Abstract: Background: Most patients (pts) with diffuse large B-cell lymphoma (DLBCL) receiving first-line (1L) rituximab plus CHOP (R-CHOP) have similar mortality to the general population (gen popn) if they are progression-free at 24 months (PFS24; Maurer et al. Ann Oncol 2018). Characterization of quality of life (QoL) and clinical outcomes may enable more patient-relevant treatment decisions. Using GOYA trial data (NCT01287741) comparing obinutuzumab (G) + CHOP (G-CHOP) with R-CHOP, we present an exploratory analysis of 1L DLBCL pts with IPI 2-5 and assess overall survival (OS) and QoL relative to the gen popn. GOYA was not included in the previous PFS24 analysis by Maurer et al. Methods: We used data from both GOYA treatment arms to identify pts with IPI 2-5 DLBCL (n=1132 pts, intent-to-treat popn). Post-progression survival (PPS) in DLBCL is independent of prior treatment (Coiffier et al. Blood 2010) and as PFS was similar between treatment arms in GOYA, we assumed similar mortality after PFS24. Clinical outcomes were PFS24 (progression-free ≥24 months [m] from treatment start); early relapse (disease progression [PD] & lt;24m from treatment start); late relapse (PD after PFS24). Outcomes for study pts vs gen popn were evaluated using standardized mortality ratios (SMR; deaths in study pts relative to expected deaths in gen popn matched by age, sex, country, and calendar time-at-risk). Expected deaths were derived using the Human Mortality Database, which provides detailed mortality and population data by country and can be used to estimate the background mortality during the observation period. Post-relapse survival in pts with early vs late relapse was assessed using Kaplan-Meier (KM) estimates and Cox regression. QoL was assessed using EQ-5D-3L and UK-based tariffs (Dolan. Med Care 1997); association between QoL and clinical outcomes used a linear mixed-effects model. The proportion of pts with PFS24 reporting QoL problems at baseline and after 24m was compared with age- and country-matched values in the gen popn (Janssen et al. Springer 2014). Data cut-off was Jan 2018 (GOYA final data cut); overall median follow-up was 48m. Results: In the overall IPI 2-5 population, mean age at treatment initiation was 61 yrs. 711 pts reached PFS24, of whom 64 experienced a late relapse (Table 1). Early relapse was experienced by 261 pts, of whom 164 were & lt;6 months from end of treatment (EOT). OS following PFS24 was 98.6% at 2 years (including patients who later relapsed). 2-year PPS was 35.7% for pts with early relapse vs 74.8% for patients with late relapse (Figure 1.) Mortality following PFS24 was 72% of the matched gen popn (SMR 0.72; not significant: 95% CI 0.44-1.11). Mortality following relapse in pts who experienced early relapse was over 33 times higher than expected in the matched gen popn (SMR 33.57, 95% CI 27.69-40.33). However, risk of death following late relapse was reduced by 78% compared with risk following early relapse (HR 0.22 95 CI% 0.12-0.40), and mortality following late relapse was significantly higher than in the matched gen popn (SMR 6.7, 95% CI 3.05-12.67). Mean QoL utility score at baseline was 0.69 for all pts. After pts reached PFS24, estimated mean utility score was 0.86 (95% CI 0.84-0.87) and worsened by -0.07 (95% CI -0.14 to -0.01) at time of subsequent relapse. For early-relapsing pts, the worsening in utility was -0.15 (95% CI -0.20 to -0.10) compared with those still progression-free (Table 2). Among all PFS24 pts at baseline, problems were reported with mobility (28.1%), self-care (12.6%), usual activities (41.8%), pain/discomfort (62.7%), and anxiety/depression (48.8%); these rates were 2.2-4.7 times higher than the gen popn based on age- and country-standardized values. Compared with the gen popn, after pts reached PFS24, pain/discomfort was 10% lower, whereas anxiety/depression was 34% higher and other QoL items were approximately 20% higher. Conclusions: Most of the clinical course of 1L DLBCL occurred ≤2 years after start of treatment. In DLBCL pts with IPI 2-5 achieving PFS24, mortality was similar to the gen popn, and with the exception of mental health metrics, QoL scores were also similar to the gen popn. Late relapse (≥2 yrs) was associated with better post-relapse survival than early relapse ( & lt;2 yrs); however, this was inferior to the gen popn. Health state utilities improved whilst patients were relapse-free but the decline in QoL after early relapse was worse than after late relapse. Figure 1 Figure 1. Disclosures Launonen: F. Hoffmann-La Roche Ltd: Current Employment. Ho: F. Hoffmann-La Roche Ltd: Current Employment. Knapp: F. Hoffmann-La Roche Ltd: Current Employment. Canales Ruiz: Clinical Project Manager in Clinica Universidad de Navarra: Current Employment. Simonella: F. Hoffmann-La Roche Ltd: Current Employment. Thuresson: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company.

