Jørgensen, Judit

Abstract Introduction While outcomes in patients with R/R FL have improved with T-cell–redirecting treatments (e.g. CAR T-cell therapy, bispecific antibodies), there remains an unmet need for safe, efficacious, and more convenient chemotherapy-free treatment options (Caridà et al, Eur J Haematol. 2025). GOLCA is a potential, first-in-class, oral CELMoD agent designed for the treatment of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA drives the closed, active conformation of cereblon to induce rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing (agnostic of cell of origin) and immunomodulatory activity. In the two-part, multicenter, first-in-human Phase 1/2 study (CC-99282-NHL-001; NCT03930953), GOLCA was well tolerated and effective in patients with R/R FL (Cordoba et al, ICML 2025, #441). Here, we provide longer follow-up in patients with R/R FL from Part B of the study. Methods Patients with R/R FL with ≥ 2 prior lines of therapy (≥ 1 in Part B if prior anti-CD20 therapy) were included in the study. Patients received GOLCA monotherapy orally, once daily at different dosing schedules in Part A. In Part B, GOLCA was dosed at 0.2 or 0.4 mg (14 days on/14 days off) ± R. Total GOLCA treatment duration was up to 2 years or until progressive disease (PD)/unacceptable toxicity. Primary objectives included safety and recommended Phase 2 dose determination. Results As of April 3, 2025, a total of 72 patients with R/R FL were enrolled: 12 in Part A (GOLCA monotherapy) and 60 in Part B Cohort D (22 received GOLCA 0.2 mg + R; 38 received GOLCA 0.4 mg + R). Patients were heavily pre-treated. Median number of prior treatments was 4.5 (range, 2–6) in Part A and 3 (range, 1–12) in Part B Cohort D. Approximately one-third of the treated patients were exposed to prior T-cell–redirecting therapy, approximately one-third had prior lenalidomide (len) exposure, and approximately one-third were refractory to the last regimen received. At the time of data cutoff, in Part A, 4 patients completed 2 years of GOLCA, remaining in remission at last follow-up; 8 discontinued due to PD. In Part B Cohort D, 41% of patients treated with 0.2 mg and 63% with 0.4 mg were ongoing. PD was the most common reason for discontinuation. In the safety evaluable population (n = 60; GOLCA 0.2 or 0.4 mg + R), neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 treatment-emergent adverse event (TEAE) and occurred in 65% of patients, followed by anemia (13%) and febrile neutropenia (8%). Serious AEs related to GOLCA occurred in 22% of patients, most commonly infections (17%) and febrile neutropenia (7%); pulmonary embolism occurred in 1 patient with 0.2 mg. The most common causes of GOLCA interruption in the overall safety population were infections (32%) and neutropenia (18%). Dose reductions were mostly due to neutropenia (10%) and febrile neutropenia (5%). No discontinuations or deaths occurred from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade, with the most common being gastrointestinal disorders (7%). In the efficacy evaluable patients (n = 56; GOLCA 0.2 or 0.4 mg + R) at a median follow-up of 10.8 months, the overall response rate (ORR) was 89% (complete response rate [CRR], 61%). With 0.2 mg, ORR was 81% (CRR, 43%) and with 0.4 mg, ORR was 94% (CRR, 71%). In the 0.4-mg group, responses were consistent in high-risk subsets, including patients with prior len (ORR, 100%; CRR, 73%) and/or T-cell–redirecting therapy (ORR, 91%; CRR, 64%). With GOLCA 0.4 mg, 10 patients had response lasting > 12 months, including 5 with prior T-cell–redirecting therapy and 6 with prior len. Conclusions With additional follow-up, GOLCA + R continued to show promising efficacy with durable responses and no new safety signals. A higher ORR/CRR and similar tolerability were observed with GOLCA 0.4 mg + R vs GOLCA 0.2 mg + R, including in patients with prior len-based and/or T-cell–redirecting treatment. These data support continued development of GOLCA 0.4 mg + R as a fixed-duration, chemotherapy-free, outpatient option in the ongoing Phase 3 GOLSEEK-4 study in 2L+ FL (NCT06911502).

