dose). PK analyses showed dose-proportionality after single and repeat dosing, with large variability between subjects. One subject with DLBCL achieved a complete remission that was durable through week 54 on study. Four additional subjects (one DLBCL and 3 CTCL) achieved partial remission, for an objective response rate (ORR) of 5/27 (18.5%). Five more subjects had stable disease as best response. Of six CTCL/ATCL subjects enrolled, three subjects had partial response for an ORR of 50% in this sub-population. CONCLUSIONS: This is the first study evaluating the safety and efficacy of the BET inhibitor molibresib in NHL subjects. Overall, thrombocytopenia and other AEs were monitorable, manageable and reversible. The RP2D was identified as 60 mg QD. Single-agent activity was observed across multiple NHL subtypes at both 60 mg and 80 mg doses; most notable was a 50% response rate in subjects with CTCL. Because of the promising data, Part 2 of the BET116183 study is currently open and enrolling subjects with CTCL to better define the clinical activity of BET bromodomain inhibition in this histology. Disclosures Dickinson: GSK: Consultancy. Kamdar:Genentech: Consultancy; Seattle Genetics: Speakers Bureau. Mateos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Alegre:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Kim:Roche: Research Funding; Mundipharma: Research Funding; J&J: Research Funding; Novartis: Research Funding; Kyowa-Kirin: Research Funding; Celltrion: Research Funding; Takeda: Research Funding. Martín:Janssen: Honoraria, Other: Travel expenses; Celgene: Consultancy, Honoraria, Other: Travel expenses; Roche: Consultancy, Honoraria, Other: Travel expenses; Servier: Honoraria, Other: Travel expenses. Horner:GSK: Employment. Winnberg:GSK: Employment. Mathew:GSK: Employment. Botbyl:GSK: Employment. Karpinich:GSK: Employment. Kremer:GSK: Employment. Dhar:GSK: Employment. Karadimitris:GSK: Research Funding; Gilead: Honoraria; Celgene: Research Funding.

Description: Background: EZH2 is the methyltransferase component of the polycomb repressive complex 2 (PRC2) that represses transcription of target genes via trimethylation of histone H3 at lysine 27 (H3K27me3), resulting in proliferative and migratory activity. EZH2 deregulation (via mutation or overexpression) in many cancers is associated with a more aggressive cancer phenotype and poor prognosis. GSK2816126, a highly selective and potent inhibitor of both wild type (wt) and mutant (mut) EZH2, decreases H3K27 tri-methylation, releases transcriptional repression of PRC2 target genes and induces anti-proliferative activity in several EZH2 wt/mut cancer cell lines. Methods: Part I of this 2-part study is a combined accelerated plus classic 3+3 with adaptive Bayesian design dose escalation of GSK2816126 in pts (≥18 years) with relapsed/refractory DLBCL, tFL, other NHL, MM and solid tumors. Primary objectives are to determine safety, tolerability and the recommended expansion dose. Secondary objectives include pharmacokinetic (PK) and pharmacodynamic (PD) analysis and preliminary evaluation of activity. Patients received two intravenous (IV) doses weekly for 3 weeks with one week off (3W-on/1W-off) in a 28 day cycle. Dose limiting toxicity (DLT) observation period for dose escalation was first 28 days. Results: As of 13 June 2016 data cut, a total of 30 pts have been treated with 50mg (n=2), 100mg (n=1), 200mg (n=1), 400mg (n=1), 800mg (n=3), 1200mg (n=4), 1800mg (n=10), 2400mg (n=5) and 3000mg (n=3) of GSK2816126 given IV twice weekly (3W-on/1W-off). Tumor types included 10 DLBCL, 2 tFL, 2 other NHL (FL and MZL) and 16 solid tumors. Preliminary results demonstrate GSK2816126 is well tolerated with no DLTs observed. Dose expansion is ongoing at 3000 mg IV (3W-on/1W-off). The most common drug-related adverse events (AEs) reported at 〉20% incidence were fatigue (53%), nausea (30%), anemia (20%) and vomiting (20%). PK was linear from 50mg to 3000mg given twice weekly, with moderate to high inter-subject variability and no accumulation. At 3000mg, Cmax was 22 ±34.1 ng/mL; t ½ 33.3 ±11.5 hour; AUC (0-∞) 109.8 ±53.5 ng*h/mL. Of 22 evaluable pts, 1 durable confirmed partial response (PR) was observed in an advanced GCB+ DLBCL patient (1800mg GSK2816126). 7 patients had stable disease, including an advanced FL patient with 45% tumor regression and a cholangiocarcinoma patient lasting 〉6 cycles. Conclusion: GSK2816126 is well tolerated with evidence of antitumor activity. Expansion of 3000 mg IV (3W-on/1W-off) is ongoing to confirm safety and efficacy. Part 2 of the study will enroll pts with EZH2 wt/mut GCB+ DLBCL and tFL, relapsed/refractory myeloma and solid tumors including castration-resistant and small cell prostate cancers. This study was funded by GSK. Disclosures Winter: Medivation: Other: Provision of investigational agent for clinical trial; GSK: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding. Ribrag:Gilead, Infifnity, Pharmamarr, BMS, Esai, Incyte, Nanostring: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding. Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Horner:GlaxoSmithKline: Employment. Carver:GSK: Employment. Pene Dumetrescu:GSK: Employment. He:GSK: Employment. McCabe:GSK: Employment. Creasy:GlaxoSmithKline: Employment. Dhar:GlaxoSmithKline: Employment. Carpenter:GSK: Employment. Johnson:Celldex Therapeutics: Research Funding.

