ALBERT

Description: Introduction Results of randomized studies showed benefit of maintenance therapy with monoclonal anti-CD20 antibody (rituximab) in terms of time to progression (PFS) and overall survival (OS) in follicular lymphoma (FL). General recommendation, based on large clinical trial, is to give 2 years of rituximab maintenance á 375mg/m2every 2 months (12 doses) in first line setting. On the other hand, there are various rituximab maintenance schedules; however, the clear comparison of clinical efficacy is missing. Our retrospective analysis compared two different schedule of rituximab maintenance in first-line treatment of FL used in university centers participating on CLG registry. Methods Data were recruited from 1702 FL patients registered in the prospectively maintained multicentric database (Czech Lymphoma Group; CLG). For the analysis, patients with stage II-IV of new diagnosed FL (grade 1-3a) responding (complete or partial remission) to 6-8 cycles first-line RCHOP (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone) followed with rituximab maintenance (RM) were included. Completed planned maintenance was inclusion criterion. Patients with previous watch and wait or additional first line therapy (radiotherapy, other chemotherapy, transplant therapy) were excluded. Results Totally, 168 evaluable FL patients with median age 57ys (range 28-82) including 70 (41.7%) men treated with RCHOP + RM were found in CLG database. 52/168 patients received totaly 8 doses of rituximab maintenance every 3 months for 2 years (RM8 arm), whereas 47/168 patients were treated with totaly 12 doses (RM12 arm) of rituximab maintenance every 2 months for 2 years. All patients in both subgroups completed planned RM therapy. There was no difference in distribution of age, gender, FLIPI, grade, B-symptoms, bone marrow involvement, performance status, LDH and beta2microglobuline level between both arms. Induction treatment in terms of administered cycles CHOP (6xCHOP in 41/52 and 35/45 pts., for RM8 and RM12 arm) and rituximab doses (8xR in 48/52 and 41/45 pts., for RM8 and RM12 arm) was similar between arms (ns). There were 4/52 (7.7%) and 5/47 (10.6%) relapses in subgroups RM8 and RM12, with no statistical significance. Median PFS was 3.8 (2.1-5.8) years vs. 3.9 (2.4-7.8) years in RM8 and RM12 arms (not significant), and median OS 3.91 (2.2-6.94) years vs. 3.1 (2.48-8.6) years also with no statistical significance. Conclusion Our results show, that rituximab maintenance given every 2 or every 3 months for two years in first line treatment brings similar benefit to the FL patients in terms of remission duration and overall survival. Despite the fact, that presented data are retrospective observation, this is the first report comparing two different rituximab maintenance regimens in FL. Further prospective study and longer follow up are needed to confirm our preliminary data. This work was supported by grant NT/12193-5 and MHCZ-DRO (FNBr 65269705) Disclosures: Mayer: Roche: Consultancy, Research Funding; Glaxo: Consultancy, Research Funding. Trneny:Roche: Honoraria, Research Funding.

Description: Background: Follicular lymphoma (FL) is an indolent lymphoma with chronically relapsing disease course. Treatment of relapses with 2nd line regimens such as salvage and autologous stem cell transplant (ASCT) is considered successful, i.e. the relapse itself does not shorten life expectancy. However, LymphoCare registry study (Casulo et al., JCO 2015) identified an early progression of the disease (POD24, i.e. progression within 24 months after R-CHOP commencement) to be a strong unfavorable event. Early progressors experienced only 50% 5-year OS compared to 90% in the control group) irrespective of the salvage treatment delivered. It is unclear whether post R-CHOP maintenance immunotherapy (MAINT) decreases POD24 incidence. Potential predictors identifying patients at risk of POD24 have not been analyzed yet. Aims: (1) To analyze the impact of MAINT on POD24 occurrence, (2) to find clinically applicable predictors of POD24 at the time of FL diagnosis. Methods: The Czech Lymphoma Study Group (CLSG) database was searched using the LymfoCare (LC) study methodology for previously untreated FL grade I-IIIa patients (pts), CS II-IV (Ann Arbor), no watch-and-wait before R-CHOP. Early progressors were defined as pts with progression or relapse within 24 months after FL diagnosis. OS was calculated both from diagnosis and from the Risk-defining event (rdOS) - it means from the date of early progression (POD group) or 24 months after diagnosis (non POD group). We have identified 821 FL pts, who met the inclusion criteria above and were diagnosed before DEC-2014. Median age of the CLSG group (58 years; range 26-82 years) was identical to the LC group (58 years; 22-88). Fifty-eight percent were females (46% in LC) and 50.5 % had high risk FLIPI (44% in LC). 