ABSTRACTThe development of new first‐line treatments for patients with follicular lymphoma (FL) is becoming increasingly challenging due to already excellent survival outcomes. The present study investigated the outcomes of patients with FL who underwent contemporary first‐line therapies but would not have been eligible for inclusion in recent trials and explored how commonly used in/exclusion criteria impacted their survival outcomes. This study included adult patients diagnosed with FL in the period 2000–2018 registered in the Danish Lymphoma Registry. Through searches on ClinicalTrials.gov, four recent 1st line phase 3 randomized controlled trials with R‐Bendamustine, R‐CVP, and/or R‐CHOP as control or experimental arms were included. Inclusion and exclusion criteria for each trial were retrieved and categorized. Patients were then divided into trial‐eligible and ineligible groups according to blood test results correlated to organ function and ECOG performance score (PS). Survival outcomes were significantly worse among trial‐ineligible patients, with adjusted differences between trial‐eligible and ineligible patients of 12%–20% in five‐year overall survival (OS) overall. Inclusion criteria based on PS and renal function were the main drivers of OS differences. More inclusive trials will lead to faster recruitment and secure focus on developing medicines for the group of patients with the worst outcomes.

Abstract Background: Generalizability of results from clinical trials with narrow in-/exclusion criteria are a concern as significant deviations in efficacy or toxicity may occur when treatments are used in populations of elderly and more comorbid patients. The cost-effectiveness of novel therapies may also be less favorable if real-world treatment effects are inferior to clinical trial results. In diffuse large B-cell lymphoma (DLBCL), a recent US study showed that baseline organ function-based eligibility criteria had substantial impact on survival with ineligible patients being at higher risk of dying from progressive lymphoma (1). Aims: The present study explored the impact of commonly used in-/exclusion criteria in key completed and ongoing first line DLBCL trials on survival in a Danish population-based study of patients with de novo DLBCL. Patients and methods: DLBCL patients enrolled in the Danish Lymphoma Registry (LYFO) and treated with R-CHOP in the period 2008-19 were screened for completeness of data to match trial eligibility criteria. The key organ/hematology eligibility criteria of completed or ongoing all-comers DLBCL studies (REMoDL-B, Goya, Polarix and Hovon84) were collected (bilirubin, ALAT, creatinine, eGFR, leucocytes, neutrophils, thrombocytes and ECOG). First, high-level trial matching on disease risk group (Ann Arbor, bulky disease, international prognostic index (IPI)) and age-groups were performed so that patients assessed for trial eligibility had a relevant risk profile. Subsequently, patients were divided into eligible or ineligible based on selected in/exclusion criteria. For each trial, overall survival (OS) from treatment start were compared for eligible and ineligible patients using inverse probability of treatment weighted Kaplan-Meier and log-rank tests. Crude OS and OS adjusted for residual imbalances in IPI and age were estimated. When possible, the OS curves from standard arms of the original trials were superimposed on OS plots. For each trial, the Shapley value of each criterion was calculated, using the HRs as well as the 5y restricted loss of lifetimes (RLOLs). The Shapley value measures the average influence of each eligibility criterion on the estimated IPI- and age-adjusted HR/5y RLOL. Results: A total of 3,150 R-CHOP treated DLBCL patients without discordant low-grade lymphoma were identified in the surveyed period. A total of 1,666 patients (52.89% of surveyed population) were available for the REMoDL-B trial, 1,431 (45.43%) for Goya, 1,125 (35.71%) for Polarix, and 1,432 (45.46%) for Hovon84. The variations of numbers for each trial evaluation were explained by trial inclusion criteria and missing data in LYFO. Crude OS estimates for patients with and without all necessary information were similar (data not shown). OS curves for eligible and ineligible patients are shown in Figure 1 and, when possible, with superimposed trial results (Goya, REMoDL-B, Hovon84). Survival differences between trial eligible and ineligible patients were robust to further adjustment of imbalances in age and IPI. Associated crude and adjusted 2 and 5-year OS rates for trial eligible and ineligible are shown in Table 1. The largest numerical difference in 2-year crude OS between eligible and ineligible was observed in the REMoDL-B trial (ineligible had 26% lower 2-year OS rate). The largest numerical difference in 2-year OS adjusted for IPI and age between eligible and