Advanced Follicular Lymphoma Patients Research Articles

Clinical features and outcomes of patients with follicular lymphoma grade 3A: A real-world study in single center.

e19058 Background: Follicular lymphoma (FL) was classified into three grades based on the number of centroblasts (FL1-2, FL3A, and FL3B). Guidelines suggest that FL1-2 should be treated according to the treatment recommendations for classical FL. FL3B is usually treated as diffuse large B-cell lymphoma (DLBCL).There is no consensus yet on the management of FL3A. In order to explore the relationship between clinical features and outcomes of FL3A, we conducted this study. Methods: We conducted a retrospective study of newly diagnosed FL patients who were admitted to our hospital from January 2013 to December 2022. The data were collected from the hospital electronic medical record system, including but not limited to: demographic characteristics, pathological information, clinical features at diagnosis, treatment, and efficacy evaluation. The survival curve was calculated through Kaplan-Meier method and compared with Log Rank test.The prognostic factors of PFS was compared by COX regression analysis. Results: There were 253 FL3A patients admitted, accounting for 27.55% of all FL patients. After screening, a total of 223 FL3A patients were included in this study. Among 223 patients, the male to female ratio was close to 1:1; The median age is 57 years old. At diagnosed, 33 patients in early stage and 190 in advanced stage. Among advanced patients, 144 had no treatment indications according to the GELF criteria. 86.1% (192/223) of patients received systemic treatment, with the majority of rituximab contained regimens. The overall response rate (ORR) was 96%, and 62.9% of patients who responded to chemotherapy received maintenance therapy with CD20 monoclonal antibody. A median follow-up of 41 months, with an estimated 5-year OS of 91.3% and 5-year PFS of 73%. The PFS of advanced FL patients treated with RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was significantly longer than that of non-RCHOP regimen patients (P<0.05). The PFS of patients receiving maintenance treatment was better than that of those not (P<0.05). Conduct prognostic analysis on advanced FL3A patients. Univariate analysis showed that treatment plan selection, maintenance of treatment, PET scan of FDG metabolic maximum uptake value (SUVmax), Ki-67, lactate dehydrogenase (LDH), white blood cell count (WBC), IgA, IgM, all significantly affected PFS; Multivariate analysis shows SUVmax ≥ 15 and platelet count<100 × 109/L and LDH>210U/L are all correlated with poor PFS. Conclusions: This study found that FL3A accounts for 27.55% of all FLs, with a median age of 57 years old and mostly in the advanced stage. FL3A has a long survival period, with a 5-year PFS of 73%. COX regression analysis showed that SUVmax, platelet count, and LDH were all associated with PFS in advanced FL3A patients.Those may explore new clinical prognosis prediction models.

Maintenance and consolidation strategies for patients with untreated advanced follicular lymphoma: A systematic review and network meta-analysis of randomized trials.

The emergence of novel and efficient antibody maintenance approaches has provided more options for post-induction treatment of advanced follicular lymphoma (FL), and further comparisons are required to determine the most clinically beneficial regimen. The authors conducted a systematic review and meta-analysis to evaluate the maintenance or consolidation strategy. The authors performed two independent searches in PubMed, Web of Science, the Cochrane library databases, Scopus, and Embase for randomized controlled trials (RCTs) evaluating maintenance or consolidation therapy in untreated FL patients. Extracted data included the clinical characteristics, treatment regimen, progression-free survival (PFS), overall survival (OS), and adverse effects. They then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. The authors screened 1515 records and identified 13 eligible RCTs that assessed nine different regimens in 5681 advanced FL patients. Reconstructed individual survival data presented that obinutuzumab had the highest effect sizes and certainty of the evidence for PFS (hazard ratio, 0.43; 95% confidence interval, 0.22-0.79) and tolerability compared with observation. However, no benefit was observed in patients according to the OS, regardless of which regimen was taken. Considering other regimens, although an extended course of rituximab maintenance and consolidation therapies presented PFS benefits compared with standard rituximab maintenance, they were also associated with higher toxicity. Although obinutuzumab and rituximab maintenance treatment improved PFS significantly, its clinical benefit requires further validation in larger populations. Furthermore, because few trials informed each treatment comparison, research is needed to refine the understanding of this complex and rapidly evolving treatment landscape.