Abstract: Introduction: Progression of disease within 24 months of initial therapy (POD24) is associated with poor survival in patients with follicular lymphoma (FL). Existing prognostic models, such as FLIPI-1 and FLIPI-2, show poor sensitivity for POD24, and are derived from cohorts lacking bendamustine-treated patients. More accurate predictive models based on current standard therapies are needed to identify patients with high-risk disease. The Phase III GALLIUM trial (NCT01332968) compared the safety and efficacy of standard chemotherapy regimens plus rituximab (R) or obinutuzumab (G) in patients with previously untreated FL. Using GALLIUM data, we developed a novel risk stratification model to predict both PFS and POD24 in FL patients after first-line immunochemotherapy. Methods: Enrolled patients were aged ≥18 years with previously untreated FL (grades 1-3a), Stage III/IV disease (or Stage II with bulk), and ECOG PS ≤2, and required treatment by GELF criteria. Patients were randomized to receive either G- or R-based immunochemotherapy, followed by maintenance with the same antibody in responders. The chemotherapy arm (CHOP, CVP, or bendamustine) was selected by each study center. POD24 was defined as progressive disease or death due to disease within 24 months of randomization (noPOD24 = no progression or lymphoma-related death in that period). The most strongly prognostic variables, based on PFS hazard ratios, were estimated using penalized multivariate Cox regression methodology via an Elastic Net model. Selected variables were given equal weights, and a clinical score was formed by summating the number of risk factors for each patient. Low- and high-risk categories were determined using a cut-off that provided the best balance between true- and false-positives for PFS. PFS correlation and sensitivity to predict POD24 were assessed. The data used are from an updated GALLIUM efficacy analysis (data cut-off: April 2018; median follow-up: 57 months). Results: 1202 FL patients were enrolled. Based on data availability and biological plausibility (i.e. could reasonably be linked with high-risk disease), 25 potential clinical and treatment-related prognostic variables were entered into the Elastic Net model (Table). A model containing 11 factors was retained by the methodology and chosen as the best model (Table). Patients were categorized as 'low risk' if they scored between 0 and 3 (n=521/1000 patients with complete data) and as 'high risk' if they scored between 4 and 11 (n=479/1000 patients). At 2 years, the PFS rate was 84.5% in the whole FL population. Using our model, 2-year PFS for high-risk patients was 77% compared with 79.9% for FLIPI-1 and FLIPI-2. In low-risk patients, 2-year PFS was 92% compared with 87.9% for FLIPI-1 and 87.6% for FLIPI-2 (low-intermediate-risk patients). Our model increased the inter-group difference in 2-year PFS rate from 8% (FLIPI-1) and 7.7% (FLIPI-2) to 15%. At 3 years, the inter-group difference increased from 6.9% (FLIPI-1) and 9% (FLIPI-2) to 17% (Figure). Sensitivity for a high-risk score to predict POD24 was 73% using our model compared with 55% for FLIPI-1 and 52% for FLIPI-2 (based on 127 POD24 and 873 noPOD24 patients with complete data). Excluding patients who received CVP, which is now rarely used, resulted in an inter-group difference in PFS of 15% at 2 years and 16.8% at 3 years. A sensitivity analysis showed that inclusion of the 9 clinical factors only (i.e. removal of CVP and R treatment as variables) formed a more basic scoring system (low-risk patients, 1-3; high-risk patients, 4-9); the inter-group difference in PFS was 16.5% at 2 years and 17.6% at 3 years. However, sensitivity for POD24 decreased to 56%. Conclusion: Our clinical prognostic model was more accurate at discriminating patients likely to have poor PFS than either FLIPI-1 or FLIPI-2, and its prognostic value was sustained over time. Our model also identified the FL population