ineligible was observed for the Polarix trial (ineligible had 17% lower 2-year OS rate). The strongest drivers of OS differences between trial eligible and ineligible patients in terms of the tested eligibility criteria were thrombocyte count (HR-contribution calculated from Shapley values -0.11; -0.14) and ECOG (HR-contribution -0.09; -0.21). Liver function parameters (bilirubin and ALAT) had low impact on OS (HR-contribution 0.00; -0.05 and 0.00; 0.07). Conclusions: The present population-based study confirms that trial ineligible patients have worse survival even after adjustments in imbalances in age and disease risk category. Thus, trial eligibility criteria have substantial impact on generalizability of results to a wider unselected population. Interestingly, the trial eligible patients identified in the present study had very similar outcomes to R-CHOP treated patients in the original trials supporting the possible use of RWD as synthetic control arms. Figure 1 Figure 1. Disclosures Maurer: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Nanostring: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jørgensen: Novartis: Consultancy; Gilead: Consultancy; Roche: Consultancy; Celgene: Consultancy. Larsen: BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Odense University Hospital, Denmark: Current Employment; Gilead: Consultancy. Clausen: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expences ASH 2019; Gilead: Consultancy, Other: Travel expences 15th ICML ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Poulsen: Abbvie: Consultancy; Janssen: Consultancy. El-Galaly: Abbvie: Other: Speakers fee; ROCHE Ltd: Ended employment in the past 24 months.

Abstract Disease progression after frontline therapy for Diffuse large B‐cell lymphoma (DLBCL) is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (SEAL) consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time‐dependent concordance indices (c‐statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post‐progression OS (both p < 0.001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c = 0.64, MER c = 0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post‐progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CAR‐T therapy as well as trial designs. The model is available in smartphone‐based point of care applications.

Background: Disease progression (PD) after frontline IC therapy for DLBCL is a clinically significant event and only 20-40% of patients achieve durable remissions with salvage chemotherapy. Patients who experience early PD or have disease refractory to IC have especially poor outcomes. Chimeric antigen receptor T-cell therapy has emerged as a novel effective therapy for selected cases of relapsed or refractory (r/r) DLBCL, although its availability is limited by cost and logistic challenges. Simple, clinically applicable prognostic tools would be useful for selecting patients for consideration for novel therapies vs those who are more likely to be successfully managed by conventional therapies, but few have been developed for r/r DLBCL. Methods: Model building was performed in patients with PD after IC from 13 frontline, multicenter, randomized DLBCL clinical trials from the SEAL Consortium. All patients received rituximab and an anthracycline-based combination IC and were followed systematically; however therapy received, clinical, and laboratory data at progression were not available. OS was defined as time from first progression until death from any cause. Associations between variables and OS were evaluated using Cox models; splines were used to model functional forms. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish LYFO cohorts. Model performance was assessed using time-dependent concordance indices (c-stat), Brier scores, and calibration with metrics evaluated at two years from progression. Results: Model Development (SEAL): 1125 of 5112 patients had PD after IC. Median time to PD (TTP) was 11.8 months (IQR 6.6-23.5); median age at PD was 68 years (IQR 60-73). At a median follow-up of 21 months from PD (IQR 7-43), 732 patients (65%) had died and 24 month overall survival after PD (OS24) was 35% (95% CI: 32-38). TTP was strongly associated with post PD OS (spline p-value&lt;0.0001) with OS24 ranging from 18% in patients with TTP &lt;6 months compared to 69% in patients with TTP &gt; 36 months (Figure A). Additionally, age at PD (spline p-value&lt;0.0001) was associated with post PD OS. A model consisting of age at PD including patients 40-80 years and TTP ranging 0-60 months was created (n=1011, Figure B) due to sparse data outside these intervals. C-stat was 0.67, and the model was well calibrated (predicted OS24 = 34% vs. actual OS24 = 34%). External Validation (MER): The model was validated in 290 patients with DLBCL who initiated 2nd line therapy after PD to IC. Median age at PD was younger than