MRD Monitoring By Euroclonality IGH Based NGS Approach Predicts Outcome in Follicular Lymphoma Patients Lacking a Conventional BCL2::IGH Marker: A Substudy from the Fondazione Italiana Linfomi (FIL) FOLL12 Trial

Background. Despite durable clinical responses achieved by chemo-immunotherapy in follicular lymphoma (FL) patients, most of them eventually relapse. Actually, minimal residual disease (MRD) analysis based on the detection of BCL2::IGH rearrangement by PCR is the most widely used and standardized approach, able to early identify patients at high risk of disease reappearance. Nevertheless, this tool fails the molecular marker definition in up to 45% of cases, hampering the disease monitoring in a large group of patients. In the last decade, the continuous improvement of next-generation sequencing (NGS) techniques allowed to introduce these novel tools for MRD monitoring in some hematologic diseases, as acute lymphoblastic leukemia and multiple myeloma, thus reducing PCR limitations and increasing the number of patients eligible for MRD. Nonetheless, applications of NGS tools for MRD detection in FL are still scant. Aims. Therefore, we tested the feasibility of the EuroClonality (EC) IGH-based NGS approach [Brüggeman, Leukemia 2019] to identify novel molecular markers suitable for MRD monitoring in the context of the large prospective trial “FOLL12” (EudraCT: 2012-003170-60) by the Fondazione Italiana Linfomi (FIL), where 57% of patients were already studied for MRD by classic PCR methods targeting the BCL2::IGH rearrangement.[Luminari, JCO2022] Methods. Advanced FL patients received upfront treatment with either R-CHOP or BR, followed by a combined PET/MRD response-based maintenance with rituximab. Bone marrow (BM) samples were centralized to the FIL MRD Network for standardized MRD analysis. Baseline gDNA of “no marker” patients was screened by IGH-based NGS using EC-IGH two-steps PCR approach in the EuroMRD certified lab of Torino university; then MRD was monitored in those patients harboring a IGH clonal marker at baseline by one step EC-IGH method. The identification of baseline clonotypes and MRD clones was performed by ARRest/Interrogate tool. Results. 343/786 enrolled patients (43%) lacked a conventional BCL2::IGH marker and 161/343 (47%) showed morphologic BM lymphoma infiltration: of these, 124 (77%) had an available BM baseline sample for IGH screening and were thus included in the analysis. Overall, IGH clonotypes suitable as novel molecular markers were identified in 75/124 patients (60%), of which 73 monoclonal and 2 biclonal. Of this series, 47 patients had centralized a BM sample for MRD analysis at end of induction. Median age of this subset was 59 years (33-81), 53% were female, all were Ann Arbor stage IV, 34% were FLIPI intermediate and 43% high risk, respectively. Moreover, 56% received R-CHOP and 44% BR as induction treatment, resulting in a 79% CR rate and 89% MRD negativity rate (in line with the results of the general trial population). PFS at 3 years for this series was 69%: however, the 5 patients who scored MRD positive (MRD+) showed statistically significant worse PFS at 3 years than MRD negative cases (22% vs 73%, respectively, p=0.0069, Figure 1). Notably, 4 out of 5 MRD+ patients experienced POD24. Focusing on biclonal cases, one presented superimposable MRD trends between clones (both achieving MRD negativity), while in the other both clones remained MRD positive but showing one Log difference between them. Interestingly, only one of the two clones showed a MRD increase in the following timepoint (6 months after end of induction), heralding the clinical relapse subsequently occurred at month 12 (Figure 2). On the other hand, no IGH clonotype was identified in the first 17 patients who were screened for a novel MRD marker despite the absence of BM infiltration. Conclusions. The first data on the large-scale application of NGS-based marker screening tools in FL patients lacking a conventional BCL2::IGH marker for MRD enrolled in a prospective clinical trial showed that the EC IGH-based NGS approach was able to provide a new molecular marker in 60% of patients with evidence of BM infiltration (that means about the 28% of “no marker” FL patients); importantly, this approach was predictive of worse PFS for MRD+ cases. Overall, these data are promising for the wide employment of novel, effective MRD monitoring tools, able to recover more than one fourth of FL patients lacking a conventional molecular marker and so, by combining conventional and NGS-based techniques, potentially rising the percentage of MRD evaluable cases up to at least 70% cases.

