ALBERT

Description: Background Despite the advent of rituximab (R)-based chemoimmunotherapy, outcome for patients with high-risk diffuse large B-cell lymphoma (DLBCL) continues to be suboptimal, and the risk of central nervous system (CNS) progression is high. In a previous Nordic phase II study with dose-dense chemoimmunotherapy followed by systemic CNS prophylaxis, the CNS progression rate was lower than expected (4.5%), but all events occurred within 6 months after initiation of therapy (Holte et al., Ann Oncol 2013). Hence, in the present study, systemic CNS prophylaxis was moved to the beginning of therapy and CNS targeted therapy was further intensified by adding intrathecally administered liposomal AraC. Methods Inclusion criteria are age 18-65 years, primary DLBCL or grade 3B follicular lymphoma without clinical or radiological signs of CNS disease and cytology negative cerebrospinal fluid (CSF), age adjusted IPI 2-3, WHO performance score ≤3, and/or site specific risk factors for CNS recurrence. Treatment consists of two courses of high dose (HD)-Mtx in combination with R-CHOP14, four courses of R-CHOEP14 and a course of HD-AraC with R. In addition, liposomal AraC is administered intrathecally in courses 1, 3 and 5. All courses are administered with support of pegfilgastrim. Indications for radiotherapy are bulky masses at diagnosis and localized PET positive residual disease not eligible for biopsy. Primary endpoints are failure-free survival at 3 years, and CNS progression rate at 18 months. A secondary aim is to elucidate if CSF cytology negative/flow cytometry (FC) positive cases carry an increased risk of CNS progression with the present regimen. Results Of the accrued 84 patients by July 22, 2013, 70 had a complete set of baseline data. Median age was 55 years (range 20-64). The majority presented with DLBCL (96%), advanced-stage disease (94%), elevated LDH (94%), B-symptoms (67%), and 49% with 〉1 extranodal site. Seven CSF-samples were FC positive. Data on toxicity, response and relapse rates were registered for 45 patients. One toxic death due to pneumonia was reported. Grade 4 hematological toxicity and infections were observed in 78% and 11% of the patients, grade 3-4 mucositis and gastrointestinal toxicity in 27% and 42%, and grade 3 arachnoiditis in 2.2% of the patients. CR, CRu, PR and PD rates at the end of chemoimmunotherapy were 69.0%, 14.3%, 14.3% and 2.4 %, respectively. After a median follow up time of 19 months, four patients have relapsed, two of whom with fatal CNS manifestations. Conclusions Preliminary results indicate highly satisfactory response rates and reasonable toxicity despite intensive therapy. HD-Mtx in combination with R-CHOP in the beginning of therapy and further intensification of treatment with CNS targeted liposomal AraC seem feasible and safe. ClinicalTrials.gov Identifier: NCT01325194 Disclosures: Leppa: Amgen: Research Funding; Mundipharma: Honoraria, Research Funding. Holte:Mundipharma: Honoraria, Research Funding; Amgen: Research Funding.

Description: Background: The Nordic Lymphoma Group has shown that adding cytarabine (AraC) and rituximab (R) to high dose CHOP and autologous stem cell transplantation increases response rate, event free survival (EFS), progression free survival (PFS) and overall survival (OS) of patients (pts) with MCL 〈 65 years (Geisler et al, Blood 2008). About 50% of pts with MCL are older than 65 years. Most of them are not candidates for high dose chemotherapy or transplantations and no satisfactory standard treatment is known for them. In this prospective pilot trial for elderly pts we explored the feasibility and efficacy of a prolonged standard dose induction treatment (10 cycles) with potentially synergistic combinations followed by R maintenance. Methods: Eligible were pts with histologically confirmed MCL (WHO criteria), CD5+, CD19/20+, cyclinD1+, age 〉 65 years, with adequate organ functions and performance status 〈 4. Induction: standard dose R-CHOP (cycles 1, 3, 5), R-AraC (R 375mg/m2 x 1, AraC 1g/m2 4 doses with 12 hrs intervals, cycles 2, 4), R-AraC with fludarabine (F) (2 doses of F 25 mg/m2, cycles 6 – 8), CHOP (cycles 9–10). Maintenance for pts with CR/PR: R 375 mg/m2 bimonthly x 12. Diagnostic workup included physical examination, CT scan, histological lymph node biopsy, bone marrow aspiration and biopsy, and immunohistology or flow cytometry of the diagnostic material. Endoscopies were performed for symptomatic patients. Responses were evaluated according to revised criteria (Cheson et al JCO 2007) after 5th, 8th, 10th cycles and after that every 6 months. Results: Thirty four pts were recruited. Age median 74 years (67–79 years). Performance status 0 n=12, 1 n=16, 2 n=3, 3 n=3. Stage IIA n=1, IVA