at risk of POD24 with greater sensitivity. Variables such as age and bone marrow involvement were not retained by our model, and thus may not have a major impact in the current era of therapy. Factors such as sum of the products of lesion diameters were included, as this captures tumor burden more accurately than presence of bulk disease. Future studies will aim to improve the accuracy of the model by considering gene expression-based prognostic markers and DNA sequencing to form a combined clinico-genomic model. Disclosures Mir: F. Hoffmann-La Roche: Employment. Hiddemann:F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Marcus:F. Hoffman-La Roche: Other: Travel support and lecture fees; Roche: Consultancy, Other: Travel support and lecture fees ; Gilead: Consultancy. Seymour:Genentech Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bolen:Roche: Other: Ownership interests PLC*. Knapp:Roche: Employment. Launonen:Launonen: Other: Ownership interests none PLC; Travel, accommodation, expenses; Novartis: Consultancy, Equity Ownership, Other: Ownership interests none PLC; Travel. accommodation, expenses; Roche: Employment, Other: Travel, accommodation, expenses. Mattiello:Roche: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Oestergaard:Roche: Employment, Other: Ownership interests PLC. Wenger:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership, Other: Ownership interests PLC. Casulo:Gilead: Honoraria; Celgene: Research Funding.

Abstract: Introduction: The treatment regimens bendamustine and rituximab (BR), and rituximab, gemcitabine, and oxaliplatin (R-GemOx) have proven to be efficacious and have manageable safety profiles for transplant-ineligible patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL; NCCN guidelines 2020). However, there is a paucity of published data from randomized clinical trials (RCTs) to determine the comparative efficacy of R/R DLBCL treatments (Vander Velde et al. Hematol Oncol 2019) and limited evidence from real world studies (Ionescu-Ittu et al. J Comp Eff Res 2019). One of the most recent RCTs to evaluate BR as a treatment backbone in this setting is the Phase Ib/II GO29365 study (NCT02257567). In this study, polatuzumab vedotin combined with BR (Pola+BR) significantly improved progression-free survival (PFS) and overall survival (OS), compared with BR alone in pts with R/R DLBCL (Sehn et al. J Clin Oncol 2020). In order to compare survival of pts treated with BR or R-GemOx in the second line (2L) setting, we performed a retrospective analysis using real-world data (RWD) from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) cancer registry linked to Medicare enrollment data and insurance claims. Methods: Pts with cancer diagnoses from 2004 to 2016 were identified using the SEER Medicare database. Pts diagnosed with DLBCL not otherwise specified (ICD-O-3 histology code: 9680) who received 2L BR or R-GemOx alone, were included. Additional inclusion criteria were: pts aged & gt;65 years at diagnosis, with DLBCL as their first or only primary cancer diagnosis, and other standard SEER Medicare analysis criteria such as minimum Medicare enrollment of 12 months, to ensure sufficient data for analysis. Pts with evidence of prior hospice care were excluded. Accurate identification of transplant-ineligible pts is a limitation of using the database; transplant ineligibility was assumed for this population based on their age and associated risk factors. Survival was assessed by Kaplan-Meier and Cox regression analysis. The inverse probability-of-treatment weighting (IPTW) method was applied to balance baseline characteristics such as age at the start of 2L treatment, gender, stage of disease, race, Charlson Comorbidity Index (CCI), relapsed or refractory status, time from initial treatment to 2L treatment initiation, calendar year of 2L start, and health maintenance organization. Analyses of pts treated in the third line (3L) setting were also