Baseline PET Metabolic Tumor Volume Predicts Outcome in Advanced Follicular Lymphoma Patients Who Received First-Line Immunochemotherapy but Not Those Treated with Lenalidomide-Rituximab in the Phase III Relevance Study

Introduction The prognostic value of total metabolic tumor volume (TMTV) at diagnosis in follicular lymphoma (FL) remains debated. Its impact was reported for patients treated mostly with Rituximab (R)-CHOP chemotherapy without R maintenance (FOLLCOLL study, Meignan et al, J Clin Oncol. 2016; 34(30):3618-3626) but manual TMTV assessment was not confirmed as prognostic in the GALLIUM trial where most patients had bendamustine and anti-CD20 antibody maintenance (Barrington et al, Blood 2018; 132(Suppl 1):2882). There is no data on the prognostic value of TMTV in chemo-free regimens such as the immunomodulatory combination of lenalidomide and rituximab (R2). Here, we investigated the prognostic value of baseline TMTV for FL patients with previously untreated advanced FL included in in the phase 3 RELEVANCE trial comparing R2vs R-chemo with both regimens followed by rituximab maintenance therapy (NCT01476787 and NCT01650701). Methods TMTV was computed on baseline PET/CT using the 41% SUVmax method. To separate high and low TMTV, we tested the previously published cut-off of 510cm3 (Meignan et al. J Clin Oncol. 2016; 34(30):3618-3626). Survival was estimated using Kaplan Meier curves. Analyses were performed on the total PET-evaluable population (n=406/1032) with 196 pts on the R2 arm and 210 pts on the R chemo arm, because baseline PET was not mandatory in this trial. Results Clinical baseline characteristics of PET evaluable patients were similar to the overall trial population for age, Ann Arbor stage, bone marrow infiltration, LDH, beta 2 microglobulin and FLIPI, and well balanced between the two treatment arms. After a median 6.5 years follow-up, 5y-PFS was 67.6%, 5y-OS was 93.5%, with no significant difference between the two arms. Median baseline TMTV was 284 cm3 in the whole cohort (Q1-Q3; 144-553) : 274 cm3 (129-526) in the R2 arm and 288 cm3 (148-562) in the R chemo arm (p=0.579). Overall, patients with TMTV > 510 cm3 had higher Ann Arbor stage (p<0.001), more extra nodal sites (p<0.001), more frequently elevated beta 2 microglobulin (p<0.001), higher FLIPI (p=0.002) and FLIPI2 scores (p<0.001). High TMTV was significantly associated with an inferior PFS (p=0.0121) and POD 24 (p=0.0014) but not OS (p=0.247). Patients with a high TMTV (n=111, 27%) had a 5-year PFS of 53.9% (CI 95% 43.6-63.1) vs 70.5% (CI 95% 64.7-75.6) for low TMTV patients. By contrast, bulk as measured by CT (either >6cm or >7cm) was not prognostic of PFS (p=0.978 and p=0.661 respectively). When testing FLIPI with TMTV both were independently associated with PFS (p=0.0119 and p=0.0379, respectively). When testing FLIPI2 with TMTV, only TMTV remained significant (p=0.2444 for FLIPI2, p=0.0285 for TMTV). The combination of FLIPI and TMTV stratified the overall population into 3 risk groups : patients with no risk factors had a 5y-PFS of 76.3% (n=162, 40% reference), declining to 63.4% for patients with 1 risk factor (n=180, 44%; HR=1.45 ;[1.01-2.06], p=0.042) and 47.1% (n=64, 16%; HR=2.15 [1.39-3.31], p<0.001) for patients with both. Although the interaction between TMTV and randomization arm was not statistically significant for PFS (p=0.31), the prognostic impact of TMTV appeared different between the two arms: a high TMTV was associated with a lower PFS in the R chemo arm (Figure 1 A: p=0.0093) whereas it was not significant in the R2 arm (Figure 1B: p=0.3369). Conclusion: Baseline TMTV was a strong prognostic factor independent of FLIPI or FLIPI2 status, in advanced FL patients treated with first-line immunochemotherapy followed by antibody maintenance but not R2. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Obinutuzumab Short Duration Infusion Is Preferred By Healthcare Providers and Has Minimal Impact on Patient-Reported Symptoms Among Patients with Untreated, Advanced Follicular Lymphoma

