ALBERT

Description: The treatment of ARL is complicated by the numerous immuno-chemotherapy, antiretroviral, and prophylactic options available to lymphoma specialists. The optimal management in the era of combination antiretroviral therapy (cART) is unclear. We administered a survey instrument to determine physician preferences and perceptions in the management of ARL and to assess the variability in treatment in Canada. The survey was developed with items grouped into key domains of ARL management (physician demographics, attitudes, and treatment preferences) and piloted for content validity and clarity. The final questionnaire was administered to lymphoma physicians with valid contact information in the provinces of Ontario (ON; n=155) and British Columbia (BC; n=48). The Dillman Tailored Design Method was followed for multi-modality (internet and standard mail) survey administration. Of 196 physicians, 131 either responded by completing the questionnaire (n=117; 60% response rate) or declining to participate (n=14; 7%). Most responders were male (63%), white (70%), practicing in an academic setting (63%), and belonged to a median age group range of 41–50 years. The majority (98%) had a positive attitude towards the treatment of ARL, as measured by a previously validated 2-item attitude scale. However, barriers to adequate care were still identified; 84% of physicians agreed that uncontrolled human immunodeficiency virus infection represented a major barrier to ARL care and 54% agreed that a patient’s concurrent intravenous drug abuse impaired care. Most physicians recommended the concomitant use of cART in the care of their patients with ARL (n=72 of 109 responses; 66%). Similarly, a majority of respondents recommended CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone; n=92 of 108 responses; 85%) to form the backbone of chemotherapy. The addition of the rituximab was preferred by 41% physicians but not by 40% others, with remaining respondents unsure of the agent’s role. In logistic regression analysis, use of rituximab was predicted only by location of practice (province), after adjusting for other potential predictors including physician age, race, gender, practice environment (academic vs. community), years of experience, ARL patient volume, and modality of survey response. Physicians from BC were much more likely to administer rituximab than ON practitioners (OR 44.5; 95% CI: 7.76–255.0, p

Description: Introduction: Sezary syndrome is a rare, aggressive and advanced stage of cutaneous T cell lymphoma where patients exhibit total body erythroderma and peripheral blood involvement. Patients can progress from preexisting mycoses fungoides or present de-novo. Historically median survival has been less than two years however with current combinations of skin directed and immunomodulatory therapy median survival has been documented up to 3–4 years, however randomized trials are lacking given the rarity of this disorder. We describe the outcomes 23 patients followed in our centre diagnosed with sezary syndrome based on peripheral blood involvement and erythroderma who have been treated primarily with combination skin and immunomodulatory therapy. Methods: A review of all patients diagnosed with sezary syndrome in our centre was conducted. Base line characteristics, survival, number and type of therapies as well as responses to treatments were recorded Results: 23 patients were identified. 11 male, 12 female, average age at diagnosis 64.7 yrs (range 47–85). Therapies included total skin electron beam (TSEB), PUVA, Interferon, oral retinoids, and extracorporeal photophoresis (ECP). 5 patients had received prior traditional chemotherapy including CHOP, chlorambucil and purine analogues with either no or transient responses. 19 patients received a combination of all 5 therapies. 19 patients received IFN, 13 TSEB, 21 PUVA, 18 ECP and 16 oral retinoids. 7 patients received 3 or fewer therapies (3 in process of escalating therapy, 1 CR to TSEB, 3 pts refused multiagent therapy as elderly and stable on PUVA +/− retinoids). 6 patients achieved a durable complete remission while on therapy (4 received IFN/TSEB/PUVA/ECP, 1 IFN/PUVA/ECP, 1 TSEB alone), 3 patients had progressive disease, and the remainder either had partial responses or stable disease. Median follow-up was 44 months (range 9–127). Median survival of the entire cohort was 37 months (mean 52 months, range 6–108 months, 5 patients have been diagnosed in the last 12 months). There have been 5 deaths to date, median 43 months (range 33–101) from the time of diagnosis. Cause of death included 2 cardiac, 1 renal, 1 infection, and 1 progressive disease. There was no correlation between survival and LDH at presentation, sezary cell count or number of therapies. There was a modest correlation between survival and age at diagnosis (R2=0.1263). Patients who received TSEB had an average of 57 months survival vs. 33.5 months than those who did not, however this was not statistically significant. Reasons not to receive TSEB included 5 patient refusal, 3 still escalating therapy, 2 had adequate response to other therapies. Patients who achieved a CR to therapy had a median survival of 63 months (average 65 months) vs. those who did not achieve a CR had a median survival of 22 months (average 65 months). Conclusions: Patients receiving combination immunotherapy and skin based treatments for sezary syndrome appear to be living longer than historical series. Given the small number of this cohort it was not possible to statistically determine variables predictive of prolonged survival, however patients who received TSEB and or achieved a CR to treatment had median survival of approximately 5 years. The majority of patients received maintenance immunotherapy to sustain disease control.