Description: Abstract 3960 Introduction: The efficacy and safety of tositumomab and iodine I 131 tositumomab (TST/I-131-TST), the Bexxar® Therapeutic Regimen, were evaluated in 60 patients (pts) with chemotherapy-refractory low-grade (LG) or transformed B-cell non-Hodgkin's lymphoma (B-NHL) who had received at least 2 chemotherapy regimens and had either not responded to (72%) or had progressed within 6 months of their last regimen (28%) (J Clin Onc 2001; 19:3918 and Blood 2004; Abstract 2631). The primary efficacy endpoint was comparison of the number of pts who had a longer duration of response to TST/I-131-TST with the number of pts with a longer duration of response to their last qualifying chemotherapy (LQC). Thirty-nine (65%) pts, including 20% who attained a complete response (CR), responded to TST/I-131-TST, compared to 17 (28%) pts, including 3% CR, after their LQC (p

Description: Background: Bromodomains (BRDs) are domains found in a variety of proteins that recognize and bind to acetylated lysine residues in histone and other target proteins. The BRD and extra-terminal (BET) family of BRD-containing proteins bind to acetylated histone tails, alters chromatin structure and facilitates transcriptional complex localization to specific genes, thereby regulating gene transcription. The investigational agent GSK525762 is a potent small molecule inhibitor of the BET family of proteins that prevents assembly of macromolecular complexes and transcriptional response. GSK525762 inhibits growth in a broad spectrum of human hematological cancer cell lines, including cell lines derived from human patients with acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and multiple myeloma (MM). GSK525762 is orally bio-available and can cause tumor reduction and improved animal survival in in vivo xenograft models of hematologic malignancies. Methods: This is a Phase I/II, open-label, 2-part study. Part 1 is a dose-escalation phase to determine the safety, tolerability, and recommended Phase 2 dose (RP2D) of GSK525762 in adult subjects with relapsed/refractory AML, NHL, and MM. Dose escalation is performed independently for each of these three cohorts. An accelerated dose titration was employed with one subject per dose level until the occurrence of a ≥Grade 2 drug-related toxicity or dose-limiting toxicity; thereafter, subjects have been enrolled in a standard 3+3 design. A Neuenschwander continual reassessment method (N-CRM) model is used at each dose escalation decision to provide guidance for the next dose escalation level. Starting dose is 5 mg GSK525762 orally once daily and dose escalation continues until the MTD is identified. All data, including safety, tolerability, pharmacokinetics (PK), and efficacy, are used to identify the RP2D. In Part 1, approximately 60-70 subjects will be enrolled (approximately 20 in each of three disease-specific cohorts); no hypothesis is being tested, and all analysis will be descriptive and exploratory. In Part 2, the clinical activity of GSK525762 (overall response rate) will be evaluated in expansion cohorts of subjects with AML, NHL, and MM. Up to 32 subjects may be enrolled into the AML and NHL cohorts, and up to 37 subjects may be enrolled in the MM cohort. Cohorts may be closed early if they do not exceed futility assessment. In addition, an exploratory cohort of subjects with double-hit lymphoma (DHL) and triple-hit lymphoma (THL) will be enrolled to evaluate clinical activity in this patient population. Additional study objectives include analysis of PK after single and repeat dosing, evaluation of pharmacodynamics (PD) and the relationship between GSK525762 exposure and safety/efficacy/PD parameters. Recruitment is ongoing across five centers (USA, UK, and Australia). Currently, 40 subjects have been enrolled (29 AML, 8 NHL, and 3 with MM). Study funded by GSK. Disclosures Stein: Seattle Genetics: Research Funding; Agios Pharmaceuticals: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; Novartis: Consultancy. Huntly:Novartis: Speakers Bureau; BMS: Speakers Bureau; Ariad: Speakers Bureau; Pfizer: Speakers Bureau. Dickinson:GlaxoSmithKline: Consultancy, Research Funding. Horner:GlaxoSmithKline: Employment. Brennan:GlaxoSmithKline: Employment. Baron:GlaxoSmithKline: Employment. Kremer:GlaxoSmithKline: Employment, Equity Ownership. Dhar:GlaxoSmithKline: Employment.