the SEAL cohort at 62 years (IQR 57-70). Patients with biopsy proven indolent histology at relapse were excluded. Median TTP was 8.2 months (IQR 5.1-17.0). At a median follow-up of 87 months from PD, 201 patients (69%) had died. OS24 was 47% (95% CI: 41-53). The model showed similar concordance (c-stat=0.65), but underestimated OS24 (predicted =33% vs. 47% actual, Figure C). External Validation (LYFO): The model was validated in 599 patients with DLBCL and PD after frontline IC. Median age at PD was 67 years (IQR 60-73). Median TTP was 10.1 months (IQR 6.0-19.4). At a median follow-up of 82 months from PD, 435 patients (73%) had died. OS24 was 38% (95% CI: 34-42). The model showed similar concordance (c-stat=0.67) when applied to the LYFO cohort, but again underestimated OS24 (predicted =32% vs. 38% actual, Figure D). Case vignettes: A 74 year old patient who progressed 9 months after diagnosis would have a predicted OS24 of 20%. A 58 year old patient who progressed 32 months after diagnosis would have a predicted OS24 of 65% Conclusions: TTP to following IC is strongly associated with post-progression survival in DLBCL. We developed a model from the largest frontline clinical trial dataset in DLBCL and validated a simple to apply clinical prognostic tool in the r/r setting. The model allows better understanding of expected outcomes in r/r DLBCL and can aid design and interpretation of trial results in this setting. The model underestimated the actual survival probability when applied to non-trial validation cohorts. Recalibration of the model for transplant eligible patients and development of smartphone based point-of-care application of the model is ongoing. Figure Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees. Schmitz:Riemser: Consultancy, Honoraria; Celgene: Equity Ownership; Gilead: Honoraria; Novartis: Honoraria. Farooq:Kite Pharma: Research Funding; Celgene: Honoraria. Flowers:Optimum Rx: Consultancy; Burroughs Wellcome Fund: Research Funding; BeiGene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bayer: Consultancy; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; National Cancer Institute: Research Funding; Denovo Biopharma: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Millenium/Takeda: Research Funding; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding. Frederiksen:Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding. Cunningham:Eli Lilly: Research Funding; 4SC: Research Funding; Bayer: Research Funding; MedImmune: Research Funding; Celgene: Research Funding; AstraZeneca: Research Funding; Merrimack: Research Funding; Sanofi: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Merck: Research Funding; Clovis: Research Funding. Jørgensen:Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Poeschel:Amgen: Other: Travel, accommodations, expenses; Abbvie: Other: Travel, accomodations, expenses; Hexal: Speakers Bureau; Roche: Other: Travel, accomodations, expenses. Nowakowski:F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Seymour:Takeda: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Acerta: Consultancy; Janssen: Consultancy, Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau. Merli:Takeda: Honoraria, Other: Travel Expenses; Gilead: Honoraria; Mundipharma: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Janssen: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Tilly:roche: Membership on an entity's Board of Directors or advisory committees; servier: Honoraria; merck: Honoraria; Gilead: Honoraria; Janssen: Honoraria; BMS: Honoraria; Karyopharm: Consultancy; Astra-Zeneca: Consultancy; Celgene: Consultancy, Research Funding; Roche: Consultancy. Salles:Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, 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, Other: Educational events; Epizyme: Consultancy, Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events. El-Galaly:Roche: Employment, Other: Travel support; Takeda: Other: Travel support.

SummaryNon‐endemic Burkitt lymphoma (BL) is a rare germinal centre B‐cell‐derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic‐based and population‐based lymphoma registries from six countries were used to identify 264 real‐world patients. The median age was 47 years and the majority had advanced‐stage disease and elevated LDH. Treatment protocols were R‐CODOX‐M/IVAC (47%), R‐hyper‐CVAD (16%), DA‐EPOCH‐R (11%), R‐BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two‐year overall survival and event‐free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two‐year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post‐remission event‐free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: −0·7 to 2) months. In conclusion, real‐world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow‐up strategies with increased focus on survivorship and less focus on routine disease surveillance.