Obinutuzumab Short Duration Infusion Is Preferred By Healthcare Providers and Has Minimal Impact on Patient-Reported Symptoms Among Patients with Untreated, Advanced Follicular Lymphoma

Ten-Year Follow-up of Newly Diagnosed Follicular Lymphoma Patients Treated with Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) As First-Line Therapy in JCOG0203 Trial

[Purpose]Rituximab combined with chemotherapy has been established as a standard of care for patients with newly diagnosed advanced stage follicular lymphoma (FL), especially with high tumor burden. However, the best chemotherapy partner of rituximab remains unclear. Owing to inevitable relapse and succumbing to histologic transformation (HT), there are prerequisites for first-line treatment to improve the outcome of FL patients. To elucidate the long-term outcome of FL patients more than 10 years after treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line therapy in a prospective clinical trial, we report the 10-year follow-up results of the patients allocated to either R-CHOP arm in a randomized phase II/III trial (JCOG0203, NCT00147121), in which both arms of R-CHOP-21 and R-CHOP-14 showed almost equal survival.[Patients and Methods]Patients with untreated indolent B-cell lymphoma in advanced stages were assigned to the potential standard arm; six cycles of R-CHOP-21 or the experimental arm; R-CHOP-14 with G-CSF. Rituximab maintenance was not allowed (JCOG0203 Trial; Watanabe T, et al, J Clin Oncol 2011;29:3990). Histopathologic specimens from all 300 patients were reviewed by 3 hematopathologists. The primary endpoint of the study was progression-free survival (PFS). According to the planned analysis after 10 years following enrollment of the last patient, clinical event information was updated. PFS and overall survival (OS) were estimated by using the Kaplan-Meier method, and Hazard ratio (HR) and its confidence interval were estimated through the Cox proportional hazards model. The incidences of HT and secondary malignancies were analyzed by cumulative incidence function.[Results]From September 1st, 2002 to February 28, 2007, 300 patients were enrolled. The number of patients lost to follow-up within 10 years from randomization was 19 in all eligible patients. Ten-year PFS were 32.8% (R-CHOP-21) vs . 38.8% (R-CHOP-14), and 10-year OS were 80.9% vs . 84.7%, respectively in 299 eligible patients; namely, there were no differences. According to the Follicular Lymphoma International Prognostic Index, there were no differences found for either PFS or OS in any of the three risk groups.We identified only male sex (HR: 1.57, 95% CI: 1.16-2.12) as a significant, unfavorable PFS factor, and age (>60) (HR: 2.03, 95% CI: 1.19-3.45) and increased LDH (>ULN) (HR: 2.38, 95% CI: 1.27-4.43) as significant, unfavorable factors of OS.The proportion of FL was comparable between the arms (133 and 132 patients), and therefore, the combined analyses of the two arms were performed. In a total of 265 FL patients, 5, 8, and 10-year PFS were 46.2, 39.6, and 36.8%, respectively. Five, 8, and 10-year OS were 93.6, 86.7, and 84.4%, respectively (Figure 1).HT was diagnosed in 27 of the 248 FL G1-3a patients (10.9% [95% CI: 7.3-15.5]), including 10 HT diagnosed clinically by the data including steep elevation of LDH levels or high accumulation of FDG (defined by SUVmax) in PET imaging (63.0% of HT was proved by biopsy). The pattern of the HT accumulation slope was similar to those reported previously but slightly different from that of PRIMA Trial, which showed more than half of them occurred within the first one year of follow-up; the cumulative incidence of HT at 3, 5, 8, and 10 years after enrollment were 2.4% (95% CI: 1.0-4.9), 3.2% (95% CI: 1.5-6.0), 8.5% (95% CI: 5.4-12.4), and 9.3 % (95% CI: 6.1-13.4), respectively (Figure 2).The incidence of secondary malignancies in the 248 FL G1-3a patients at 10 years was 8.1% (95% CI: 5.1-12.0) [hematologic malignancies; 2.9%].[Conclusions]R-CHOP may reduce the incidence of HT compared with previous reports in the pre-rituximab era and did not increase a 10-year cumulative incidence of secondary malignancies in previously untreated FL patients, compared with published data. Although 10-year OS of advanced FL patients treated with R-CHOP without rituximab maintenance in the first-line setting was favorable, 10-year PFS was unsatisfactory. Dose-dense immunochemotherapy did not improve either PFS or OS in patients with indolent B-cell lymphoma. Therefore, the new treatments to deepen remissions and to prolong time to progression of FL patients are needed. [Display omitted] DisclosuresTobinai:Chugai/Roche: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria. Kinoshita:Chugai: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Jannsen: Honoraria; Kyowa Kirin: Honoraria; Bristol: Honoraria; Eisai: Honoraria; Takeda: Research Funding; Solasia: Research Funding; MSD: Research Funding. Yamaguchi:Eisai: Honoraria; Takeda Phamaceuticals: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharma: Honoraria; Nippon Shinyaku: Honoraria. Ando:Kyowa Hakko Kirin: Research Funding; Takeda Pharmaceutical: Research Funding. Ogura:Astrazeneca: Honoraria; Takeda: Consultancy, Honoraria; Mundipharma: Consultancy; Celltrion, Inc: Consultancy, Honoraria; SymBio: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; MeijiSeika Pharma: Consultancy. Tsukasaki:Chugai/Roche: Honoraria; Zenyaku Kogyo: Honoraria; Mundypharma: Research Funding; HUYA: Honoraria; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Kyowa-Kirin: Honoraria.

