Strouse, Christopher S

7573 Background: While most patients (pts) with follicular lymphoma (FL) usually have favorable outcomes, those with refractory disease after first-line anti-CD20 based immunochemotherapy (IC), or progression within 24 months of diagnosis (POD24) have higher risk of premature death. There are no standard approaches for treating this vulnerable group and studies testing novel agents are ongoing in this setting. We sought to investigate clinical practice treatment choices and efficacy for pts with POD24 that align with eligibility criteria for the randomized SWOG1608 which compares IC with novel agents in this population. Methods: This was a multicenter observational cohort study from the LEO Consortium. Eligible pts had grade 1-3a FL diagnosed between 1/1/2002 and 2/1/2019, and initiated therapy after POD24 to first-line bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based IC. Observation, radiotherapy, or rituximab monotherapy were permitted prior to IC and pts with transformation prior to the subsequent therapy after IC were excluded as per S1608. Outcomes of interest were overall and complete response rate (ORR/CR), progression-free survival (PFS), and overall survival (OS). Results: We identified 196 eligible pts with early progression to IC (39% antiCD20 Benda; 61% antiCD20 CHOP) who received subsequent therapy. Median age at post IC treatment was 57 years, 78% grade 1-2 FL. Treatments for pts with POD24 included CHOP- or Benda-based in 31%, salvage/hematopoietic stem cell transplant (HSCT) in 27%, novel therapies in 10% (including phosphatidylinositol 3-kinase inhibitors), antiCD20 monotherapy in 9%, and lenalidomide-based treatment in 8% (table); 21% of pts were treated on clinical trials. Across all treatments, ORR (CR) was 63% (37%) (95% CI: 55-70). At a median follow up of 6.2 years, 2 year PFS was 22% (95% CI: 17%-29%) and 5 year OS was 71% (95% CI: 65-79). Outcomes by regimen are shown in the table. Conclusions: Pts with FL experiencing POD24 following first-line IC are treated heterogeneously, with many pts still receiving IC as subsequent therapy. Despite modest CR rates and low 2-year PFS, 5-year OS appear to be improving compared to historical outcomes. This supports the ongoing need to investigate novel treatments in this population. [Table: see text]

PURPOSE: This study assessed the long-term quality of life (QOL) of patients with aggressive lymphoma subtypes treated with autologous hematopoietic cell transplant (autoHCT) compared with those without history of transplant. METHODS: Patient-reported QOL measures were prospectively gathered from patients enrolled in the Iowa/Mayo Specialized Program of Research Excellence Molecular Epidemiology Resource cohort with aggressive lymphoma subtypes. QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy–Fatigue Scale, State-Trait Anxiety Inventory (STAI), and Profile of Mood States instruments and with a numeric rating scale for overall QOL and spiritual QOL. The autoHCT group and no HCT groups were compared at 3 years (FU3) and 6 years (FU6) after lymphoma diagnosis. RESULTS: In total, 980 patients with lymphoma (106 autoHCT and 874 no HCT) diagnosed between 2002 and 2013 were included for analysis. The mean FACT-G total score was similar in the autoHCT and no HCT groups at FU3 (89.9 v 90.1, P = .64) and also at FU6 (91.5 v 89.6, P = .44). No differences between the autoHCT and no HCT groups were identified in the FACT subscales. The STAI identified lower anxiety in the autoHCT group by mean STAI1 (state) at FU3 (30.1 v 33.4, P < .01) and by mean STAI2 (trait) at FU6 (30.1 v 33.5, P = .02). No other clinically meaningful differences were identified between the two groups using the other QOL instruments. CONCLUSION: Patients remaining in remission at 3 and 6 years after diagnosis had a high level of QOL with no significant differences associated with history of treatment with autoHCT.

