Long-term survey of survival time, histological transformation, and secondary malignancies in Japanese patients with advanced-stage follicular lymphoma in the rituximab era: Hokkaido Hematology Study Group

2014 ◽  
Vol 100 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Yasuo Hirayama ◽  
Kunihiko Ishitani ◽  
Shuithi Ota ◽  
Mitsutoshi Kurosawa ◽  
Takeshi Kondo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Survival Time ◽  
Japanese Patients ◽  
Study Group ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Histological Transformation ◽  
Hokkaido Hematology Study Group ◽  
Long Term Survey

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

Long-term survey of 443 cases of advanced-stage follicular lymphoma in Japan during the rituximab era.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e19504-e19504 ◽  
Author(s):  
Yasuo Hirayama ◽  
Kunihiko Ishitani ◽  
Shuithi Ohta ◽  
Mitsutoshi Kurosawa ◽  
Takeshi Kondo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Advanced Stage ◽  
Long Term Survey

Female Gonadal Toxicities after Treatment of Primary Hodgkin Lymphoma (HL). Analysis of the LENT-SOMA Questionnaire Registered in the Database of the German Hodgkin Study Group (GHSG).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4595-4595
Author(s):  
Karolin Behringer ◽  
Elena Gilman ◽  
Peter Borchmann ◽  
Eva Heuser ◽  
Beate Pfistner ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Hodgkin Lymphoma ◽  
Thyroid Dysfunction ◽  
Fourth Generation ◽  
Study Group ◽  
Advanced Stage ◽  
Gonadal Dysfunction ◽  
Regular Cycle ◽  
Remission Rates

Abstract Introduction: As a consequence of the impressive long-term remission rates in Hodgkin Lymphoma (HL), the reduction of treatment-related complications is becoming increasingly important. The most important treatment-related toxicities are secondary malignancies, infertility, pulmonary, cardiac, and thyroid dysfunction. Here, we report results of the prospectively planned LENT-SOMA questionnaire to determine female gonadal toxicities in women successfully treated for HL. Patients and methods: Between 1998 and 2002, the GHSG has conducted the fourth generation of clinical trials for the treatment of early, intermediate and advanced stage HL (HD 10–12) involving a total of approximately 4000 evaluable patients. The LENT-SOMA questionnaire was sent out to the participating centers 2, 5 and 10 years after a patient’s randomisation to evaluate cardiac, pulmonary, and gonadal dysfunction after HL treatment. To focus on female gonadal toxicities, questions referred to the menstrual cycle, infertility, and osteoporosis. Results: Overall, approximately 1.900 (50%) LENT-SOMA questionnaire after 2 years were identified. A total of 568 questionnaire were evaluable for the question of menstrual cycle after therapy. Amenorrhea was most frequent in women with advanced stage after treatment with 8 cycles of escalated BEACOPP compared to treatment consisting of 4 cycles of escalated BEACOPP plus 4 cycles of BEACOPP baseline (45% vs. 19%, p<0.0001). A regular cycle was most commonly reported in women treated with two or four cycles of ABVD (98.8% and 95.9%). The frequency of gonadal dysfunction will be evaluated according to treatment modality (chemotherapy, chemo- and radiotherapy) and it will be analysed with respect to age. Conclusion: Female gonadal toxicities after HL treatment include amenorrhea, infertility and osteoporosis. The first analysis of the LENT-SOMA questionnaire focussing on female gonadal dysfunction will be presented.

Long-Term Follow-Up of BEACOPPescalated Chemotherapy in Patients with Advanced-Stage Hodgkin Lymphoma on Behalf of the German Hodgkin Study Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 211-211
Author(s):  
Engert Andreas ◽  
Jeremy Franklin ◽  
Volker Diehl
Keyword(s):  
Hodgkin Lymphoma ◽  
Secondary Malignancy ◽  
Tumor Control ◽  
Study Group ◽  
Advanced Stage ◽  
Secondary Aml ◽  
German Hodgkin Study Group ◽  
Long Term Follow Up