n=20, IVB n=13. International prognostic index IPI 2 n=10, 3 n=13, 4 n=9, 5 n=2. Response to induction: CR 23, CRu 6, PR 3, PD 1, not evaluable 1. The response of 7 pts improved with cycles 6 to 8 (R-AraC with F). At diagnosis 32 pts had bone marrow involvement. At best response 24/25 pts with bone marrow involvement studied and CR (n=17), CRu (n=6) or PR (CTscan positive, n=1) were negative in flow cytometry (sensitivity 10−3–10−4). One patient with PR had residual MCL in flow cytometry. Median follow-up time of living patients is 26 months, range 6–43 months. There have been 8 events: progression or relapse 4, secondary AML 1, sudden cardiac death in CR 1, and 2 responding patients withdrew their concents. At 30 months EFS is 72%, PFS 77%, time to progression 85%, and OS 80%. Three pts have discontinued induction after 6,7 or 8 cycles due to toxicity but remain in CR. Infections grade 3 occurred in 8 pts and grade 4 in 1 patient. Eight pts have had transient neutropenia 〈 0.5 x 109/l during maintenance treatment. Conclusions: Elderly patients with MCL and with good performance status could be treated relatively intensively with moderate toxicity when supported with G-CSF. In historical comparison to CHOP, R, AraC and F increase response rate and prolong PFS, TTP and OS. Flow cytometry is a powerful tool to study bone marrow involvement at diagnosis and minimal residual disease. A longer follow-up is needed to evaluate the maintenance treatment but several patients have developed transient grade 4 neutropenia during maintenance treatment after this induction schedule.

Description: Abstract 2805 CHOP – based chemotherapy for aggressive lymphomas in patients with age-adjusted International Prognostic Index (IPI) score of 2–3 resulted in a historical 3-year progression free survival of approximately 30% in a previous Nordic phase III study. The aim of the present study is to determine whether an intensified regimen with chemoimmunotherapy and CNS prophylaxis improves outcome. Methods: From October 2004 to June 2008 patients were included in a phase II study. Inclusion criteria: 1) Age 18–65 years. 2) Newly diagnosed de novo diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade III. 3) No clinical sign of CNS disease and negative CSF cytology/flow cytometry by lumbar puncture. 4) No HIV infection. 5) WHO performance score 0–3. 6) Adequate organ functions. Schedule: Six courses of R-CHOEP14. Pegfilgrastim 6 mg sc. day four of each cycle. One course of high dose cytarabine 12 g/m2 (6 g/m2 for patients 60–65 years). One course of high dose methtrexate 3 g/m2 (1 g/m2 for patients 60–65 years). Biopsy and/or 18FDG PET/CT imaging of residual masses after fulfilled therapy was recommended, but not mandatory. Radiotherapy was given to residual masses of uncertain significance. Results. Demographic data:.156 eligible patients were included (97 males). Median age: 54 years (range 20–64). Histology: DLBCL: 145, FL grade 3: 12 (three patients no data). Age adjusted IPI score: 2: 117; 3: 39. Stage III-IV: 150 patients. LDH elevated: 151 patients. Performance status 2–3: 51 patients. B-symptoms were registered in 97 patients, more than one extranodal site in 42 and bulky lesions (≥ 10 cm) in 68. Median observation time for patients alive at last follow up was 36 months. Toxicity: Three toxic deaths are registered, one large bowel perforation, one fulminant hepatic necrosis and one septic shock. Hematological toxicity grade 4 was seen in 78% of the patients, infection grade 4 in 8%. Radiotherapy was given to 16% of the patients. Response: Response rates at end of therapy: CR/CRu: 69%, PR: 22%, SD: 1%, PD: 4.5%. Seventeen patients (7%) were not treated according to protocol, either due to lack of response (6 patients) or due to toxicity (eleven patients). The majority of the PR patients were considered to have residual masses and not viable tumour tissue. Survival: Three year overall survival was 80% (95% CI +/− 6.5%) and three year treatment failure free time 67% (95% CI +/−8.0%). CNS events: Seven patients had a CNS relapse, all but one were isolated (4 intracerebral, 3 meningeal). All CNS relapses occurred within 6 months after inclusion. Conclusions: The results are promising with a low three year treatment failure rate, a low toxic death rate and fewer CNS events than expected. The CNS events might be further reduced by earlier CNS prophylaxis. The study was supported by an unrestricted grant from Amgen Disclosures: Holte: Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. LeppÃ: Roche: Honoraria. Bjorkholm:Roche: Research Funding. Jyrkkiö:Roche: Honoraria. Kolstad:Roche: Honoraria; Amgen: Honoraria. Fosså:Roche: Honoraria. φstenstad:Roche: Honoraria; Amgen: Honoraria. Eriksson:Amgen: Research Funding.