80.8% of our pts had FL grade I-II and 19.2% had FL grade IIIa (62% and 38% in LC, respectively) Results: Treatment response was available in all but 15 pts (99.9%): CR/CRu, PR and SD/PD was achieved in 70.0%, 25.5% and 4.5%, respectively. After median follow up of 5.02 years 244 (29.7%) pts relapsed or progressed and 101 (12.3%) of the pts died. Five year OS and progression-free survival (PFS) was 90.1% (95% CI 0.88-0.92) and 63.7% (95% CI 0.60-0.68), respectively. In total, 99 POD24 (12.3%) were identified in the whole cohort of 821 patients. Five-year OS without POD24 (93.8%) was superior to 5-year OS in the POD24 group (64.3%, p

Description: Background Follicular lymphoma (FL) is a disease with very heterogeneous course ranging from the indolent forms to rapidly progressive cases with poor outcome. Optimal therapy in FL patients with high tumor burden is immunochemotherapy (R-CHOP is the most frequent regimen used), followed by maintenance treatment. Data from randomized prospective studies (PRIMA) showed poorer outcome in those with high risk disease in terms of lower CR rate, higher risk of relapse and lower efficacy of maintenance therapy. Data comparing up-front intensive approach in younger fit patients and R-CHOP are limited. Aim To analyze long term results of intensive treatment protocol (R-sequential chemotherapy) in comparison with age, FLIPI and maintenance delivery matched (R-CHOP) controls. Methods Here we analyzed data of 48 prospectively enrolled FL patients who were treated by sequential (R-SQ) chemotherapy with or without up-front autologous stem cell transplant (ASCT) as a part of stratified risk adapted treatment in one institution. For R-SQ regimen were indicated patients3mg/L and/or thymidine kinase〉15 IU/L) or HIGH-FLIPI patients (irrespective of additional risk factors). R-SQ protocol consists of alternating three cycles of etoposide-doxorubicine regimen (PACEBO), one methotrexate-ifosfamide regimen (IVAM), and one cycle of high dose cytarabine regimen (HAM). Remission was consolidated with 6th cycle of chemotherapy (PACEBO) in INT-FLIPI patients (n=22, 46%) or with ASCT with BEAM-200 conditioning (n=26, 54%) in HIGH-FLIPI patients. Maintenance immunotherapy was applied for historical reasons in 24 patients (50%). Controls were randomly selected from the Czech Lymphoma Study Group (CLSG) database from 626 cases with confirmed FL grade I to IIIa, treated with R-CHOP. Pair matching was performed on 1:3 basis, controls were matched by age, FLIPI and rituximab maintenance application. In the end, we analyzed intensive SQ-group (n=44) and standard control R-CHOP-group (n=144). Maintenance therapy was delivered to 24 patients (50%) in R-SQ group and to 72 patients (50%) in R-CHOP-group (P=1.00). Results Median age of SQ-group was 47.6 years compared to 48.7 years in R-CHOP (P=0.44), FLIPI index was equally distributed: INT-FLIPI (43% vs 43%), HIGH-FLIPI (57% vs 57%, P=1.00). Treatment response quality was higher in SQ-group than in R-CHOP-group: CR/CRu 93.8% vs 70%, PR 6.2% vs 23% and SD/PD 0% vs 8% respectively (P=0.01). During the follow-up, (median 3.5 and 6.1 years in R-CHOP and SQ-group respectively, P

Description: Introduction Localized stages of follicular lymphoma (I-II) have been traditionally treated with involved field radiotherapy (IF-RT), which seems to be able to cure a significant proportion of patients. On the other hand, nearly half of patients relapse within 10 years. The late distant relapses remain the problem. Rituximab (anti CD20 antibody) is low-toxic, efficient systemic therapy for follicular lymphoma (FL). In vitro models bring the evidence of significant synergism between rituximab and radiotherapy. Up to now, there are no clinical data about clinical benefit of rituximab addition to the IF-RT. This study compares IF-RT alone vs. IF-RT with rituximab in early-stages of FL. Methods Between 2005-2012, through the prospectively maintained multicentric database (Czech Lymphoma Group; CLG), we