Description: Abstract 4916 Introduction: The Bexxar® Therapeutic Regimen for relapsed/refractory follicular lymphoma (FL) is administered in 2 steps: a dosimetric dose and a therapeutic dose. Radioactive counts, obtained from sequential gamma camera scans of the whole body at several time points after the dosimetric dose, determine the patient (pt)-specific clearance (total body residence time, TBRT) and, along with pt body size, allow determination of the prescribed activity (PA) of the therapeutic dose. Pts do not receive the therapeutic dose if TBRT is outside 50 to 150 hrs and/or gamma camera images show altered biodistribution. TBRT is used to calculate the mCi of I-131 (PA) required to deliver the appropriate therapeutic dose of 65 or 75 cGy to the total body, depending on platelet count. Our aims were 1) to evaluate an alternative, inexpensive sodium iodide probe (probe) detector-based method of measuring radioactive counts for determination of TBRT and 2) to evaluate the clinical benefit of visually assessing gamma camera images for altered biodistribution. Methods: We retrospectively compared probe and gamma camera methods from a phase II study (RIT-II-001) and evaluated altered biodistribution assessed by gamma camera images from a post-marketing observational study. Forty-one of 47 FL pts enrolled in RIT-II-001 from December 1995 to November 1996 were included in the retrospective analysis of TBRT and PA. Pts received a median of 5 prior chemotherapies (range 2–13). Thirty of 41 (73%) pts had low-grade B-NHL, 90% had stage III or IV disease, 51% had bone marrow involvement, 88% had an International Prognostic Index score ≥ 2, and 16 of 34 (47%) pts had bulky disease 〉500 g. Dosimetry analysis was performed at 3 time points (Day 0; Day 2, 3, or 4; and Day 6 or 7) after dosimetric dose, as currently required for determining PA. The PAs of the therapeutic dose using TBRTs derived from probe and gamma camera counts were compared. Also, we retrospectively evaluated cases of altered biodistribution in an observational post-marketing study (BEX114606) of 2,649 pts who received a dosimetric dose from June 2003 to February 2010. Dosimetry and gamma camera images were independently reviewed from reported cases of altered biodistribution to evaluate the clinical benefit of visually assessing gamma camera images. Results: The mean TBRTs from the clinical study were 94.5 and 95.0 hrs from the probe and gamma camera methods, respectively, and individual TBRTs were highly correlated (r = 0.98). The mean PAs of the therapeutic dose, derived from probe and gamma camera TBRTs, were 85.8 mCi and 85.3 mCi, respectively. The point estimate for the ratio of the PA was 0.995 and the 90% CI (0.984, 1.006) was well within the typical range of 0.80 to 1.25 for demonstrating bioequivalence. The observational study found that only 5 of 2,649 (0.2%) pts did not receive the therapeutic dose due to suspected altered biodistribution. Dosimetry data and gamma camera images were available for 3 pts. Independent review confirmed that all 3 pts had accurately determined TBRTs, but only 1 pt had confirmed altered biodistribution by visual assessment of gamma camera images and TBRTs. Conclusion: TBRTs derived from probe and gamma camera counts were highly comparable. Thus, the probe and gamma camera methods to determine TBRT and calculate the PA of the therapeutic dose of Bexxar appear equivalent. Altered biodistribution prevented only 5 of 2,649 (0.2%) pts from receiving the therapeutic dose of Bexxar. Only 1 pt (0.04%) was independently confirmed to have altered biodistribution by visual assessment of gamma camera images, consistent with the TBRT. Therefore, visual assessment of gamma camera images added no benefit beyond TBRT in determining whether to administer the therapeutic dose of Bexxar. These data indicate that either sequential probe or gamma camera-based dosimetry is sufficient for determining whether to administer the therapeutic dose, and that visual assessment of gamma camera images does not appear to be necessary to detect the rare instance of an altered biodistribution. Disclosures: Horner: GlaxoSmithKline: Employment. Off Label Use: The BEXXAR therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) is indicated for the treatment of patients with CD20 antigen-expressing relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin's lymphoma. Siegel: GlaxoSmithKline: Consultancy. Jewell: GlaxoSmithKline: Employment. Lunger: GE Healthcare: Employment. Young: GlaxoSmithKline: Employment. Wynne: GlaxoSmithKline: Employment. Williams: GlaxoSmithKline: Employment. Lin: GlaxoSmithKline: Employment. Kaminski: GlaxoSmithKline: Patents & Royalties, Research Funding. Wahl: GlaxoSmithKline: Consultancy, Patents & Royalties; Nihon Medi Physics: Consultancy; Spectrum Pharmaceuticals: Consultancy; Naviscan PET systems: Consultancy; Threshold Pharmaceuticals: Equity Ownership. Vleisides: GlaxoSmithKline: Employment.