BackgroundAlthough many patients with follicular lymphoma (FL) undergo routine radiographic surveillance during their first remission, no consensus exists on the modality, duration, frequency, or need for routine imaging studies. The authors retrospectively examined the effect of surveillance imaging on relapse detection and overall survival (OS) in patients with FL.MethodsPatients with newly diagnosed FL who had a response to induction therapy were identified from the Lymphoid Malignancies Enterprise Architecture Database (LEAD) at Emory University and from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic. Patients were evaluated for both relapse and method of relapse detection (ie, clinical concerns vs radiologic detection through surveillance imaging in an asymptomatic patient).ResultsOf 148 patients in the LEAD cohort, 55 (37%) relapsed, and the majority (n = 35; 64%) of relapses were detected clinically. In the MER cohort, 63 of 177 relapses (54%) were detected clinically. There was no significant difference in OS from the date of diagnosis between the 2 methods of relapse detection in the LEAD (hazard ratio [HR], 0.61; 95% CI, 0.13‐2.94; P = .54) and MER (HR, 1.02; 95% CI, 0.47‐2.21; P = .96) cohorts. Similarly, there was no significant difference in OS from the date of relapse between the 2 methods of relapse detection in the LEAD (HR, 0.47; 95% CI, 0.10‐2.27; P = .35) and MER (HR, 1.02; 95% CI, 0.47‐2.21; P = .96) cohorts.ConclusionsThese findings suggest a limited role for routine surveillance imaging in patients with FL who complete front‐line therapy. Future studies should evaluate which patients may benefit from a more aggressive surveillance approach and should explore novel methods of relapse detection.

Background: Observation or "wait and watch" (W/W) strategy remains a viable option in the rituximab era for asymptomatic, stage II-IV, low-tumor burden patients with FL grade 1-2, 3A. Studies to date both in pre and post rituximab era have not shown an overall survival benefit from immediate treatment in such low-risk patients.To improve our understanding and to better counsel FL patients on W/W strategy, we sought to estimate the incidence of treatment initiation at landmark time points in our prospectively observed cohort from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). We further evaluate the association between the presence of GELF criteria (MER treatment criteria) at diagnosis and initiation of treatment patterns, transformation rates and cause of death in FL patients managed by W/W. Methods: FL patients on W/W strategy were identified from MER of the University of Iowa/Mayo Clinic Lymphoma SPORE. From 2002-2015, consecutive patients with newly diagnosed FL were offered enrollment. Patients were managed per treating physician and followed prospectively. Baseline clinical and pathological data were abstracted using a standard protocol. Cumulative incidence estimates of treatment initiation for follicular lymphoma were calculated using transformation to large cell lymphoma (as the first event) and death due to any cause as competing risks. Transformation was defined based on biopsy-proven disease. Patients were retrospectively considered to meet treatment criteria at diagnosis if they had the presence of any GELF criteria components per available abstracted data in the MER database. Not all GELF criteria were prospectively assessed and captured for all patients, and thus the MER treatment criteria utilized here will be conservative for formal GELF assessment. Results: A total of 401 FL patients were identified in MER on W/W strategy. Baseline characteristics for W/W patients showed a favorable profile such as normal LDH (89%), low and intermediate FLIPI score in 48% and 35% respectively, no B symptoms (97%), low tumor burden (&lt;4 nodal groups) in 72%, and GELF positive vs. negative in 36% and 64% respectively. At a median follow up of 8 years (IQR 5.9-12), 64% initiated treatment for FL only. Cumulative incidence estimates of treatment initiation at sequential time points were calculated from the initiation of observation (Table1&2). At diagnosis, the likelihood of treatment initiation was 15%, 26%, and 42% in the next 1, 2, and 5 years. The incidence of treatment initiation decreased over time as patients remained treatment-free after diagnosis (Figure 1A [blue curve]). Patients that met MER treatment criteria had increased rates of therapy initiation (33.2% vs. 21.9%) in the next two years and untreated transformation to large cell lymphoma [red curve] (8.7% vs. 4.5%) during the next 5 years (Figure 1B). Despite this, the rate of lymphoma related death at 10 years was similar between groups (met treatment criteria = 6.2% vs. 7.1%) (Figure 1C, [green curve]). Discussion: The longer duration of W/W strategy suggests a decreasing need for treatment over time. We provide time point estimates, which would be helpful for counseling patients. Of note, long-term continuous oncologic assessment and follow-up is necessary since approximately 66% of patients in this mature cohort initiated treatment by 8 years median follow up. MER treatment criteria at diagnosis identified patients with higher rates of transformation and therapy initiation in the first two years but did not identify those with worse lymphoma specific survival. Identification of biological differences in patients with early vs. late or no progression is a critical next step in understanding outcomes in W/W patients. Disclosures Ansell: Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; ADC Therapeutics: Research Funding; Trillium: Research Funding. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding. Wang:Incyte: Research Funding; Innocare: Research Funding; Novartis: Research Funding. Witzig:MorphSys: Consultancy; AbbVie: Consultancy; Incyte: Consultancy; Acerta: Research Funding; Karyopharm Therapeutics: Research Funding; Immune Design: Research Funding; Spectrum: Consultancy; Celgene: Consultancy, Research Funding. Maurer:Morphosys: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding. Nowakowski:NanoString: Research Funding; Kite: Consultancy; Seattle Genetics: Consultancy; Kymera: Consultancy; Celgene/BMS: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees.