Description: Introduction: Nearly one in five cancer survivors report limitations in ability to work following diagnosis, with poor work-related outcomes particularly noted in the hematologic cancers. Although much is known about the efficacy, toxicity and direct costs of treatment for follicular lymphoma, there is no data assessing the impact of this diagnosis on productivity of affected individuals. Methods: We conducted a consecutive cross-sectional study of patients attending a malignant hematology clinic at a large multi-disciplinary cancer centre. Patients with a diagnosis of FL or other indolent NHL were asked to complete questionnaires assessing demographics, health status (EQ-5D), and work productivity and activity impairment (WPAI questionnaire). Results: Eighty-four patients completed the survey study (〉95% response rate). Mean age was 58.7 (+/−13.8 SD) and 55% were male. Diagnoses included FL (55%), CLL (25%), and other indolent NHL (20%). The majority of patients presented in advanced stage (stage III–IV; 65%) and had received some therapy, although 29% were still being observed without having received therapy by the time of survey administration. The median disclosed income was $40,000–$59,000; 76% had pursued post-secondary education. Over 61% were working full-time prior to diagnosis while 14% were retired. Patients reported a minimal impact on their work productivity (1.9+/−3.2 on a scale of 0 to 10; 0=no effect and 10=complete impairment of activity) and on their daily activities (2.4+/−3.1) attributable to their cancer diagnosis. However, following diagnosis of NHL (and at the time of survey completion), only 33% were able to continue full-time work, 7% were working part-time, 10% required disability, and 37% were retired. Of those still working, a mean of 2.1 days (+/−6.9) were missed due to illness in the preceding 4 weeks, with a mean of 16 days (+/−8.7) worked in that period. Only 6% received paid assistance, while 17% required unpaid care from a partner/spouse, relative, or friend. Unpaid caregivers missed a mean of 11.3 days (+/−16.2) of work and provided a mean of 9.8 days (+/−13.4) of care. There was a significant inverse correlation between daily activity scores (high values=complete impairment) and health status ratings (high values=excellent health status/utilities) ascertained by the EQ-5D instrument (Spearman correlation coefficient −0.69; p5) was predicted by poor self-rated health status (OR 32.1; 95% CI 5.9–174.2; p

Description: Abstract 1916 Poster Board I-939 Introduction: Since the introduction of combination antiretroviral therapy (cART), the incidence rates of non-Hodgkin's lymphoma (NHL) and primary central nervous system lymphoma (PCNSL) have declined; however, less is known about the rates of other hematologic malignancies such as Hodgkin lymphoma (HL) and multiple myeloma (MM). We aimed to study changes in the incidence and outcomes of hematologic malignancies (HMs) in the pre- and post-cART eras. Methods: A retrospective analysis of The Ontario HIV Treatment Network Cohort Study (OCS) was performed. The OCS is an ongoing prospective study of HIV-infected adults from 11 sites throughout Ontario, Canada. Incidence rates of HMs were calculated for the pre- (

Description: Background: The outcome of peripheral T-cell lymphomas (PTCLs) remains poor and improved therapies are needed. Retrospective data suggest that integration of anthracyclines in the primary therapy may not impact outcome, providing the rationale to explore alternative regimens. Histone deacetylase inhibitors appear to have a class effect in PTCLs andromidepsin monotherapy demonstrates activity in a proportion of patients with relapsed/refractory PTCLs and can induce durable remissions. Gemcitabine is reported to be a highly active agent in PTCL, and the GDP (gemcitabine, dexamethasone, cisplatin) regimen has become a standard chemotherapy backbone for relapsed aggressive lymphomas (Crump, JCO 2014). We investigated the feasibility, safety and efficacy of GDP combined with romidepsin in a phase I dose escalation trial. Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) were also included. Methods: Patients with relapsed/refractory PTCL or DLBCL, PS 0-2, with measurable disease and who had received one or two prior lines of systemic therapy, were treated with standard doses of GDP (gemcitabine, 1000 mg/m2 d1, d8; dexamethasone, 40 mg po d1-4; cisplatin, 75 mg/m2 d1) every 21 days, plus escalating doses of romidepsin (6, 8, 10 and 12 mg/m2) on days 1 and 8 to a maximum of 6 cycles in a standard 3+3 design. After the first 4 patients were enrolled, based on the observed pattern of thrombocytopenia, the treatment schedule was modified so that gemcitabine and romidepsin were given on days 1 and 15 and cycles extended to every 28 days. Dose-limiting toxicities (DLTs) were assessed during the first 2 cycles and defined as requiring platelet transfusion for bleeding, grade 3 hematological toxicity lasting 〉10 days, grade 4 hematological toxicity lasting 〉7 days, febrile neutropenia, or grade 3-4 non-hematological toxicity attributable to romidepsin. Responses were as per Cheson, JCO 2007 excluding PET scans. Results: 20 eligible patients (PTCL n=10; DLBCL n=10) were enrolled between 10/2013 and 01/2016 and treated with GDP plus romidepsin. The main PTCL subtype was PTCL, not otherwise specified (50%). Median age was 65 years (24-74); 9 were female; ECOG performance status was 0 (n=2), 1 (n=13), or 2 (n=5). Number of prior therapies was 1 (n=17) or 2 (n=3). 17 (85%) patients received 〉90% of the planned dose each cycle. The median number of cycles was 2 (range, 1-6); one patient is still on therapy. The reasons for treatment discontinuation were lymphoma progression (n=10), toxicity (n=2), proceeding to autologous stem cell transplant (ASCT, n=3), intercurrent illness (n=1), or completion of 6 cycles (n=3). On the 21-day schedule at 6 mg/m2 romidepsin, there were 3 DLTs among four patients (2 with grade 3-4 thrombocytopenia, 1 venous thromboembolic event). On the 28-day schedule, there were no DLTs observed in the three patients treated at each of the 6, 8 or 10 mg/m2 dose levels. At 12 mg/m2 there were 4 observed grade 3 DLTs among six evaluable patients (hypotension, acute kidney injury, anorexia, thrombocytopenia 〉10 days). Notable toxicities during any cycle were: febrile neutropenia (n=2); grade 3-4 thrombocytopenia (n=9); grade 3-4 neutropenia (n=4); and grade 3-4 anemia (n=4); grade 2 atrial fibrillation (n=2); grade 2 QTc prolongation (n=1); grade 1 sinus tachycardia (n=1); grade 2-3 infections (n=16); grade 1-3 cutaneous toxicity (n=9); grade 1-3 thromboembolic events (n=2); TIA (n=2) or stroke (n=1). One patient died after cycle 1 due to sepsis. 7 other patients have died of progressive lymphoma. The overall response rate was 9/20 (45%), all were partial remissions (PR), 3 had stable disease (SD), 4 had progressive disease (PD), and 4 were not objectively evaluable. Of the responders, 5 had PTCL and 4 had DLBCL. Four patients went on to ASCT. With a median follow-up of 5.8 months, the median duration of response was 2.8 months and median PFS is 2.2 months. For all patients, the 1 year PFS was 6% and 1 year OS was 43% Discussion: Full doses of GDP can be combined with a recommended phase II romidepsin dose of 10 mg/m2 given on a day 1, 15 every 28 days schedule. Thrombocytopenia prohibits this combination on a 21-day schedule. Toxicity is otherwise acceptable and as expected. Further study at the recommended dose and schedule would be required to properly define the activity of this regimen in PTCLs and DLBCL. Disclosures Reiman: Celgene: Honoraria, Research Funding. Buckstein:Novartis: Honoraria; Celgene: Honoraria, Research Funding. Kuruvilla:Merck & Co., Inc.: Consultancy, Honoraria. Villa:Lundbeck: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria. Hay:Amgen: Research Funding; Novartis: Research Funding; Janssen: Research Funding; Kite Pharmaceuticals: Research Funding.