Description: Background Bromodomain and extra-terminal domain proteins are promising epigenetic anticancer drug targets. This first-in-human study evaluated the safety, recommended phase II dose, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the bromodomain and extra-terminal domain inhibitor molibresib (GSK525762) in patients with nuclear protein in testis (NUT) carcinoma (NC) and other solid tumors. Methods This was a phase I and II, open-label, dose-escalation study. Molibresib was administered orally once daily. Single-patient dose escalation (from 2 mg/d) was conducted until the first instance of grade 2 or higher drug-related toxicity, followed by a 3 + 3 design. Pharmacokinetic parameters were obtained during weeks 1 and 3. Circulating monocyte chemoattractant protein-1 levels were measured as a pharmacodynamic biomarker. Results Sixty-five patients received molibresib. During dose escalation, 11% experienced dose-limiting toxicities, including six instances of grade 4 thrombocytopenia, all with molibresib 60–100 mg. The most frequent treatment-related adverse events of any grade were thrombocytopenia (51%) and gastrointestinal events, including nausea, vomiting, diarrhea, decreased appetite, and dysgeusia (22%–42%), anemia (22%), and fatigue (20%). Molibresib demonstrated an acceptable safety profile up to 100 mg; 80 mg once daily was selected as the recommended phase II dose. Following single and repeat dosing, molibresib showed rapid absorption and elimination (maximum plasma concentration: 2 hours; t1/2: 3–7 hours). Dose-dependent reductions in circulating monocyte chemoattractant protein-1 levels were observed. Among 19 patients with NC, four achieved either confirmed or unconfirmed partial response, eight had stable disease as best response, and four were progression-free for more than 6 months. Conclusions Once-daily molibresib was tolerated at doses demonstrating target engagement. Preliminary data indicate proof-of-concept in NC.

Description: Abstract 2732 Poster Board II-708 PURPOSE: Patients with indolent lymphoma generally require a number of therapies to address the relapsing course of disease and it is therefore important to provide long-term safety and efficacy data for novel therapeutics. We evaluated such data from the original phase II trial of the tositumomab and iodine-131 tositumomab therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab METHODS: From July 1998 to November 1999, 40 patients with a median age of 57 years (24 rituximab nonresponders: 11 with response 7 cm and 20 patients (50%) had tumor masses 〉5 cm. The median number of prior treatments was 4 (range 1–11); 59% of patients were chemotherapy-resistant. Histology included follicular grade 1–2 (26), grade 3 (2), other indolent (2), and transformed (10). After 2 years on study or after disease progression, long term follow-up was conducted every 6 months for 10 years with CT and laboratory studies. This report presents an update, with investigator-assessed tumor evaluation, from the J Clin Oncol 23:712, 2005. RESULTS: The median duration of follow-up from the dosimetric dose was 54 (range 1–119) months. The overall response rate was 72% (28 of 39 evaluable patients with 9 complete responders). The median duration of overall response was 18.9 months; the proportion of patients maintaining response at 5 years is estimated at 40% with just two known relapses after two years. Five of 9 complete responders have been continuously maintained. For all 40 study patients, the median progression-free survival (PFS) was 10.4 months (95% CI: 5.7, 18.6) and the estimated 5 year PFS is 28%. The estimated median overall survival for all patients is 80.0 months. To date, 20 deaths have been reported, 10 without documented disease progression. Six second cancers have occurred: 2 acute leukemia, 1 prostate, 2 skin (1 squamous, 1 Merkel cell) and 1 primary hepatic. The incidence of secondary leukemia remains the same as previously reported in 2005 at 5% (2 of 40 patients). Seven of the 40 patients enrolled in this study had elevated thyroid stimulating hormone (TSH) levels prior to receiving the therapeutic dose of iodine-131 