Introduction: Non-endemic Burkitt lymphoma (BL) is a rare and highly aggressive B-cell malignancy, of whom a substantial number are adolescents and young adults (AYAs). In this particular group of patients, the balance between efficacy and long-term toxicities is of major concern, due to the long expected remaining lifetime. In this study, we investigated the outcomes for AYA patients treated with intensive immunochemotherapy. Patients and methods: Patients were identified through queries to clinic based and population-based lymphoma registries from six countries (Australia, Canada, Denmark, Norway, Sweden, and USA). All diagnoses were confirmed by local investigators; patients with classical BL histology plus detectable MYC translocation, were included. Patients between 18 and 39 years of age at diagnosis treated with intensive immunochemotherapy (DA-EPOCH-R or more intensively) were evaluated in pre-specified age groups. All treatment protocols included rituximab. Overall survival (OS) was defined as the time from diagnosis until death from any cause or censoring, while event-free survival (EFS) was defined as the time from diagnosis until unplanned re-treatment, progression/relapse, death, or censoring, whichever came first. Response evaluation was assessed using established response criteria based on CT and/or PET/CT imaging. Survival curves were computed using the Kaplan-Meier estimator. The cumulative incidence of relapse in patients reaching complete remission (CR) or CR unconfirmed (CRu) was computed by Aalen-Johansen estimator. The 5-year restricted loss of lifetime (RLOL) was defined as the area between the patient and general population survival curves until 5-years. The general population survival was retrieved from publicly available lifetables stratified on age, sex, calendar year, and country. Results: In total, 108 AYA BL patients were included. The median age was 30 years, ranging between 18 and 39 and 82% were male. The majority had advanced stage disease (Ann Arbor stage III-IV, 76%), extranodal involvement (87%), and elevated LDH (67%). Seven patients (6%) had CNS involvement at the time of diagnosis. The chemotherapy regimens used were CODOX-M/IVAC (51%), BFM/GMALL (34%), hyper-CVAD (7%), DA-EPOCH (5%), and others (3%). Among 74 patients for whom data on tumor lysis were available, 10 (14%) developed clinical tumor lysis upon start of chemotherapy, all presenting with advanced stage and extranodal disease. The response rate was 91% (89 in CR/CRu and 2% in partial remission). At a median follow-up of 53 months, 15 had an event and 10 died. The 2-year OS and EFS for the total population was 92% (87-97%, Figure 1) and 88% (82-94%), respectively. For 13 patients aged 18-21 2-year OS and EFS were both 100%, while 2-year OS and EFS for 43 patients aged 22-30 were 98% (93-100%) and 93% (85-100%), respectively. The 2-year OS and EFS for patients aged 31-39 were 86% (76-96%) and 80% (69-91%), respectively. For patients in CR/CRu and available date of response evaluation, the 2-year post-remission OS was 99% (97-100%) and the 2-year relapse risk was 2% (0-5%), with no relapses after 6 months. Compared to the general population, the RLOL was 0.8 months (-0.5-2.2 months). Nine patients did not respond to primary treatment (SD or PD), all which belonged to the age group 31-40 years (P<0.001 versus age group 18-30 years). The oldest age group had an inferior OS compared to younger patients (P=0.008), largely due to non-responders having poor subsequent survival with a 1-year OS of 33%. Conclusion: The outcomes of AYA BL patients following intensive immunochemotherapy are excellent with high remission rates and low risk of relapse in general. However, even among young patients age remained prognostic, with patients 31 years or older having inferior OS and lower response rate to first-line treatment. In patients achieving CR, survival was similar to that of the general population over the median follow-up of 4.5 years, illustrating the need to focus on survivorship issues in these individuals. Figure 1: Overall survival for BL patients following intensive immunochemotherapy for all patients and for age groups (18-21, 22-30, and 31-39 years). Figure 1 Disclosures Jørgensen: Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis: Honoraria, Other: Advisory board. Molin:Roche Holding AG: Honoraria; Merck & Co., Inc.: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria. Ekstroem Smedby:Takeda: Honoraria, Other: Grant funding, Research Funding; Celgene: Honoraria, Other: Grant funding, Research Funding; Janssen Cilag: Honoraria, Other: Grant funding, Research Funding. Song:Takeda: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria; Amgen: Honoraria. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Cheah:Roche, Janssen, MSD, Gilead, Loxo Oncology, Acerta, BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel expenses; Celgene, Roche, Abbvie: Research Funding. El-Galaly:Roche: Employment, Other: Travel support; Takeda: Other: Travel support.