Description: CHOP – based chemotherapy for aggressive lymphomas in patients with age-adjusted International Prognostic Index (IPI) score of 2–3 resulted in a historical 3-year progression free survival of approximately 30% in a previous Nordic phase III study. The aim of the present study is to determine whether an intensified regimen with chemoimmunotherapy and CNS prophylaxis improves outcome. Methods. From October 2004-June 2008 patients in Norway, Finland, Sweden and Denmark were included in a phase II study. Inclusion criteria: Age 18–64 years, newly diagnosed de novo DLBCL or FL grade III, no clinical sign of CNS disease and negative CSF cytology/flow cytometry by lumbar puncture, HIV negative, WHO performance status grade 0–3, adequate organ functions. Schedule: Six courses of rituximab and CHOP with the addition of etoposide 100 mg/m2 day 1–3 by i.v. route given every 14 day. Pegfilgrastim 6 mg sc. day 4 of each cycle. One course of cytarabine 12 g/m2 (6 g/m2 for patients 60–64 years). One course of methotrexate 3 g/m2 (1.5 g/m2 for patients 60–64 years). Biopsy and/or 18FDG PET/CT exam. of residual masses after fulfilled therapy was recommended, but not mandatory. Radiotherapy was given to residual masses of uncertain significance. Results. Demographic data: 160 patients were included (99 males). Median age: 54 years (range 20–64). Histology: DLBCL: 148, FL grade 3: 12. Age adjusted IPI score: 2: 120; 3: 40. Stage 3–4: 154 patients. LDH elevated: 154 patients. Performance status 2–3: 53 patients. B-symptoms were registered in 40% of the patients, more than one extranodal site in 23%, and bulky lesions (≥ 10 cm) in 43%. Data on toxicity and response rates were registered for 127 patients by Aug. 1st 2008 after the end of therapy and will be available for all patients by Dec 1st. Toxicity: Two toxic deaths were registered, one after large bowel perforation and one after an acute toxic necrosis of the liver. Hematological toxicity grade 4 was seen in 78% of the patients, infection grade 4 in 8%. Seven patients (5.5%) had major protocol deviations due to toxicity. Response: Two of the patients were non-responders at evaluation after 3 courses and were taken off therapy. Radiotherapy was given to 25 patients (20%). Response rates at end of therapy: CR: 54 (43%), CRu: 38 (30%), PR: 27 (21%), SD: 1 (1%), PD: 7 (5%). The majority (23/27) of the PR patients were considered to have residual masses and not viable tumor tissue and were observed without further treatment. Conclusions: Preliminary data indicate a low rate of toxic deaths despite intensive therapy. Remission rates are highly satisfactory for this subgroup of patients. Data are too premature for survival analysis at this time point.