Similar Efficacy and Safety of CT-P10 and Reference Rituximab in Patients with Advanced Stage Follicular Lymphoma: Updated Phase III Study Results

Background: CT-P10 is an approved biosimilar to the innovator rituximab (RTX) from many countries including European Union based in part on the pharmacokinetics (PK) equivalence and comparable efficacy in patients with previously untreated advanced follicular lymphoma (FL) when treated with rituximab plus cyclophosphamide, vincristine and prednisone (R-CVP) as an induction therapy (Coiffier B et al. ASH 2016; Kim WS et al. ASCO 2017).Objective: We report here the updated efficacy outcomes including progression free survival (PFS), duration of response, overall survival (OS), as well as updated safety profile of CT-P10 compared to RTX in advanced FL patients with median follow-up duration of 23 months including the Maintenance Period with rituximab monotherapy.Methods: These results were derived from an ongoing randomized and double-blind study in patients with previously untreated advanced FL (NCT02162771). A total of 140 patients were randomized in a 1:1 ratio and 124 patients completed 8 cycles of R-CVP induction therapy. One-hundred twenty two patients (62 patients in CT-P10 group and 60 patients in RTX group), who showed response during the Induction Period, entered the Maintenance Period where a total of 12 cycles of rituximab monotherapy was to be administered every 2 months. The study was planned to continue until death or up to 3 years from the randomized date of the last patient. Kaplan Meier (KM) method was used to estimate PFS, duration of response, and OS.Results: Both groups had similar baseline characteristics; overall median age of 58 years, 55% female, 57% with FLIPI score ≥3, 100% with Stage III/IV, 18% with bulky disease (≥7cm) and 26% with B-Symptom.As of the cut-off date for investigator-assessed PFS, duration of response and OS, median follow-up was 23 months (range, 0.5-34) in the CT-P10 group and 22 months (range, 0.2-33) in the RTX group. The proportion of patients who had experienced relapse, disease progression or death from any cause was 22.9% (16/70) and 24.3% (17/70) for the CT-P10 and RTX groups, respectively. There was no significant difference between CT-P10 and RTX groups in PFS (log rank, p-value: 0.806) with 2-year PFS of 75.2% and 73.5%, respectively (Figure 1). In terms of sustained response, the proportions of patient who showed relapse or disease progression after achieving overall response (Complete Response, unconfirmed Complete Response, or Partial Response) were 19.4% (13/67) in CT-P10 group and 21.3% (13/61) in RTX group, and the KM curves showed no statistically significant difference between CT-P10 and RTX (log rank, p-value: 0.997) (Figure 2). Death from any cause were 5.7% (4/70) and 2.9% (2/70) in the CT-P10 and RTX groups, respectively. There was no statistically significant difference in OS (log rank, p-value: 0.464) between the CT-P10 and RTX groups with 2-year OS of 93.2% and 95.3%, respectively.Overall safety profile of CT-P10 was consistent with that of RTX (Table 1). A similar number of patients in each treatment group experienced at least 1 Treatment Emergent Adverse Events (TEAE) considered to be related to the study drug, infusion-related reaction, and infection. The proportion of patients with positive anti-drug antibody was also similar in both groups (4.3% [3/70] vs 5.7% [4/70] in the CT-P10 and RTX groups). Neither progressive multifocal leukoencephalopathy nor Hepatitis B virus reactivation was reported in either group.Conclusion: At the median follow-up duration of 23 months, the updated efficacy data in advanced FL patients demonstrated comparable PFS, sustained response and OS between CT-P10 and RTX. CT-P10 was also well tolerated and its safety profile was similar to that of RTX. The updated safety results did not reveal any trends or new signals noted in the patients treated with CT-P10. [Display omitted] DisclosuresKim:Mundipharma: Research Funding; Novartis: Research Funding; Kyowa-Kirin: Research Funding; Celltrion: Research Funding; Roche: Research Funding; J&J: Research Funding; Takeda: Research Funding. Buske:Roche: Honoraria, Research Funding; Bayer: Research Funding; Janssen: Honoraria, Research Funding. Ogura:MeijiSeika Pharma: Consultancy; Celltrion: Consultancy, Research Funding; Mundi Pharma: Consultancy; SymBio: Research Funding; Takeda: Honoraria; Cellgene: Honoraria. Coiffier:CELGENE: Consultancy, Membership on an entity's Board of Directors or advisory committees; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees; MORPHOSYS: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees. Lee:Celltrion, Inc: Employment. Kim:Celltrion, Inc: Employment.