performed. Results: Of the 3,606 pts with DLBCL within the database, 439 pts (BR: n=308; R-GemOx: n=131) met all study criteria and were included in the analysis. Median follow-up was 12.42 months (interquartile range [IQR]: 4.78-28.41) for pts treated with BR, and 7.72 months (IQR: 3.02-21.14) for pts treated with R-GemOx. Pts treated with R-GemOx were more likely than pts treated with BR to be younger or male (Table). There was a similar proportion of pts who were primary refractory in each treatment group (BR: 20.8%; R-GemOx: 21.4%; p=0.99). The unadjusted median duration of 2L treatment was 11.4 weeks (IQR: 4.29-20.04) with BR and 8.14 weeks (IQR: 4.07-14.71) with R-GemOx. Median OS was 16.39 months (95% confidence interval [CI] : 13.01-19.48) with BR and 8.74 months (95% CI: 7.00-12.98) with R-GemOx (Figure A). After adjustment for covariates, median OS was 16.39 months (95% CI: 12.88-19.48) with BR and 9.26 months (95% CI: 7.10-14.36) with R-GemOx (Figure B); the hazard ratio (HR) for adjusted OS in 2L was 1.24 (95% CI: 0.97-1.58) for R-GemOx compared with BR. After propensity score adjustment, the HR for OS in 3L was 0.996 (95% CI: 0.70-1.42) for R-GemOx compared with BR. Conclusions: OS was not significantly different between pts with R/R DLBCL treated with BR or R-GemOx in this RWD analysis from the SEER Medicare database. This type of analysis is limited by the assumption that all important variables have been accounted for in the propensity scoring, and by the inclusion of only pts who were recorded in the database, which may impact how these results can be generalized. Nonetheless, in the absence of comparative data from RCTs, this RWD analysis demonstrates similar real-world effectiveness of the two regimens in R/R DLBCL. Disclosures Castro: F. Hoffmann-La Roche Ltd: Current Employment. Surinach:Seattle Genetics: Research Funding. Launonen:F Hoffman-La Roche Ltd: Current Employment; Novartis: Divested equity in a private or publicly-traded company in the past 24 months. Thuresson:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Felizzi:F. Hoffmann-La Roche Ltd: Current Employment.

Abstract: Introduction: Standard of care for previously untreated patients (pts) with diffuse large B-cell lymphoma (DLBCL) is rituximab (R) plus 6-8 cycles of CHOP (R-CHOP). While the RICOVER trial (Pfreundschuh et al. Lancet Oncol 2008) showed no benefit of 6 versus 8 cycles of R-CHOP administered at 2-weekly intervals, this has not been assessed with the standard 3-weekly regimen, and many centers continue to administer 8 cycles. GOYA (NCT01287741) was an open-label, randomized, Phase III study of the efficacy and safety of R-CHOP versus obinutuzumab (GA101; G) plus CHOP in previously untreated pts with DLBCL. The current exploratory analysis compared investigator (INV)-assessed progression-free survival (PFS) and overall survival (OS) in pts receiving 6 or 8 cycles of CHOP in combination with 8 cycles of R in GOYA. Methods: Eligible pts were aged ≥18 years with histologically documented, CD20-positive DLBCL and ≥1 bi-dimensionally measurable lesion, ECOG PS 0-2, IPI score ≥2, and adequate hematologic function. Low-risk pts with IPI score 1 not due to age alone or 0 with bulky disease (1 lesion ≥7.5cm) were also eligible. Pts who were randomized to R-CHOP received 8 cycles of R (375mg/m2) in combination with 6 (CHOP6) or 8 (CHOP8) cycles of CHOP. Centers elected upfront to administer either 6 or 8 CHOP cycles to all pts enrolled at that site. Efficacy was evaluated in all pts who were randomized to R-CHOP (intent-to-treat population; data cut-off: January 31, 2018). Safety was assessed in all pts who completed the 6th treatment cycle and received R in the 7th cycle (CHOP6 safety population: no additional CHOP cycles; CHOP8 safety population: at least 7 or 8 CHOP cycles received). Only AEs starting during or after the 7th cycle were considered. Statistical analyses included Kaplan-Meier estimates and Cox-regression, with