identified patients with stage I-II FL treated with IF-RT (dose ≥ 24Gy) or IF-RT (dose ≥ 24Gy) with rituximab or rituximab alone. Patients receiving IF-RT with chemotherapy were not included. Complete staging including CT (neck, thorax, abdomen and pelvis) and bone marrow biopsy was performed at diagnosis. We compared EFS and OS between these three treatment arms. Rituximab (4 doses á 375mg/m2) was administered prior start of radiotherapy in combined arm. The total doses of rituximab varied between 4-8 doses á 375mg/m2 in rituximab monotherapy subgroup as well as in combined arm. Response to treatment was evaluated with CT 6-12 weeks after last dose of therapy. Results For the study period, approximately 1700 pts. of FL were identified in CLG database; 101pts with stage I-II FL (grade 1-3A) were included in the analysis. 65 patient were treated with radiotherapy alone (RT), 14 pts. with rituximab alone (R) and 14 pts. received rituximab and radiotherapy (R+RT), 8 pts. were excluded because of incomplete data. Median follow up was 4.57 (2.25- 12.6) years since diagnosis. There were no differences of age, performance status, FLIPI, proportion of bulky or extranodal tumor. In subgroup treated with R+RT was higher proportion of FL grade 3A in comparison with R or RT alone arms (35% vs. 1.5% vs. 7.5%; p.007). Complete response rate was 92% in RT arm, 100% in arm with R+RT and 86% in group treated with R alone, difference did not reach statistical significance. Median of event free survival was 3.35years in RT group, not reached in R+RT arm and 5.1 years in patients treated with R alone. EFS differences are statistically significant (p.035), but with no impact on overall survival. Conclusions In spite of fact, that RT is considered to be a good initial treatment for localized FL, rituximab alone or better in combination with RT seems to give better results in terms of long-term global control of disease. Our preliminary results should be confirmed with other studies and longer follow up is needed to verify or not the impact of rituximab on survival in early stages of FL. The work is support by research grant NT/12193-5 and MHCZ-DRO FNBr65269705. Disclosures: Mayer: Roche: Consultancy, Research Funding; Glaxo: Consultancy, Research Funding. Trneny:Roche: Honoraria, Research Funding.

Description: Background: The outcome of DLBCL patients is improving, it however seems to be very poor for those who are refractory to the therapy. We have decided to analyze this group of patients. Methodology: As part of an observational clinical study NiHiL (GovTrial No NCT03199066) we identified the patients treated in the first line by R-CHOP like immunochemotherapy who met at least one criterium: 1. refractory (stable disease - SD or progression) on 1st line therapy (1st l- R), 2. refractory (SD or progression) on salvage (platinum based regimen) (Salv-R), 3. refractory to or relapse/progression within 12 months after ASCT (ASCT-R/R). There were 210 patients diagnosed in the period 2001-2017 who fulfilled the criteria. Progression-free survival (PSF) and overall survival (OS) were estimated from the time of determination of a refractory disease. Results: The cohort consisted of 163 patients primarily resistant to the first-line therapy, 31 patients were resistant to the salvage therapy and 16 patients progressed within 12 months after ASCT . At the time of the diagnosis, the median age was 65 years (22-91) (the same as at the refractory disease), 54% were males, 74% had advanced clinical stage (III+IV), 68% had IPI 〉3, 77% had above-normal LDH, and 45% had a tumor mass 〉10cm. The OS from the time of determination of refractory disease was 0.53 years, median PFS was 0.29 years. Patients under 65 years had median survival 0.8 years compared to 0.4 years in the group of patients above 65 years of age. The median PFS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.3, 0.26 and 0.35 years resp. and 5y survival 22%, 0% and 6% resp. The median OS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.55, 0.39 and 0.65 y resp. and 5y survival was 28%, 0% and 13% resp. Our results demonstrate that resistant DLBCL has an extremely poor prognosis, clearly new effective therapeutic strategies such as CAR-based therapies or others are required. This work was supported by a research program Progres Q28-9. Disclosures Belada: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Abstract 1641 Rituximab has proven efficacy