Description: With increasingly effective therapy for patients with aggressive histology non-Hodgkin’s Lymphoma and Hodgkin’s Lymphoma, more patients are attaining complete remission and are eligible for follow-up monitoring. Such monitoring offers the potential for early detection of relapse and surveillance for late effects of treatment, but is resource-intensive and may lead to unnecessary investigation of false relapses and cumulative radiation exposure. A number of Practice Guidelines (PG) provide recommendations on follow-up of patients with lymphoma, but provide conflicting recommendations particularly relating to the use of imaging. The PG of the American College of Radiology (ACR) and the National Comprehensive Cancer Network (NCCN) recommend routine use of imaging in follow-up, while those of the Canadian Association of Radiologists (CAR) and Cancer Care Ontario (CCO) recommend limiting imaging to patients suspected of relapse and those at higher risk of recurrence. We conducted a survey of practicing hematologists across Canada to document follow-up practice of patients outside of clinical trials. A 12-question survey was mailed to 244 Hematologists identified from the database of the Royal College of Physicians and Surgeons of Canada. The Dillman method was used to administer the questionnaire with a second mailing sent at 4 weeks to non-respondents. The target response rate was 50%. 127 responded (52%) after the second mailing. 93% indicated that they routinely follow-up patients in remission following curative treatment. 41% reported following patients indefinitely, 39% followed patients for up to 5 years, and 22% tailored the duration to the risk of relapse (generally 2–5 years). The median visit interval in years 1–2 was 3 months, years 3–5 6 months, and beyond 5 years 12 months. 41% used imaging (generally CT scans) routinely in all patients, while 31% used scans only in patients in partial remission and 21% in patients felt to be high risk at presentation. The majority of respondents performed CBC and LDH blood testing routinely in all patients and performed serum TSH levels in patients following mediastinal radiation. Serum electrolytes, liver function testing and blood films were ordered routinely only by a minority of respondents. 27% of practitioners reported utilizing printed educational material for patients and/or primary care practitioners regarding follow-up. 25% indicated an intent to change their follow-up practice in the near future, generally citing a plan to limit the duration of follow-up and to decrease reliance on CT scanning. Conclusion: This national survey indicates that the majority of Canadian hematologists routinely follow patients with lymphoma after curative treatment. The use of imaging in follow-up is variable, but is more consistent with the recommendations of the CAR and CCO than the ACR and NCCN.

Description: Introduction: Health utilities (HU) elicited directly from patients have immediate application in facilitating medical decision-making and cost-effectiveness determinations. Collection of HU using generic health status scales enable comparisons across diseases, but may not be sensitive to variations in health states within a particular disease. The EuroQOL EQ5D is a generic scale that has never been used to generate utilities in a broad spectrum of follicular/indolent lymphoma patients and has not been validated in this context. Methods: A consecutive, cross-sectional cohort of patients attending an outpatient malignant hematology clinic at a major cancer centre (Toronto, Canada) represented the eligible study population. Patients with a diagnosis of FL or other indolent NHL who consented to the study were asked to complete demographic and disease specific questionnaires in addition to the EuroQOL EQ-5D and Functional Assessment of Cancer Therapy (FACT)-Lymphoma quality of life assessment tools. Results: Eighty-four patients completed the survey study (〉95% response rate). Mean age was 58.7 (+/− 13.8 SD) and 55% were male. Diagnoses included FL (55%), CLL (25%), and other indolent NHL (20%). The majority of patients presented in advanced stage (stage III–IV; 65%) and had received some therapy to date, although 29% were still being observed at the time of survey administration. The mean utility score for the population was 0.84 (+/− 0.24; range 0–1). We evaluated the construct that patients receiving active treatment and those who were not in remission would have lower utility scores. Indeed, utilities were higher in patients being observed (0.91 +/− 0.16) compared to those in first remission (0.84 +/− 0.25), subsequent remissions (0.81 +/− 0.20), or those who were receiving active chemotherapy (0.75 +/− 0.27; p=0.049). Patients who were being followed in ongoing remission also trended to higher health status values (mean 0.88 +/− 0.21) compared to those who were not in remission (0.80 +/− 0.22; p=0.15). Utilities elicited from the EQ5D showed a moderate correlation with a criterion measure of quality of life, the FACT-Lymphoma scale (Spearman correlation coefficient 0.54, p