and without propensity score adjustment to correct for baseline imbalances. Results: Results are reported for 712 pts who were randomized to R-CHOP (CHOP6, n=526; CHOP8, n=186; safety population: CHOP6, n=461; CHOP8, n=144). In the CHOP6 group, 55% were male and median age was 62 years (range 54-70). In CHOP8, 49% were male and median age was 60 years (range 47-67). Baseline characteristics were broadly comparable across treatment groups, except for geographic region (CHOP6 vs CHOP8: Asia, 32% vs 49%, respectively; Eastern Europe, 10% vs 24%; Western Europe, 36% vs 13%; North America, 18% vs 8%; other, 4% vs 5%). In CHOP6, 89% completed 6 cycles of R-CHOP, while in CHOP8, 76% completed 8 cycles. Three-year INV-assessed PFS rates were comparable between groups: 68.7% in CHOP6 versus 66.8% in CHOP8 (HR 0.92; 95% CI: 0.69, 1.23; Figure 1a). Three-year OS rates appeared higher in the CHOP6 group (83.2% vs 76.2% in CHOP8; HR 0.65; 95% CI: 0.46, 0.91; Figure 1b). PFS and OS comparisons were unchanged after propensity score adjustment for the prespecified baseline characteristics, including age, gender, disease stage, geographic region, IPI score, extranodal sites, body surface area, bulky disease, LDH, and COO (PFS: HR 0.96, 95% CI: 0.70, 1.32; OS: HR 0.66, 95% CI: 0.45, 0.97). Interim treatment response (by CT) did not influence these findings. Model-based subgroup analysis according to baseline pt characteristics did not identify any pt subgroups benefitting from 8 versus 6 cycles of CHOP (Figure 1c). Incidence of grade 3-5 adverse events (AEs) was lower in the CHOP6 group than in the CHOP8 group (17.8% vs 38.9%, respectively); cardiac AEs (all grade: 2.4% vs 6.3%; grade 3-5: 1.3% vs 3.5%) and infections (all grade: 10.6% vs 23.6%) were also less common. In support of these findings, similar results were achieved after repeating the same efficacy analysis in pts who received 6 or 8 cycles of CHOP in combination with 8 cycles of obinutuzumab. Conclusions: In this exploratory analysis of 712 previously untreated DLBCL pts in GOYA, in which the number of CHOP cycles was selected upfront by each site, no additional PFS benefit was observed with 8 cycles of R-CHOP compared with 6 cycles of R-CHOP plus 2 cycles of R, even after adjusting for baseline differences, including COO and IPI. Slow response, assessed by interim CT, did not influence these findings. Furthermore, incidence of grade 3-5 AEs (including cardiac) and any grade infections was markedly higher in pts receiving 8 cycles of CHOP versus 6 cycles. These results suggest that rituximab with 6 cycles of 3-weekly CHOP should be considered standard of care. Disclosures Sehn: Janssen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Culligan:JAZZ: Honoraria; Celgene: Other: Support to attend conferences; Takeda: Honoraria, Other: Support to attend conferences; Daiichi-Sankyo: Other: Support to attend conferences; Abbvie: Other: Support to attend conferences; Pfizer: Honoraria; Merck Sharp & Dohme (MSD): Honoraria. Ogura:Cellgene: Honoraria; Celltrion: Research Funding; Takeda: Honoraria; SymBio: Research Funding. Launonen:Roche: Employment, Other: Travel, accommodation, expenses; Novartis: Consultancy, Equity Ownership, Other: Ownership interests none PLC; Travel. accommodation, expenses; Launonen: Other: Ownership interests none PLC; Travel, accommodation, expenses. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Sellam:Roche: Employment. Trněný:Morphosys: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; F. Hoffman-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Gilead: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Sandoz: Honoraria; Abbvie: Honoraria, Research Funding. Vitolo:Gilead: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sandoz: Speakers Bureau. Martelli:Servier: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; F. Hoffman-La Roche: Membership on an entity's Board of Directors or advisory committees.