and tolerability for treating B-cell malignancies. IV rituximab administration can take several hours, consuming considerable healthcare resources. A SC rituximab formulation has been developed which may shorten administration time, increase patient (pt) convenience, and potentially reduce IV administration-associated costs. Rituximab efficacy depends on CD20 binding, and Ctrough rituximab levels reflect rituximab exposure throughout the therapy cycle; therefore, achieving a non-inferior Ctrough level with SC dosing is expected to provide comparable efficacy to IV dosing. BP22333 (NCT00930514) is a two-stage phase Ib study assessing PK and tolerability of SC vs IV maintenance rituximab in pts with first-line or relapsed FL. Stage 1 dose-finding results (Salar et al, ASH 2010, abstract 2858; Salar et al, EHA 2012, abstract 0794) identified a fixed dose of 1400 mg for formal Ctrough non-inferiority testing in Stage 2. We report Stage 2 data. The Stage 2 objective was to demonstrate non-inferiority of simulated Ctrough of rituximab SC and IV, using a non-inferiority test with a lower boundary of 0.8 for the 90% confidence interval (CI). Secondary endpoints include SC vs IV rituximab safety and area under the serum concentration-time curve. Eligible pts (N = 157) were aged ≥18 years with an ECOG performance status of ≤ 2, and histologically confirmed CD20-positive grade 1, 2, or 3a FL requiring treatment. Eligible pts must have achieved a complete or partial response following IV rituximab-based induction therapy for FL and have received ≥1 cycle of IV rituximab maintenance within 16 weeks of completing induction. Pts (N = 154) were randomized 1:1 to receive SC rituximab (1400 mg) or IV rituximab (375 mg/m2) for their remaining maintenance cycles, stratified by 2-monthly (q2m) vs 3-monthly (q3m) regimen. Study arms were balanced for age, sex, body surface area, FL grade at diagnosis, induction therapy and number of maintenance doses prior to study entry. As of May 11, 2012, 13 SC pts had withdrawn (7 for progressive disease [PD], 4 for AEs, 1 at investigator's decision, 1 for ineligibility) and 17 IV pts had withdrawn (10 for PD, 4 for AEs, 3 for ineligibility). Median treatment duration on-study was 14.8 months (range, 0–19) in the SC arm and 13.8 months (range, 0–19) in the IV arm. The primary endpoint of the study was met. Geometric mean Ctrough,SC:Ctrough,IV ratios were 1.24 and 1.12, respectively, for q2m and q3m, and lower limits of the two-sided 90% CI (1.02 and 0.86, respectively) exceeded the protocol-specified non-inferiority limit (Ctrough,SC:Ctrough,IV ratio of 0.8). Therefore, 1400 mg SC rituximab was concluded to be non-inferior to 375 mg/m2 IV rituximab administration. AE incidence and intensity were generally balanced; 79% of pts in each arm experienced AEs. Serious AEs were observed in 12% and 14% of pts in the SC and IV arms, respectively; none occurred in 〉 1 pt in either arm. Grade 3/4 AEs occurred in 18% and 17% of pts in the SC and IV arms, respectively; the only grade 3/4 AEs occurring in 〉 1 pt in either arm were neutropenia (2 pts in each arm) and arthralgia (2 pts in the IV arm). Administration-related reactions (ARRs) were the most frequent AE and had a higher incidence in the SC arm (reported in 31% of SC vs 4% of IV pts). ARRs were mostly local reactions; the most common in the SC arm were: erythema (13%), injection site erythema (5%), and myalgia (5%). Further safety data will be presented. PK data for SC and IV rituximab administration demonstrate non-inferiority of 1400 mg rituximab SC administration to that of the approved IV rituximab maintenance regimen for both q2m and q3m schedules. The overall AE profiles were similar for SC and IV rituximab administration, with the exception of local ARRs, which had a higher incidence in the SC arm compared with the IV arm, reflecting the expected change in the ARR profile with SC administration. Induction and maintenance therapy using the 1400 mg SC rituximab dose is being assessed in the phase III BO22334 study. Disclosures: Salar: Roche: Consultancy. Off Label Use: Subcutaneous (SC) administration of rituximab as maintenance therapy in patients with follicular lymphoma (FL). Larouche:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brewster:Roche: Employment, Equity Ownership. Catalani:Roche: Employment, Equity Ownership. McIntyre:Roche: Employment. Sayyed:Roche: Employment. Haynes:Roche: Consultancy, Honoraria.