Abstract Background: Non-endemic Burkitt lymphoma (BL) is a rare B-cell malignancy characterized by extreme tumor proliferation, frequent extranodal involvement, and the genetic hallmark of a MYC gene rearrangement. Despite an often dramatic initial presentation featuring tumor compression of vital organs and/or spontaneous tumor lysis syndrome, most patients who survive intensive immunochemotherapy induction are cured. Despite limited evidence of benefit, the current NCCN guidelines recommend that BL patients in CR are reviewed every 3 months for 2 years and every 6 months thereafter. Aims: To investigate outcomes, including relative survival and relapse risks conditional on event-free survival (EFS) milestones, in an international study of real-world BL patients treated with intensive immunochemotherapy. Patients and methods: This is a retrospective study of newly diagnosed BL patients identified from relevant population or hospital-based registers in Australia (Perth), Denmark (the Danish Lymphoma Registry), Sweden (the Swedish Lymphoma Registry) and Norway (Health Region South East). Patients who met the following criteria were included irrespective of HIV status: 1) age ≥18 years at diagnosis, 2) diagnosed during the period 2005-2017, 3) histology and immunohistochemistry consistent with BL, 4) MYC translocation detected by fluorescence in situ hybridization (FISH), and 5) intensive first line immunochemotherapy including rituximab (R-CHOEP or more intensive). Patient data were collected from registers and chart reviews. Overall survival (OS) was defined as time until death and EFS was defined as time to death, relapse/progression, or unplanned treatment, whichever came first. Prognostic features at baseline were evaluated using univariate Cox models with EFS as outcome. Standardized mortality ratios (SMRs), conditional relative survival estimates, and relapse risks were computed for the subset of patients achieving complete remission (CR or CRu), with follow-up measured from response evaluation and from different EFS milestones. Results: In total, 159 patients fulfilled the inclusion criteria of the study. The median age was 48 years (range 18-81) and the male:female ratio was 2.9. The baseline characteristics included stage III-IV (75%), elevated serum LDH (75%), extranodal involvement (83% - bone or bone marrow in 42% and CNS in 8%), B symptoms (60%), and ECOG performance score >1 (30%). The chemotherapy protocols used were CHOEP (2%), DA-EPOCH (13%), HYPER-CVAD (26%), CODOX-M/IVAC (28%), BFM or GMALL (31%), and others (1%). Clinical tumor lysis syndrome defined by severe electrolyte derangement, renal impairment, and/or cardiac arrhythmia, was noted in 16% of the patients, but no fatal episodes occurred. The overall response rate to first-line treatment was 88% (87% in CR/CRu) with 67% assessed by PET technology. The five-year EFS and OS estimates for the total population were 75% (95% CI 68-82%) and 82% (95% CI 76-88%), respectively, and the EFS and OS of patients <50 years of age were 81% (95% CI 71-90%) and 89% (95% CI 82-96%), respectively. In univariate analyses, age, advanced stage, and elevated LDH were associated with worse EFS. Among patients in CR/CRu (n=137), the 5-year EFS and OS from the time of response evaluation were 86% (95% CI 79-93%) and 91% (95% CI 86-96%), respectively. The 5-year cumulative incidence of relapse from the time of response assessment was 5% (95% CI 1-9%) in CR/CRu patients. The corresponding estimate was 3% (95% CI 0-6%) for patients alive after 6 months without events (EFS6), whereas no patients relapsed after 12 (EFS12, Figure 1). For CR/CRu patients, the 5-year relative survival after EFS6 and EFS12 was 97% (95% CI 93-102%) and 100% (95% CI 97-103%), respectively. In most subgroups, the SMRs gradually decreased with increased remission duration (Table 1). Conclusions: Outcomes of adult BL patients treated with intensive immunochemotherapy are excellent with no relapses occurring for patients reaching EFS12 and with a normalized relative survival after EFS6. For patients reaching EFS12, follow-up in late effects clinics, or discharging to primary care providers with a focus on survivorship issues rather than detection of recurrent lymphoma, should be considered. Updated analyses including patients from British Columbia (Canada) and the University of Iowa/Mayo Clinic SPORE MER register (USA) will be presented at the meeting. Disclosures Molin: Takeda Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Honoraria; Roche Holding AG: Honoraria; Merck & Co., Inc: Honoraria. Ekstroem Smedby:Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.