Abstract: Introduction: Predicting the risk of histologic transformation (HT) from indolent follicular lymphoma (FL) to a more aggressive form of lymphoma represents a major challenge in managing patients with FL. We assessed the incidence of HT in the GALLIUM study (NCT01332968) and determined risk factors for transformation and impact on clinical outcomes. Methods: In the Phase III GALLIUM study, patients with previously untreated FL were randomized to receive either the anti-CD20 antibody rituximab (R; 375mg/m² on Day (D) 1 of each cycle) or obinutuzumab (G; 1000mg on D1, 8, and 15 of Cycle 1 and D1 of subsequent cycles) in combination with chemotherapy (CHOP, CVP or bendamustine). Patients who achieved at least a partial response at the end of induction therapy proceeded to maintenance therapy with the same antibody, every 2 months for 2 years, or until progression of disease. Repeat biopsies at progression were not mandatory but carried out in case of clinical suspicion of HT. The rate of HT, as assessed by the local pathologist, in patients with a repeat biopsy at the time of disease progression/relapse was an exploratory endpoint. Results: 1202 patients were enrolled. After a median follow up of 57.3 months, 315 (26.2%) patients progressed (median time to relapse, 25.3 months); of these 315 patients, 46 (14.6%) had a biopsy at first progression due to a clinical suspicion of transformation. Forty patients, corresponding to 3.3% of all patients enrolled in GALLIUM and 12.7% of those that progressed, had biopsy-confirmed HT. Among 153 patients with disease progression within 24 months (POD24), 31/153 (20.3%) had HT. Fewer patients transformed in the G-chemo arm (16/40; 40%) compared with R-chemo (24/40; 60%). In total, 116 patients relapsed in the G-chemo arm versus 159 in the R-chemo arm. Compared with no HT, patients with HT were more likely to be male and have bone marrow involvement, stage 3A FL, high FL International Prognostic Index risk, low hemoglobin (Hb), elevated serum lactate dehydrogenase (LDH), elevated beta-2-microglobulin, and high total metabolic tumor volume (Table). A comparison of chemotherapy backbones showed a trend towards higher HT incidence with bendamustine (5.8% [26/686]) compared with CVP, 4.3% (5/117) and CHOP, 2.3% (9/399). A multivariate cause-specific cox model identified several risk factors for HT, including elevated LDH levels (hazard ratio [HR] , 4.27 [95% CI: 2.08─8.78]; p 〈 0.0001), anemia (Hb levels 〈 12 g/dL; HR, 2.01 [95% CI: 0.99─4.11]; p=0.0547) and male gender (HR, 2.36 [95% CI: 1.23─4.55] ; p=0.0102). Competing risks were non-progression-related death and relapse without HT. Although there appeared to be a trend towards a higher incidence of HT with bendamustine, the sample size was too small to allow for conclusions. Considering all patients with progressive disease, 16/40 patients with HT and 37/275 relapsed patients overall died within 2 years of relapse (56.0% vs 83.1% post-progression/relapse survival rate, respectively). Of the POD24 patients that died, 19/66 (28.8%) were patients with HT. Among patients with disease progression within 12 months (POD12), overall survival (OS) was unfavorable in patients both with and without transformation: 28/56 FL relapsed POD12 patients died within 2 years of relapse (survival rate, 48.3%; median post-progression survival, 1.88 years) and 13/23 POD12 patients with HT died within 2 years of relapse (survival rate, 41.0%, median post-progression survival, 0.94 years; Figure 1A). Among the 153 POD24 patients, those with HT (n=31) had worse outcomes (16/31 POD24 patients with HT died within 2 years of relapse with a survival rate of 46.8%), compared with 33/122 FL relapsed POD24 patients (survival rate, 72.2%; Figure 1B). Conclusions: In GALLIUM, a low rate of HT was observed over 5 years, with the majority occurring within the first 2 years. Patients with POD12 had poor OS regardless of whether transformation occurred or not. Risk factors for HT included elevated LDH, anemia, and male gender. Patients with HT, especially those with progression of disease within 24 months, had poor OS compared to patients who relapsed with persistent FL. Disclosures Casulo: Celgene: Research Funding; Gilead: Honoraria, Other: Travel, accommodation, expenses; Roche: Other: Travel, accommodation, expenses. Herold:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; GILEAD: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Hiddemann:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Bayer: Research Funding; Vector Therapeutics: Consultancy, Honoraria. Iyengar:Roche: Honoraria; Abbvie: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Marcus:Roche / Genentech: Honoraria, Speakers Bureau; Gilead: Consultancy. Seymour:AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy; Acerta: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding. Launonen:F. Hoffmann-La Roche Ltd: Employment. Knapp:F. Hoffmann-La Roche Ltd: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Mir:Roche: Other: Previous employment.