Description: Abstract 3681 Introduction: The First-Line Indolent Trial (FIT) demonstrated that administration of a single infusion of 90Y-RIT to follicular lymphoma grade 1 or 2 patients with CR or PR after induction chemotherapy could significantly prolong time to progression versus no further therapy. [JCO 2008;26(32):5156–63]. Recently, Fowler et al (ASH 2011, abstract 99) have reported on a chemoimmunotherapy approach followed by both RIT consolidation and rituximab maintenance for advanced stage FL patients with FLIPI risk factors 〉2. However, molecular status (PCR for t[14;18]) was not reported beyond one year of follow-up. We report a phase II study of safety and efficacy of 90Y-RIT following R-CHOP chemotherapy in patients with FLIPI=2–5, advanced stage FL. Maintenance rituximab is given every 3 months (m) post 90Y-RIT, for 24 m. Planned accrual is 33 evaluable patients with extensive two year molecular and immunologic follow-up. Novel insights into the biologic and immunologic effects of this combination regimen are presented. The primary endpoint of our study is the final complete response (CR) rate, defined according to the Cheson criteria and measured 3 m after day 1 of the 90Y-RIT therapy. Secondary outcomes included molecular remission and immunologic effects. Methods: In patients who had PCR detectable t[14;18] in baseline diagnostic specimens, quantitative real-time PCR was performed on blood and available bone marrow, at baseline, post 6xR-CHOP and Q 3 months post 90Y-RIT treatment for 24 m. The sensitivity of our PCR assay was 1 in 105cells. Flow cytometry for % B cell clonality was performed at the same time points. T and B cell counts, Ig levels and vaccine serology have been recorded pre and post treatment. Results: We have enrolled 26 patients with a median age of 54 yrs, 80% stage 4, 58%, intermediate FLIPI=2, 42% high FLIPI=3–5. Sixteen of 26 [62%] patients had a complete response (CR/CRu) to R-CHOP and the remaining 10 [40%] showed partial response (PR). One patient died due to sepsis prior to 90Y-RIT. Five patients with a partial response post R-CHOP converted to CRu post 90Y-RIT. A total of 19 of 24 (79%) patients who received 90Y-RIT, achieved CR/Cru. Post 90Y-RIT, three patients have relapsed. One other developed a secondary malignancy by 9m. The treatment has been most favourable for patients with FLIPI=2, where 13/14 (93%) remain progression-free [median follow-up= 32 m, range= 12.5–62 m]. There were no SAEs attributable to the 90Y-RIT treatment. Seventeen patients had PCR detectable t(14:18) translocations. Quantitative PCR measurements were concordant with flow cytometry. Of these, 16, were evaluated post 90Y-RIT and 15/16 (94%) of these patients became PCR negative in blood. Post 90Y-RIT, 2 patients showed increase in PCR levels and relapsed clinically. All remaining pts with PCR markers are PCR negative in blood as far as 24 m post 90Y-RIT. CD3+T cell counts remained normal, but CD19+B cells fell below the 1% detection level by flow cytometry during the two yrs of maintenance therapy post 90Y-RIT. Interestingly, mean IgG levels remained close to normal, but mean IgM levels fell below normal. Memory immune responses to measles and mumps were maintained post chemo-radiotherapy. Antibody titres to Rubella did not change significantly post 90Y-RIT. No HAMA response has been detected in any of the patients. Conclusions: We found effective eradication of follicular lymphoma from the blood and bone marrow of the high risk lymphoma pts with 2 or more FLIPI risk factors with first line treatment of 6xRCHOP and all but one of our evaluable patients (94%) achieved molecular remission in blood post 90Y-RIT. Molecular remission was sustained after 90Y-RIT up to 2 years, considerably longer than that reported by Fowler et al (ASH 2011, abstract 99). Longer follow-up with annual monitoring is planned to determine the precise response duration. The progression-free survival rates are similar or more favourable to previous reports [Blood 2006;108:1504–1508, J Clin Exp Hem. 2012; 52,no. 1]. IgG levels remain close to normal indicating that memory B cells are intact and this was consistent with no significant change in titres to common previously vaccinated pathogens such as rubella. The significance of persistent reductions on IgM levels is unclear. Acknowledgments: This study was sponsored by Bayer Canada and Spectrum Pharmaceuticals. Disclosures: Berinstein: Spectrum Pharma: Clinical Advisory Board Other. Off Label Use: Zevalin for first line treatment of aggressive follicular lymphoma.