Improving Treatment Strategies for Patients with Follicular Lymphoma: How to Translate Novel Study Data into Clinical Practice

Prof Bruce Cheson opened the symposium by highlighting the unmet needs for patients with follicular lymphoma (FL) and the potential application of prognostic scores, imaging techniques, and genomics to stratify patients. Ms Rosmarie Pfau detailed the challenges faced by patients with FL around the world, particularly a desire for improved quality of life (QoL) and effective treatments with less toxicity. Prof Mathias Rummel discussed modern methods of assessing FL risk and predicting treatment outcomes, particularly regarding endpoint selection for clinical trials. Dr Andrew Davies presented data from the GALLIUM study, showing that obinutuzumab-chemotherapy and maintenance is superior to rituximabchemotherapy and maintenance in untreated advanced FL patients, while Prof Gilles Salles provided insight into future options being developed for patients with FL.

Rituximab Maintenance for Advanced Follicular Lymphoma (FL) Patients - Comparison of Outcomes after First and Second Line Treatment in a Single Center Series

Standard approach to advanced stage FL patients in need of treatment is immunochemotherapy followed by rituximab maintenance (RM). Maintenance improves disease control after first line and overall survival in the relapse setting. The relative benefits of maintenance after first or subsequent treatment have not been directly compared.Purpose: To compare the clinical outcome of patients receiving RM after first-line treatment with those who received RM for the first time after second line.Patients and Methods: We retrospectively analyzed the outcomes (time to next treatment, TTNT, and progression free survival, PFS) of a single center series of advanced FL patients in remission after first or second treatment who received RM. Demographic and clinical characteristics before first or second induction (age, gender, FLIPI and FLIPI2) as well as induction chemotherapy, response rate, PFS and TTNT were retrieved from clinical charts. Patient characteristics at the beginning of induction were compared by Chi-squared test and time-to-event outcomes evaluated by the Kaplan Meyer method and compared by log rank test, with and without stratification for FLIPI; we calculated the adjusted hazard ratio controlled for FLIPI using Cox regression; p‹0.05 was considered significant.Results: Among 371 advanced FL patients diagnosed and treated in a single center between 2001 and 2013, we identified 83 (45% male) who responded to first or second induction and received RM between 2005 and 2015 (59 after first line - M1 group - and 24 after second line - M2 group; 375 mg/m2 every 2 or 3 months for 2 years, respectively). M2 patients were older than M1 (median age 63 versus 55 yo). Other characteristics before induction were similar between the two groups, including FLIPI (low 14% and 13%, intermediate 42% and 33%, high 42% and 42% for M1 and M2, respectively; p=0.93) and FLIPI2 risk group distribution (low 10% and 4% , intermediate 49% and 38%, high 36% and 38% for M1 and M2, respectively; p=0.62). Median time from diagnosis was 5.1 years in M2 patients; M1 patients were treated at a median of 1.9 months after diagnosis.First line treatment in the M1 group was mostly RCHOP (76%) while similar proportions of M2 pts received RCHOP (38%) and RCVP (46%) as second line. 20/24 of M2 pts (83%) had received Rituximab as part of first line treatment. CR/CRu rates after induction were comparable (48% and 42% in M1 and M2 pts respectively; p=0.17). After maintenance, with 13 pts not yet evaluable for