Description: Introduction: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of early central nervous system (CNS) progression is high. Here we present the final results from a Nordic phase II study, where dose-dense chemoimmunotherapy including early systemic CNS prophylaxis with high dose methotrexate (HD-Mtx), further intensified by intrathecally (IT) administered liposomal cytosine arabinoside (AraC), was given. Patients and methods: Inclusion criteria were age 18-65 years, de novo DLBCL or grade 3B follicular lymphoma without clinical, radiological or cytological signs of CNS involvement, age adjusted IPI 2-3, WHO performance score 0-3, and/or anatomical sites related to increased risk for CNS recurrence (e.g. testis, facial sinuses, orbita). Treatment consisted of two courses of HD-Mtx in combination with R-CHOP14, followed by four courses of R-CHOEP14 and one course of R-HD-AraC. Liposomal AraC was administered IT at courses 1, 3 and 5 (omitted during a period of production halt). Primary end points were failure free survival (FFS; disease progression, discontinuation of protocolled therapy due to toxicity, death from any cause) and CNS progression rate at 18 months. Among the secondary endpoints were the identification of biological risk factors for high risk disease and prognostic role of cerebrospinal fluid (CSF) cytology-/flow cytometry (FC)+for CNS recurrence. Results: Of the accrued 143 patients, 140 met the inclusion criteria and were evaluable for baseline characteristics and primary endpoints. Of these, 132 had a complete set of treatment data. The male/female ratio was 1.7 and the median age 56 years (range 20-64). The majority of the patients had DLBCL (96%), advanced clinical stage (93%), elevated LDH (91%), more than one extranodal site (73%), and B-symptoms (64%). A bulky lesion (〉10 cm) was present in 37% of the patients and 11 CSF samples (8%) were FC+. Most patients (n=127, 96%) received a full treatment schedule. Liposomal AraC was given to 81 (61%) and radiotherapy to 39 (30%) patients. Grade 4 infections were observed in 12% of the patients. The frequency of grade 3-4 mucositis as well as gastrointestinal toxicity was 20%, and of grade 3 arachnoiditis 2,5%. Three toxic deaths were observed. In addition, three patients developed AML/MDS and one PML. At the end of treatment, CR/CRu, PR and PD rates were 79%, 17% and 3%, respectively. Of the 120 patients who underwent PET-CT, 92 (77%) achieved a metabolic CR (Deauville score (DS) 1-3). Three patients had primary refractory disease. At a median follow-up of 30 months, additional 14 patients had relapsed, three of them in the CNS (only one had a pre-therapeutic FC+ CSF), and 15 had died. FFS, PFS, OS and CNS progression rates at 30 months were 80%, 83%, 90%, and 2.4%, respectively. PET positivity (DS 4-5) at the end of treatment (p=0.019) and BCL2 expression (p=0.049) were associated with increased risk of progression, whereas other factors, such as molecular subtype (GC versus non-GC), Ki-67 score (≥70%), aaIPI group (2 versus 3), number of extranodal sites, FC-based CSF positivity, and treatment with liposomal AraC did not seem to have significant impact on outcome. Conclusions: Safety profile and final outcome results of the Nordic CHIC trial indicate high response rates, favorable survival, low number of CNS recurrences and manageable toxicity as a result of this CNS targeted intensive therapy schedule. PET response at the end of therapy and selected biological factors identify patients at high risk of progression. Disclosures Leppa: Roche: Honoraria, Other: Travel expenses, Research Funding; Janssen: Research Funding; Bayer: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Other: Travel expenses; CTI Life Sciences: Honoraria; Merck: Other: Travel expenses. Joergensen:Amgen: Research Funding; Mundipharma: Research Funding. Mannisto:SOBI: Honoraria; Pfizer: Honoraria; Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses. Jerkeman:Gilead: Research Funding; Celgene: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding; Janssen: Research Funding. Holte:Amgen: Research Funding; Mundipharma: Research Funding.

Description: Abstract 4110 Background: The ACT trial (ACT-1 and −2) tests the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP (A-CHOP-14) followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT/ASCT) in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). To date, the trial has accrued a total of 131 patients (ACT-1 n=72; ACT-2 n=59). Here, we present the first planned interim safety analysis of the ACT-1 trial based on the first 51 randomized patients. Aims: The aim of the present analysis is to report on the feasibility of a dose-dense chemo-immunotherapy schedule combining ALZ and bi-weekly CHOP followed by HDT/ASCT in ‘de novo' PTCL patients. Results: Results contain two data subsets corresponding to ALZ dose levels prior and subsequent to a dose-reduction amendment tapering ALZ dose from 360 mg (30 mg on days 1 and 2 of each CHOP course) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively. Of the 51 randomized patients, 43 had a complete set of evaluable data and represent the background for the present set of results. Of these, 5 received the higher ALZ dose, 17 the lower and 21 belonged to the antibody-void control arm. Treatment arms were well balanced with regard to histological subtypes, IPI sub-groups, and single prognostic factors. Neither of the two treatment cohorts, and for the experimental one irrespective of ALZ dose level, showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 3–4 leucopenia and anemia were more frequent in