Abstract The HD9 trial of the German Hodgkin Study Group (GHSG) compared two different doses (baseline and escalated) of the novel chemotherapy regimen BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage Hodgkin lymphoma (HL). The previous analysis with a median follow-up of 5 years showed improved tumor control (FFTF) and overall survival (OS) for BEACOPPescalated. Since BEACOPPescalated had been associated with more toxicity as compared with ABVD we report the results of long-term follow-up of 1196 patients enrolled and randomized in that study. The median follow-up was 112 months; a total of 370 centres contributed. Patients received one of three chemotherapy regimens: 8 cycles of COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) alternating with ABVD (doxorubicin, bleomycin, vinblastin, and dacarbazine), 8 cycles of standard-dose BEACOPP or 8 cycles of escalated-dose BEACOPP. At 10 years, FFTF rates were 64%, 70% and 82%, OS rates were 75%, 80%, and 86 for COPP-ABVD (arm A), BEACOPPbaseline (arm B), and BEACOPPescalated, respectively (p < 0,001). Importantly, BEACOPPescalated was also significantly better than BEACOPPbaseline in terms of FFTF (p < 0.0001) and OS (p = 0.0053). Death due to HL occurred in 11.5%, 8.1% and 2.8% in arms A, B, and C, respectively. 74 second malignancies were documented, including secondary acute myeloid leukaemias (1,7,14), Non-Hodgkin lymphoma (7,8,5), and solid tumors (7,16,9) in arms A, B, and C respectively. The corresponding overall secondary malignancy rates were 6.7%, 8.9% and 6.8%. Importantly, the risk of secondary AML (sAML), although increased in this study after BEACOPPescalated, amounts to 0.9% in our follow-up study with BEACOPPescalated (HD12) in 1502 advanced-stage HL patients randomized and four years median follow-up. Although the higher rate of secondary AML after BEACOPPescalated in HD9 most likely occurred by chance, interestingly, 70% of patients in this group had additional radiotherapy whereas only 39% were radiated in HD12. Taken together, the 10 years follow-up of BEACOPPescalated chemotherapy demonstrates a stabilized significant improvement in long-term FFTF and OS for advanced-stage HL. Although for formal prove the results of ongoing prospective randomized comparisons with 8 cycles of ABVD might be required, these results clearly challenge ABVD as standard of care for this patient population.

scholarly journals Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study

2021 ◽  
Vol 5 (17) ◽  
pp. 3354-3361
Author(s):  
Christian Buske ◽  
Wojciech Jurczak ◽  
Juan-Manuel Sancho ◽  
Edvard Zhavrid ◽  
Jin Seok Kim ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Induction Period ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Phase 3 ◽  
Double Blind ◽  
End Points ◽  
Term Efficacy

Abstract Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10–treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.

CHOP Improves Response Rates but Not Overall Survival in Follicular and Mantle Cell Lymphoma (MCL)- Results of a Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 611-611 ◽  
Author(s):  
Christina Nickenig ◽  
Martin H. Dreyling ◽  
Eva Schiegnitz ◽  
Michael Pfreundschuh ◽  
Lorenz H. Truemper ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Low Grade ◽  
Study Group ◽  
Advanced Stage ◽  
Conventional Chemotherapy ◽  
Mantle Cell ◽  
Lymphoma Study Group

Abstract In advanced stage follicular lymphoma conventional chemotherapy is non-curative and no major improvement in overall survival has been achieved by different regimens. Similarly, MCL, a lymphoma subtype with an especially poor clinical outcome, cannot be cured by conventional chemotherapy. In 1996, the German Low Grade Lymphoma Study Group (GLSG) started a randomized trial to evaluate the efficacy of two different anthracycline/anthrachinon containing regimens comparing CHOP (cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 2, adriamycine 50 mg/m2 day 1, prednisone 100 mg/m2 days 1–5) and MCP (mitoxantrone 8 mg/m2 days 1–2, chlorambucil 3x3 mg/m2 days 1–5; prednisone 25 mg/m2 days 1–5). 415 previously untreated patients with advanced stage indolent lymphoma were prospectively randomized to receive either 6–8 cycles of CHOP or MCP and are evaluable for induction therapy. 277 patients (67%) had a follicular lymphoma, 86 (21%) had a mantle cell lymphoma and 52 (13%) patients had another indolent histology. Responders up to 60 years were subsequently assigned to either myeloablative radiochemotherapy and autologous stem cell transplantation or to interferon-a maintenance (IFNa ), all other patients received IFNa. As stem cell mobilization was hampered in the MCP arm (only 44% sucessful mobilisations after MCP, 93% after CHOP; p=0.0003), from July 1998 all younger patients were asssigned to the CHOP arm. 86% complete and partial remissions (18% CR) were observed in the CHOP arm, whereas after MCP an overall response rate of 77% was obtained (14% CR, p=0.0094). In subgroup analysis similar improvement of remission rates were detected in follicular lymphoma (91% vs 82%, p=0.026) and mantle cell lymphomas (87% vs 73%, p=0.080). No differences, were observed, however, between both regimens for progression-free survival in both lymphoma subtypes. Overall survival was comparable for FL in both study arms (74% vs 69% at five years, p=0.29). In MCL, overall survival was slightly higher in the CHOP arm (5y OS: 57% vs. 31%; p=0.0578), but this difference was mostly due to unbalanced patient characteristics (IPI). In conclusion, CHOP appears superior to MCP in achieving a higher initial response rate but has no long term impact on response duration or overall survival.