response, ORR was 68% in M1 and 50% in M2 (p= 0.15). The frequency of CR/CRu was similar for first and second line patients (43% and 42% in M1 and M2, respectively) with 10/31 (32%) and 4/11 (36%) PR patients converting to CR after M1 and M2, respectively. At a median follow-up of 2.3 in M1 and 2.5 years in M2, relapse/progression occurred in 16 (27%) and 8 (33%) patients, respectively. A new treatment was started in 19% and 29% of patients in the M1 and M2 groups. Accordingly, TTNT after M1 (not reached) was significantly longer than after M2 (33.2 months), p=0.04. This difference was not significant in stratified analysis by FLIPI. However, when controlling for FLIPI, the hazard of subsequent therapy in M2 was twice as M1 (HR=2.1; 95% CI: 0.8-5.4). Two-year PFS was also superior in M1 (80% [95% CI 70-92%] versus 62% [95% CI 44-87%] in M2) although not statistically significant (p= 0.19). Indeed, there was a 50% increase in the risk of progression or death adjusted for FLIPI in M2 compared to M1 (HR=1.5; 95%CI: 0.6-3.8).Conclusion: In this series, although patients receiving RM both after first and second induction therapy benefited from the treatment, longer treatment-free intervals and disease control were seen in the first line setting. The benefits of repeating Rituximab maintenance have not been prospectively evaluated; in countries where economic constraints impose restrictions to its repeated use, our results suggest that advanced FL patients should preferentially receive RM after first line. DisclosuresSilva:Roche Pharmaceutics: Consultancy.

Risks and Benefits of Rituximab Maintenance in Elderly Patients with Advanced Follicular Lymphoma

Introduction: Based on the PRIMA trial (Lancet 2010; 377: 42-51), rituximab maintenance following induction rituximab-based chemotherapy is the standard of care in patients with advanced follicular lymphoma (FL) because it extended the 3-year progression free survival (PFS) from 58% to 75%, with a low rate of infection (<5%). However, this study was conducted in young patients (median age 57 years old) and the benefits and risks of the maintenance are unknown in elderly patients.Methods: We reviewed the clinical characteristics, outcome and complications of 62 advanced FL patients selected based on having successfully completed induction chemotherapy and initiated maintenance rituximab at the Jewish General Hospital between 2007 and 2014. The age cut off of ≥75 years old at the time of treatment was defined as "elderly". We compared characteristics of the two groups using the χ2 test and calculated PFS using the Kaplan-Meier method and log-rank test.Results: In total, 9/62 (15%) patients were "elderly" and 53/62 (85%) were "young", with median ages of 79 (75-87) and 55 (30-74) years old, respectively. Elderly patients had more adverse prognostic features compared to younger patients: B symptoms (4/9 vs 7/53, p=0.023), elevated lactate dehydrogenase (5/9 vs 9/51, p=0.013), lower hemoglobin (5/9 vs 3/52, p<0.001) and poor performance status (3/9 vs 1/53, p<0.001). The mean PFS was lower in elderly patients (25 months vs 65 months, p=0.05). The 3-year PFS in the young group was 80%. Toxicities were higher in the elderly group: grade 3-4 neutropenia (3/9 vs 5/53, p=0.05) and infections (5/9 vs 13/52, p=0.063).Conclusion: Elderly patients had more adverse prognostic factors and a significantly inferior PFS with rituximab maintenance compared to younger patients. The rates of infections were higher than those reported in the PRIMA trial. Maintenance rituximab may not benefit elderly patients with advanced FL. DisclosuresNo relevant conflicts of interest to declare.