ALZ-treated patients (71% vs 29% and 47% vs 14%, respectively), whereas no difference was seen in terms of thrombocytopenia (17% vs 18%). Non-hematological toxicity unrelated to infectious complications was similar in the two groups. At the higher ALZ dose level, two cases of systemic fungal infection were reported, of which one (verified as being aspergillosis) with fatal outcome in a patient with pre-existing type II diabetes and steroid-requiring chronic obstructive pulmonary disease. These two events prompted the ALZ dose-reduction amendment, which led to a significant drop in the number of serious adverse events (SAEs) for ALZ-treated patients (SAE/patient pre-amendment: 2.6, post-amendment: 0.76) to a level comparable with the control arm (SAE/patient pre-amendment: 0.67, post-amendment: 0.44). With regard to the types of infection (≥grade 2), there was a similar frequency in reported fungal infections between the two treatment cohorts, bacterial infections were more often reported in the standard treatment arm (55% vs 46%), while the opposite was observed for viral infections (29% vs. 35%). Among the latter, there were 8 cases of cytomegalovirus reactivation among ALZ-treated patients, of which only two were clinically symptomatic and regressed upon specific treatment. Conclusion: In conclusion, the early-on impression of a SAE decrease subsequent to the ALZ dose-reduction amendment (applied on both ACT-1 and ACT-2) has been further confirmed by a larger cohort of patients treated at the lower ALZ dose level. The number of adverse events in the two study arms is now fairly comparable and adds further useful information to the previous reports on feasibility of stem cell harvest (Blood 2010;116: 2395) and hematopoietic recovery (Ann Oncol 2011;22(s4): 476) in ‘de novo' PTCL patients treated with a dose-dense ALZ-CHOP regimen followed by HDT/ASCT. Disclosures: Walewski: 4SC AG: Consultancy. Jantunen:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 57 Background The ACT trial (ACT-1, younger patients aged 18–60 yrs and ACT-2, elderly patients aged 〉60 yrs) is the first international randomized phase III trial in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). It tests, in both younger and elderly patients, the efficacy of the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP followed, only in younger patients (ACT-1), by high-dose therapy with autologous stem cell rescue. A dose reduction amendment tapering the cumulative ALZ dose from 360 mg (30 mg on days 1 and 2 of CHOP courses 1–6) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively, was introduced early on due to two cases of systemic fungal infection (Blood 2011,118;4110). To date, the trial has accrued a total of 186 patients (ACT-1 n=98; ACT-2 n=88). Aim Here, we present the results from the first interim efficacy and safety analysis of the ACT-1 trial based on the first 68 randomized patients. Results Of the 68 patients, 63 had a complete set of treatment data. The median follow-up was 15 months (range 0.5–42 months). Thirty-two patients belonged to the experimental arm (exp) and 31 to the standard arm (std). Of the 32 patients treated according to exp, 4 received the higher dose of ALZ and 28 the lower. Treatment arms were well balanced with regard to main prognostic features such as age (std: median 53 yrs, range 21–60 yrs; exp: median 50 yrs, range 22–64 yrs; p=0.705), IPI subgroups (std: low 10%, low-intermediate 51%, intermediate-high 29%, high 10%; exp: low 12%, low-intermediate 44%, intermediate-high 19%, high 25%; p=0.392), advanced clinical stage (std: stage III-IV 94%; exp: 97%; p=0.613), performance status ECOG〉1 (std: 23%; exp: 28%; p=0.613), elevated LDH (std: 68%; exp: 69%; p=0.932), presence of B-symptoms (std: 68%; exp: 75%; p=0.524), bulky disease (std: 13%; exp: 13%; p=1.0) and bone marrow involvement (std: 39%; exp: 31%; p=0.535). Histological subtypes were also similarly distributed among both treatment arms (std: PTCL-NOS 55%, AILT 23%, other 22%; exp: PTCL-NOS 56%, AILT 28%, other 16%). No cases of anaplastic large cell PTCL (regardless of ALK-protein status) were included. Neither of the treatment cohorts showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 4 leucopenia was more frequent in ALZ-treated patients (std: 24%, exp: 69%; p=0,001), whereas grade 3–4 anemia and grade 3–4 thrombocytopenia were not significantly different between treatment arms (anemia, std: 19%, exp: 31%; p=0,278; thrombocytopenia, std: 20%, exp: 12%, p=0,682). Non-hematological toxicity unrelated to infectious complications was mild and had a similar frequency in both arms. The number of serious adverse events (SAEs) per patient was 0.86 for patients treated at post-amendment ALZ dose levels, representing a significant reduction compared to the pre-amendment value (3.25), and 0.46 for patients treated in the control arm (p=0.002). The frequency of bacterial and fungal infections (grade ≥3) was similar in both treatment arms. ALZ treated patients had more viral events (9/32; 28% vs. 3/31; 10%), mainly (6 out of 9) consisting of asymptomatic cytomegalovirus reactivations. The overall (non-arm specific) 1-year event-free survival (primary end-point), progression-free survival and overall survival were 55% (95% CI: 42%-67%), 54% (95% CI: 42%-67%) and 78% (95% CI: 67%-88%), respectively. Conclusion The safety profile of the current standard and experimental treatment schedules, as well as the interim outcome results, support a continuation of the trial. A final analysis will be performed in Q2 2015. Disclosures: Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria.