Outcome of BEAM-Autologous and BEAM-Alemtuzumab Allogeneic Transplantation in Relapsed Advanced Stage Follicular Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2022-2022
Author(s):  
Victor Noriega ◽  
Anjum Bashir Khan ◽  
Stephen Devereux ◽  
Robert E. Marcus ◽  
Michelle Kenyon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
High Grade ◽  
Advanced Stage

Abstract Abstract 2022 Introduction: Follicular Lymphoma is the most common indolent lymphoma, characterized by an indolent course, multiple recurrence, responses to chemotherapy, risk of transformation into a high grade lymphoma and with a median overall survival of 10–12 years. Transplantation (autologous and allogeneic) has improved the overall outcome of this disease, however a continuous pattern of relapse is observed essentially in the autologous setting. Allogeneic transplant has shown encouraging results in terms of long term overall survival (OS) and disease free survival (DFS), with acceptable transplant related mortality (TRM) and with significantly lower relapse rate. Objective: To analyse retrospectively the outcome of relapsed follicular lymphoma patients who received BCNU (carmustine), cytarabine, etoposide, melphalan-alemtuzumab allogeneic HSCT (BEAM-C allo) or BEAM-autologous HSCT (BEAM-auto). Results: The study includes 74 consecutive patients with relapsed advanced stage follicular lymphoma who received BEAM-C allo (n=38) and BEAM-auto (n=36) between 1992 and 2010. Patients characteristics are summarized in Table 1. Median follow-up of surviving patients was 6.1 years. Patients undergoing allo transplants were younger than those who unbderwent and autologous procedure (50 vs 54 years, p=0.018). 1y and 5y TRM was higher in the allo transplant group (27% and 27% vs 6% and 6%; p=0,011). The Cumulative incidence of relapse (CIR) was lower in the allo at 1, 2 and 5 years (11%, 14% and 18% vs 28%, 49% and 60%, p=0,000). Significant differences were not observed in 1, 2 and 5 years OS between allo and auto transplant groups (74%, 74% and 69% vs 85%, 69% and 51%; p=0,217), but we found a strong trend in DFS difference between both groups at 1, 2 and 5 years (65%, 61% and 58% vs 69%, 43% and 33%; p=0.089) observing a plateau around 60% after 2 years in the allograft group. The rate of graft versus host disease (GvHD) was low with 14% acute GvHD (2.6% grade 3–4 GvHD) and 28% chronic GvHD (10% of extensive chronic GvHD). Analysis of the whole cohort (n=74) showed that patients in CR before transplant (n=28) had better 1, 2 and 5 years DFS following a allotransplant (69%, 69% and 69% vs 79%, 36% and 18%; p=0.012). These differences did not affect the 1, 2 and 5 years OS (76%, 76% and 76% vs 93%, 76% and 56%; p=0,214). TRM for the allo transplant group was 24% and 0% R in the auto (p=0,064) in patients when achieved CR before transplant. There were no difference in OS (p=0,785) and DFS (p=0,954) between allo or auto patients in partial response (PR) before transplant. A subgroup analysis of patients with high grade transformation before transplant did not show any differences in OS (p=0,823) or EFS (p=0,526).between allo and auto groups. Conclusions: Long term follow-up of Follicular Lymphoma patients has shown a continuous pattern of relapse when patients receive an autologous transplant, after 5 years. whereas patients undergoing allo transplant, despite a higher mortality, have a 5 year OS and DFS of 60% with a plateau been achieved in both curves after 2 years suggesting that these patients may be cured. Prospective randomised studies are still required to answer the the role of these two approaches in follicular Lymphoma. Disclosures: No relevant conflicts of interest to declare.

Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 614-614
Author(s):  
Paul M. Barr ◽  
Hongli Li ◽  
Richard Burack ◽  
Michael LeBlanc ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Free Survival ◽  
Grade 3

Abstract Background: Despite an abundance of effective therapeutic options, advanced stage follicular lymphoma (FL) remains incurable. Further, prospective trials consistently demonstrate that 20% of patients relapse within 2 years and ultimately have an inferior survival (Casulo 2015). Maintenace rituximab following chemoimmunotherapy induction is able to delay disease progression but has not demonstrated a benefit in overall survival (Salles 2011). Additionally, radioimmunotherapy (RIT) is one of the most effective single agent options in FL but is not commonly utilized as part of upfront treatment. As such, the role of both remains unclear. Based on results demonstrated with RIT consolidation in SWOG 0016 and the efficacy of rituximab maintenance, SWOG 0801 was designed as a phase 2 single arm trial, conducted to evaluate the utility of consolidative RIT and sequential maintenance rituximab following chemoimmunotherapy induction. Methods: Eligible patients (pts) with treatment naïve stage III/IV or bulky stage II FL received RCHOP for 6 cycles (without rituximab for the last 2 cycles) followed by iodine-131 tositumomab and subsequent rituximab administered every 3 months for up to 4 years. The primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints included 5-year overall survival (OS), overall response rate (ORR), and safety. Results: Of 87 pts registered to this study, 85 were deemed eligible following central pathologic review. One additional patient withdrew consent and received no treatment on protocol. Of the 84 evaluable patients, the median age was 52 years (range 29 - 80) ) and 18%, 40%, and 42%had low, intermediate and high risk FLIPI scores, respectively. Seventy-three pts completed RCHOP and I-131 tositumomab. Grade ≥3 AEs occurring ≥5% of pts included neutropenia (57%), leukopenia (40%), thrombocytopenia (20%), febrile neutropenia (17%), fatigue (10%), neuropathy (8%), anemia (7%) and hyperglycemia (5%). Reasons for discontinuation included refusal of tositumumab (6 pts), prolonged myelosuppression (2 pts), ascites (1pt), inability to provide tositumumab (1 pt), and an unrelated lower extremity wound (1 pt). Following induction and RIT, 59 complete responses and 23 partial responses were observed, for a ORR of 99% (95% CI: 93.5%, 99.9%) Sixty nine eligible patients registered to maintenance therapy with 42 completing the 4 year treatment plan. The only grade ≥3 AE that occurred in ≥5% of pts was leukopenia (5%). Twenty-seven pts discontinued maintenance therapy, including 11 in the first 2 years and 16 in the last 2 years, due to the following reasons: infection (8 pts), patient preference (8 pts), deaths (2 pts), treatment delay (2 pts), secondary solid tumors (2 pts), bowel perforation (1 pt), joint pain (1 pt), hepatic transaminase elevation (1 pt), insurance refusal (1 pt), and dose error (1 pt). Four additional secondary malignancies were reported following completion of therapy including solid tumors (3 pts) and AML (1 pt). To date, 9 deaths have occurred due to secondary malignancies (3 pts), unknown etiology (3 pts), cardiac arrest (2 pts) and non-alcoholic cirrhosis (1 pt). After median follow-up of 5.6 years (range 3-7 years), 17 events have occurred including 9 pts experiencing progressive FL resulting in a progression free survival of 90% (95% CI: 81.9%, 95.1%) at 3 years and 84%(95% CI: 74.5%, 90.6%) at 5 years (Figure). Three-year overall survival is 96% (95% CI: 89.3%, 98.8%) and 5-year overall survival is 94% (95% CI: 86.2%, 97.5%). Conclusions: SWOG 0801 demonstrates near universal responses following chemoimmunotherapy and RIT. This sequential therapeutic strategy appears to improve early outcomes as 94% of pts are without disease progression at 2 years, consistent with the best results ever demonstrated for FL in the National Clinical Trials Network. However, the majority of discontinuations occurred during maintenance suggesting that rituximab over a 4-year span is not feasible for many patients due to cumulative toxicity. Future studies investigating precision strategies in high-risk FL may consider an aggressive chemoimmunotherapy induction and RIT consolidation platform to overcome early FL progression given these promising outcomes. Support: NIH/NCI grants CA180888, CA180819, and in part by GlaxoSmithKline. Figure. Progression-Free Survival and Overall Survival Figure. Progression-Free Survival and Overall Survival Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Smith:Amgen: Other: Educational lecture to sales force; Juno: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Portola: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; TGTX: Consultancy. Gopal:Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy. Persky:Merck: Research Funding; Gilead: Speakers Bureau. Press:Roche / Genentech: Consultancy, Research Funding. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Other: Data Safety Monitoring Committee.

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