Therapeutic Approach to Advanced Follicular Lymphoma at Diagnosis: An Argentinian Survey

Different treatment guidelines suggest that advanced follicular lymphoma (AFL) subjects should be treated only when meeting criteria treatment, such as GELF, are present. Conversely, when absent the watch and wait (W&W) approach is recommended. However, in our country, we had the impression that in real life, a high percentage of patients without the above-mentioned criteria were treated. With the purpose of unravelling the medical approach of AFL patients at diagnosis and subsequent evolution, the Lymphoma Subcommittee of the Argentinian Society of Haematology undertook this retrospective survey.Results: From years 2006 to 2014 305 patients from 23 institutions were included. GELF criteria were encountered in 62% of patients at diagnosis and all of them were treated with immunochemotherapy (ICT). Among the 116 (38%) patients without meeting GELF criteria (GELF negative group), in only 30 (26%) W&W was the approach chosen, while the rest received ICT. The survey questionnaire revealed that own assessment of the treating physician was the main reason for treating the GELF negative group. In the W&W group, 60% required ICT at a mean of 17 months, being 15% of them transformed to DLBCL at time of treatment. The 89% of cases (271/305) received ICT at some time; 66% R-CHOP, 29% R-CVP, and 5% other regimes. Patient median age receiving R-CHOP and R-CVP was 57 and 62 years (p<.01), respectively. Rituximab maintenance (RM) was added to ICT in 64% of cases. For the whole group, with a median follow up of 36 months, the overall survival (OS) was 95% and progression free survival (PFS) 68%. Comparing GELF negative and positive groups, PFS was better for GELF negative group, 87% vs 61% (p <.01). There was no difference in OS. Within the GELF negative group, OS was not different between patients treated at the time of diagnosis vs those in which a W&W approach was chosen.Conclusion: 1) When comparing with international reports, the percentage (62%) of patients with positive GELF criteria was higher at diagnosis. This fact may be due to delay in access to health care; 2) we found a remarkable discrepancy among guidelines recommendations and real life medical behaviour. Three out of four patients received treatment at diagnosis, when W&W ought to have been the guideline-recommended approach; 3) R-CHOP was the most used ICT scheme, while R-CVP was mostly reserved for the elderly. RM was indicated in the majority of patients, particularly after year 2011; 4) despite acknowledging the methodological limitations of this retrospective analysis, a high tumor mass (GELF positive) picture conferred a worse prognosis in term of PFS, while a W&W approach did not affect the OS for the GELF negative group. DisclosuresRiveros:Roche: Speakers Bureau.

90Y-ibritumomab tiuxetan followed by reduced-intensity conditioning and allo-SCT in patients with advanced follicular lymphoma

RIC HSCT is a potentially curative therapeutic option for patients with advanced FL but disease relapse remains the most common cause of failure. Radioimmunoconjugates administered prior to RIC allogeneic HSCT may enhance cytoreduction and allow more time for graft versus lymphoma effect to develop without the associated toxicity of a myeloablative HSCT. We performed a retrospective study to describe the outcomes of patients with relapsed, refractory or transformed FL who received 90Y ibritumomab tiuxetan followed by fludarabine and low-dose busulfan RIC allogeneic HSCT at the Dana-Farber Cancer Institute between 2006 and 2009, inclusively. Twelve patients were identified with a median age of 55 (40–66) years and a median number of lines of therapy of 5 (2–10). Two patients (17%) had transformed to a more aggressive histology and 5 (42%) had chemorefractory FL. Cumulative incidences of grade II–IV acute GVHD at 100 days were 17% (± 11%) and chronic GVHD at 12 months were 63% (±19%). Two-year non-relapse mortality was 18% (± 12%). Two-year OS and progression-free survival (PFS) were 83% (± 11%) and 74% (± 13%), respectively. This treatment is associated with favorable outcomes including acceptable rates of GVHD and relapse in advanced FL patients and warrants prospective studies.