Description: Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) with typically indolent clinical course. Although NLPHL is associated with favorable prognosis, late relapses, and a tendency to undergo transformation to aggressive lymphoma is seen in a substantial proportion of cases. Population-based long-term data on outcomes is limited. Aims We aimed to assess outcomes of the patients diagnosed with NLPHL in Finland. Methods We retrieved NLPHL patients diagnosed between 1995-2016 from the Finnish Cancer Registry (FCR) with complete follow-up to end of 2018. The Registry has an excellent coverage and provides accurate population-based nationwide data for all histologically verified cancers in Finland. Gender and events such as histologically verified progression and transformation were obtained from the FCR. Date of death or emigration was verified from the Population Register and underlying cause of death (COD) from Statistics Finland. COD was categorized into three groups: lymphoma, solid cancer, or other cause. Patients were categorized into diagnostic calendar periods (1995-2002, 2003-2010, 2011-2016), gender, according to relapse, transformation, and patient status (alive, dead, emigrated) by end of 2018. Standard descriptive statistical analyses were performed. Progression free survival (PFS) and all-cause overall survival (OS) was estimated via Kaplan-Meier method. Analysis of risk factors for OS and transformation was performed using the Cox proportional hazard model. Risk factors included diagnostic calendar period, age at diagnosis as a continuous variable (year), gender, relapse, and transformation. Multivariate analysis was performed including only factors with a p value 〈 0.05 from the univariate model. Two-tailed p-values 〈 0.05 were considered statistically significant. All statistical analyses were performed using R, version 4.0.2. Results We retrieved 414 patients with newly diagnosed NLPHL. Majority of the patients were males (n=320; 77%). Median age was 47 years (range 5 - 87), females being significantly older than males at diagnosis (59 vs 44 years; p 〈 0.001). We did not observe any statistically significant differences in age at diagnosis, gender distribution, progression, or transformation rates between the calendar periods. Five- and 10-year OS for the entire patient cohort were 89% and 84%, and 5- and 10-year PFS 77% and 64%, respectively (Fig. 1, 2). Eighty-six (21%) patients had at least one histologically verified progression (range 1 - 4). During the 11.1 years (range 0.7 - 23.9) follow-up, 81 (20%) patients died. The underlying COD was any lymphoma in 34 (42%), solid cancer in 14 (17%) and other cause in 33 (41%) patients. Gender, age at diagnosis, and transformation were included in the multivariate model with respect to OS. Age at diagnosis (HR 1.07; 95% CI 1.05 - 1.09), and transformation (HR 2.6; 95% CI 1.5 - 4.7), but not gender, remained independent. We found histologically verified transformation to large B cell lymphoma in 25 (7.4%) patients with ≥ 5-year follow-up from NLHPL diagnosis. Transformation was the first event in 15 (60%) patients, and 10 (40%) patients had one or more NLPHL progressions prior to transformation. The median age at the time of transformation was 57 years (range 20 - 87) and 17 (68%) of patients were males. The transformation free proportion over 5 years of follow-up was 96% and 93% over 10 years (Fig. 3). In multivariate analysis, gender, and age at diagnosis were not significantly associated with the risk of transformation. The 5-year OS after transformation was 50% which was significantly lower compared to the nontransformed patients with 5-year OS of 90%. Fourteen (56%) of the transformed patients died during follow-up, 13 from lymphoma and 1 from other cause. Conclusion In this large nationwide population-based study, females were 15 years older than males at the time of diagnosis. Twenty-five patients (7.4%) developed transformation to large B cell lymphoma. Age and transformation were independent risk factors for poor survival, whereas progression of NLPHL and gender were not associated with adverse outcome. We did not observe any survival difference between diagnostic calendar periods. Lymphoma was the main cause of death. Figure Disclosures Malila: Cancer Society of Finland: Current Employment. Jyrkkio:Hospital District of Southwest Finland: Current Employment.