tositumomab and 2 patients did not have baseline TSH data. Of the 31 patients with normal baseline TSH levels prior to treatment, 3 developed elevated TSH as of July 2009 and as reported previously (J Clin Oncol 23:712, 2005). There were no cases of hypothyroidism reported as an adverse event by investigators as of July 2009. CONCLUSIONS: The group of extensively pretreated (median = 4) patients participating in this phase II study survived a median of 6.7 years after receiving the BEXXAR® therapeutic regimen. No additional cases of leukemia were seen and no unexpected toxicities were observed. Of the 72% of patients responding to treatment, about 40% were estimated to continue their response at 5 years, including 5 of 9 complete responders. These data demonstrate durable efficacy of BEXXAR® in an indolent lymphoma population with disease progression after rituximab. Disclosures: Horning: GlaxoSmithKline: Honoraria, Research Funding. Podoloff:GE Healthcare: Honoraria, Research Funding. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Vleisides:GlaxoSmithKline: Employment.

Description: Abstract 3759 Poster Board III-695 Purpose Tositumomab and iodine I 131 tositumomab (Bexxar® Therapeutic Regimen) has been found effective in relapsed/refractory follicular lymphoma. We now report updated results of a single center, single-arm, Phase II trial of a single one-week course of this treatment for 76 previously untreated, stage III and IV, follicular lymphoma patients (reporting period June 1996 to May 2009). Patients and Methods Patients had a median age of 49 years (range 23 to 69) and received a dosimetric dose followed by a single total body dose of 75 cGy iodine I-131 tositumomab one week later. Seventy percent had stage IV disease and 70% of patients had histological grade 1 follicular lymphoma, 29% had grade 2, and 1 patient had mantle-cell lymphoma. Bone marrow involvement was present in 64% of patients; 43% of patients had at least one tumor 3 5 cm in diameter; LDH was elevated in 30%. Overall, 35% of patients had high risk Follicular Lymphoma International Prognostic Index (FLIPI) scores and 50% had intermediate risk scores. Patients entered long-term follow-up after disease progression or after 2 years on study. Response, second malignancy occurrence and thyroid medication use were assessed every 6 months for 5 years and yearly thereafter up to 12 years post treatment. Results As previously reported (NEJM 352:441, 2005), the overall response rate was 97% with 57 patients (75%) achieving a complete remission. Hematologic toxicity, although common, was modest to moderate (grade 4 neutropenia in 5% of patients and no grade 4 thrombocytopenia). After a median of 10 years follow-up (range 0.7 to 12.3 years), the median duration of response was 6 years (95% CI: 2.5, 10.8), with approximately 40% remaining progression-free at 10 years. For the 57 complete responders, median progression-free survival was 10.9 years (95% CI: 8.3, NR). Ten-year overall survival was approximately 82%. Five cases (7%) of hypothyroidism occurred 0.5 to 2.9 years after treatment and were managed with thyroid hormone replacement. Eleven patients (14%) were diagnosed with second malignancies including 4 skin neoplasms (2 basal cell and 2 squamous cell) and 7 visceral neoplasms (3 breast, 2 prostate, 1 endometrial cancer, 1 glioblastoma). One case of myelodsyplastic syndrome was diagnosed about 8 years after treatment. Conclusion A single course of treatment with Bexxar therapeutic regimen can commonly produce durable responses, especially durable complete responses lasting over a decade in patients with untreated follicular lymphoma. Further studies comparing this monotherapy to other regimens, including combination therapies, are warranted. Disclosures: Kaminski: GlaxoSmithKline: Honoraria, Patents & Royalties, Research Funding, Speakers Bureau. Off Label Use: Radioimmunotherapeutic for treatment of frontline treatment of follicular lymphoma. On-label use is for relapsed/refractory patients. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Vleisides:GlaxoSmithKline: Employment. Wahl:Nordion: Honoraria; GlaxoSmithKline: Patents & Royalties.