Description: Abstract 745 Background: The optimum chemotherapy combination prior to autologous stem cell transplantation (ASCT) for patients with relapsed or refractory aggressive non-Hodgkin lymphomas (NHL) has not been defined. We previously established the safety and efficacy of outpatient treatment with GDP in a phase II study (Crump et al, Cancer 2004) leading to this phase III trial testing the hypothesis that GDP is as effective and less toxic than standard DHAP, and potentially associated with better quality of life (QoL) and less resource utilization. Methods: Patients (pts) with relapsed/refractory aggressive NHL were stratified by IPI score at relapse (0, 1 vs 2,vs 〉=3 risk factors), immunophenotype (B vs T cell), disease status following initial treatment (response duration 〈 1yr vs duration 〉 1yr vs no response/PD) and prior treatment with rituximab (R); and were randomized to 2–3 21-day cycles of G 1000 mg/m2 day 1 & 8, D 40 mg day 1–4, P 75 mg/m2day 1 or standard DHAP. Pts with CR, PR (or SD, per institutional policy) proceeded to PBSC collection and ASCT. The protocol was amended 11/2005 to include R with GDP or DHAP for pts with CD20+ lymphoma. Co-primary endpoints were response rate (RR) after 2 cycles (CR/CRu/PR) according to 1999 International Workshop criteria, and transplantation rate; FDG-PET was not used to determine response. Using a non-inferiority design, the study was powered to exclude a 10% difference in RR between GDP and DHAP (α 0.05, power 80%). Other endpoints included toxicity, event-free (EFS) and overall survival (OS), QoL and an economic analysis. FACT-G, FACT-CNS and FACT-LYM instruments and validated lymphoma-specific questions were used to assess QoL. Results of a second randomization to post-ASCT rituximab consolidation vs observation for pts with CD20+ lymphoma will be reported subsequently. Results: From 8/2003 to 11/2011, 619 pts were enrolled at 52 centres in Canada, Italy, Australia and the US (GDP 310 DHAP 309). Pt characteristics: median age 55 yrs (28.4% 〉60 y); histology: DLBCL 71%, PTCL 4%, ALCL 4%, transformed 14%; IPI risk factors: 0,1: 38%, 2: 29%; 〉3: 33%; elevated LDH 59%; prior R treatment 67%; refractory to initial therapy 31%; all baseline characteristics were balanced between treatment arms. In the intention to treat (ITT) population, RR for GDP was 45.2% and for DHAP 44.0%. The upper boundary of the one-sided 95.6% confidence interval for the difference in RRs was 5.67% and did not cross the pre-specified 10% non-inferiority boundary, meaning protocol-stated criteria for declaring GDP non-inferior to DHAP were met (p=0.005); results were robust when assessed using a per-protocol analysis. 362/554 pts (65.3%) with B cell NHL received R with protocol therapy: RRs were similar between arms in pts with and without prior R exposure, and with and without R added to GDP or DHAP. The transplantation rate was 51.8% for GDP vs 49.3% for DHAP (per protocol analysis; p = 0.49); 6 pts in each arm could not mobilize adequate PBSCs. At a median follow-up of 53 months, 4 year EFS was 25.6% and 26.1% (HR 0.99, p=0.95) and 4 year OS 39.0% and 39.1% (HR 1.03, p=0.78) for GDP and DHAP, respectively. Pts receiving GDP experienced less grade 3–4 toxicity (47 vs 61%, p=0.0003), including febrile neutropenia (9 vs 23%, p