Description: Background: Early events within 24 months (POD24) of initial immunochemotherapy (IC) were repeatedly confirmed to be associated with poor survival in follicular lymphoma (FL). Rituximab maintenance (RM) given to responding patients after IC is effective strategy to reduce relapse incidence and improve survival (Salles, Lancet 2011; Hill, BJH 2019). There is little known about the POD24 incidence pattern in chemosensitive patients, and the impact of subsequent RM application for POD24 reduction has not been studied yet. Aim: To (1) analyze the role of POD24 events in patients with responding FL and (2) describe whether post-induction RM changes the pattern of POD24 incidence and possibly post-POD24 outcome of the patients. Methods: The study comprised patients prospectively enrolled in the Czech Lymphoma Study Group network (ClinicalTrials.gov: NCT03199066) in 2000-2015, with grade 1-3A FL and treated with frontline R-CHOP/R-CHOP-like or R-bendamustine or R-CVP IC. Cases with previous WaW were not enrolled. No frontline stem cell (auto/allo) transplant was allowed. Only patients who achieved complete (CR/CRu) or partial remission (PR) at the end of induction (EOI) and were thus potential candidates for RM were included. Early event was defined as progression, relapse or death within 24 months after the date of EOI response assessment. Overall (OS) and progression-free survival (PFS) were calculated from the date of diagnosis and date of EOI response (OS-EOI). Patients who experienced an event before the median time to RM initiation were excluded from POD24 survival analyses to avoid overestimation of the RM group results. Results: A total of 1089 patients were identified, of whom 729 (67%) received RM (maintenance group) and 360 (33%) were followed without RM (observation group; OBS). When comparing both groups, we found no differences in age (median age 59 yrs for both; P=0.54), sex distribution (males 39% vs. 41% in OBS vs. RM, respectively; P=0.37) and ECOG 0-1 (90% vs. 93% in OBS vs. RM; P=0.10). There was a slightly lower proportion of advanced FL (Ann Arbor III-IV) in OBS (80%) as compared to RM (87%, P=0.01), which translated into a lower proportion of high FLIPI patients (46% vs. 52% in OBS vs. RM, respectively; P=0.003). The induction regimens were as follows: R-CHOP in 70% and 83%, R-COP in 18.6% and 10.7%, R-bendamustine 1% and 4%, R-fludarabine-based in 4% and 1% and others in 5% and 1% in RM and OBS, respectively. The EOI remission status was assessed 61 days (median) after the last IC dose with CR/CRu/PR rates of 65%/9%/26% and 65%/6%/29% in OBS and RM, respectively (P=0.14). The median time from EOI response to the first RM dose was 48 days (range 0-371 days), 89% of the pts have started RM within 120 days. The median number of RM doses given was 8 (range, 1-36), with 85% of patients receiving 8-12 doses of RM. After a median follow-up of 10.4 yrs (OBS) vs. 6.0 yrs (RM); P

Description: We and others have shown that deregulation of microRNAs (miRNAs) is associated with the biology of B cell malignancies, including regulation of B cell proliferation and survival (Musilova & Mraz, Leukemia, 2015). We focused on studying miRNAs that associate with the aggressiveness of FL and its transformation to diffuse large B cell lymphoma (DLBCL). First, we analyzed the expression of 380 miRNAs (TaqMan Arrays, ABI) in 8 paired primary samples of FL that subsequently transformed to DLBCL. We identified statistically significant changes (P1.8) in the expression of 5 miRNAs. The most significant change was the down-regulation of miR-150 (~5 fold, P=0.01). Similarly, we observed significantly reduced miR-150 levels in an independent cohort of non-paired samples of FL before vs. after transformation to DLBCL, and miR-150 was significantly less expressed in de novo DLBCL in comparison with FL. MicroRNA miR-150 is of particular interest as we have shown that its expression determines BCR signaling propensity in chronic lymphocytic leukemia (CLL) B cells, and low levels associated with worse survival (Mraz et al., Blood, 2014). Therefore, we analyzed miR-150 expression in a cohort of 89 FL samples. We noticed that miR-150 expression was lower in samples from patients with a FLIPI score ≥3 (P=0.03), and with high Ki67 positivity (〉20%; P=0.003). Moreover, FL patients with low miR-150 levels (

Description: INTRODUCTION: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse. METHODS: We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age 〉70 years at diagnosis were selected. RESULTS: Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences. First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases. We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively. CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival. Disclosures Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.