Description: Background: Although the natural history of follicular lymphoma is indolent with a median overall survival of about 12-15 years, the disease is heterogeneous. The 5 and 10 year overall survival (OS) of low, intermediate and high risk FLIPI is 91%, 78% and 53% and 71%, 51% and 36% using standard rituximab-based treatment. 5-year progression-free survival (PFS) is 80%, 70% and 48% respectively. Methods: Based upon this we conducted an investigator-initiated single-centre Phase II trial of intensified therapy with CHOP-R followed by (90)Y ibritumomab tiuxetan consolidation and 24 months of rituximab maintenance as treatment for patients with intermediate and high-risk newly diagnosed symptomatic follicular lymphoma. 33 patients were enrolled. Results: The addition of (90)Y ibritumomab tiuxetan was well tolerated but resulted in asymptomatic grade 3 or 4 thrombocytopenia and neutropenia in11-36% and 10-24% of patients between weeks 2-8 post (90) Y. After 9 years of follow-up (median follow-up 61 months) the 0S for intermediate and high risk FLIPI was 95% and 78%. The 5 year PFS was 79% and 64% for intermediate and high risk FLIPI, respectively. Responses at three months post consolidation were as follows: 3/33 (9%) achieved CR, 25/33(76%), achieved CRU, 1/33(3%) had PR, and 1/33(3%) had PD. Three patients did not receive (90)Y ibritumomab tiuxetan due to disease progression 2/33(6%), or death 1/33(3%). Of 19 patients who had a molecular marker for their lymphoma, 18 (95%) achieved molecular remissions in peripheral blood with CHOP-R therapy. Nine (47%) of these patients have been recently assessed for MRD and remain in molecular remission. The therapy resulted in decreased levels of IgG, IgM and IgA below the lower normal level in 33%, 40% and 23% of patients respectively post therapy. These levels did not recover in most of these patients. B cells were depleted to undetectable levels during therapy including rituximab maintenance. In 18 evaluable patients only 11 recovered normal B cell counts post maintenance rituximab. There was no correlation between normal B-cell recovery and Ig levels. Many patients with low or no B cell counts had normal IgG levels, whereas some patients who regained normal B cell counts were still unable to reach normal Ig levels. No patient developed human anti-mouse antibody. Immunity to measles, mumps, or rubella was retained post therapy. Patients did not have significant infections or opportunistic infections (although 2 developed Grade 1 shingles post (90)Y ibritumomab tiuxetan) and none required IVIG. Conclusions: We conclude that this intensified regimen is highly active in cyto-reducing lymphoma in high and intermediate risk FLIPI follicular lymphoma patients. The toxicity is tolerable although a significant percentage of patients will end up with persistent asymptomatic reductions in B cells and serum Ig. Only randomized trials will determine whether this regimen enhances outcome over standard of care in this higher risk follicular lymphoma population. References: 1.Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices. Nooka AK, Nabhan C, Zhou X, Taylor MD, Byrtek M, Miller TP, Friedberg JW, Zelenetz AD, Link BK, Cerhan JR, Dillon H, Sinha R, Shenoy PJ, Levy D, Dawson K, Hirata JH, Flowers CR. Ann Oncol. 2013 Feb;24(2):441-8. doi: 10.1093/annonc/mds429. Epub 2012 Oct 5 2.Validation, revision and extension of the Follicular Lymphoma International Prognostic Index (FLIPI) in a population-based setting. van de Schans SA, Steyerberg EW, Nijziel MR, Creemers GJ, Janssen-Heijnen ML, van Spronsen DJ. Ann Oncol. 2009 Oct;20(10):1697-702. doi: 10.1093/annonc/mdp053. Epub 2009 Jun 23. PMID: 19549712 Disclosures Buckstein: Novartis: Honoraria; Celgene: Honoraria, Research Funding.