Description: Abstract 4138 Background: 18F-FDG-positron emission tomography (PET) is a powerful tool for imaging of various lymphomas. Follicular lymphoma (FL) is the most common indolent lymphoma with usually slow progressive course, where growing is dependent on accumulation of cells with defect in apoptosis. In spite of its indolent nature, FL belongs to tumours with high 18F-FDG avidity. Semi-quantitative evaluation of PET activity can be defined as a standard uptake value (SUV max). Up to now, it is unclear, why FL is so highly 18F-FDG avid and whether SUV max can be of some prognostic value. Aims: We tried to correlate PET activity defined as SUV max with grade, tumor growth activity (Ki67), and prognosis using progression free survival (PFS). FL has, however, generally low proliferative activity. Therefore, other cells are expected to be responsible for 18F-FDG avidity in this disease. We selected suitable cells of “microenvironment”, and tried to correlate their numbers wit SUV max. Methods: Patients with newly diagnosed FL having PET with defined SUV max were included in this retrospective study. Diagnosis of FL including grading (grade 1–3) was confirmed by experienced hematopathologist on original lymph node samples and proliferation activity was evaluated by immunostaining with Ki67. In 25 cases, material was available and tissue microarrays (TMA) were done; populations of CD34 (endothelial marker), CD3 (global T-lymphocytes), CD8 (cytotoxic lymphocytes), FOXP3 (T-regulatory lymphocytes), CD23 (follicular dendritic cells) and CD68 (lymphoma associated macrophages) were evaluated. Ki67 as well as numbers of non-malignant elements were given in % of positive cells. Lymph node samples chosen for TMA were taken in our institution only, to avoid interlaboratory variability. Results: Data from 73 FL patients of stage II-IV were analyzed. Median age was 57 (31-76) years, and grading distribution was as follows: grade 1, 2 and 3 were observed in 40, 21 and 12 patients. Median follow up of the whole group was 45 months (1-73). PET activity defined as SUV max had median 7,8 (0-22,2), proliferation activity measured by Ki67 (n=53) ranged between 1,5-80% with median 25%. SUV max did not seem to correlate with grade or Ki67; moreover, SUV max did not predict course of follicular lymphoma in terms of PFS. No differences in gender, age or FLIPI were observed between subgroups with high and low SUV max. Additionally, 25 samples were available for TMA and subpopulations of microenvironment were evaluated. Although the number of samples was limited, we observed a tendency of positive correlation between amount of CD34+ cells (angiogenesis marker) and CD68+ (lymphoma associated macrophages) with SUV max (using cut off 8,0). Unfortunately, statistical significance could not be reached in these subpopulations (p 0.11 and 0.13). Surprisingly, we could identify strong negative correlation between number of interfolicullary localized CD8+ cells (cytotoxic lymphocytes) and SUV max using cut off 8 and 9 (p 0.02 and 0.003). Conclusions: Our data support the assumption, that proliferation activity, although various in FL, seems have nothing to do with 18F-FDG avidity. On the contrary, we observed strong correlation of CD8+ cells and SUV max and certain tendency that cells involved in angiogenesis (CD34+) and inflammatory response (CD68+) may influence SUV max as well. Based on our pilot results, we suggest that the microenvironment gives global 18F-FDG activity in FL. The microenvironment, however, is a mixture of various cells, and that could be the reason why SUV max does not seem to be a prognostic tool in this disease. Our preliminary results require confirmation by further research. Disclosures: No relevant conflicts of interest to declare.