INTRODUCTION Complete staging via bone marrow assessment is standard of practice for most newly diagnosed non-Hodgkin lymphoma (NHL) patients, though the methods and patterns of bone marrow assessment vary in clinical practice. The 2014 Lugano Classification recommends that in diffuse large B cell lymphoma (DLBCL), positron emission tomography-computed tomography (PET/CT) alone can designated advanced-stage disease in many, but not all cases. For most other NHL subtypes, obtaining bone marrow biopsy (BMB) remains recommended. We aimed to assess clinical practice patterns of marrow assessment and the performance of PET/CT in the clinical setting. METHODS The Lymphoma Epidemiology of Outcomes (LEO) cohort is a prospective cohort from 8 academic medical centers. All patients were enrolled in the cohort within 6 months of diagnosis, and prospectively followed. Patients with lymphoma enrolled in the cohort between July 2015 and June 2017 were included for study. Baseline clinical characteristics at diagnosis, whether BMB and/or PET/CT were performed, and the result of these assessments were extracted from the database. Bone marrow involvement on PET/CT was abstracted via review of radiology reports. No central review of images was utilized. RESULTS In total, 3,251 patients were included, consisting of the following subtypes: DLBCL (n=1,098), follicular lymphoma (FL n=730), mantle cell lymphoma (MCL n=302), T-cell lymphoma (TCL n=278), marginal zone lymphoma (MZL n=269), other NHL (n=505) and composite lymphoma (n=69). Other clinical characteristics are shown in table 1. Staging BMB was obtained in 78% of patients, PET/CT was obtained in 56%, both BMB and PET/CT were obtained in 46% while neither were obtained in 9% (table 1). There were significant differences in lymphoma subtype between patients having any bone marrow assessment vs no bone marrow assessment (p<0.0001). MCL (96%) and DLBCL (94%) most frequently had any bone marrow assessment, while MZL was least frequently assessed (84%). Patients undergoing any bone marrow assessment had higher median lactate dehydrogenase (247 U/L vs 206 U/L, p=0.0002). Among the 8 enrolling medical centers, the frequency of bone marrow biopsy at diagnosis ranged from 53% to 86%, and the frequency of PET/CT at diagnosis ranged from 34% to 94% (p<0.0001, table 1). Among patients with DLBCL who had positive bone marrow by either PET/CT or BMB (N=107), 41% (44/107) were positive by BMB only, 19% (20/107) were positive by PET/CT only, and 40% (43/107) were positive by both. Figure 1 shows results of similar analyses for FL, MCL, MZL, and TCL. Using BMB as a gold standard for marrow involvement, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for marrow assessment in DLBCL is 49%, 90%, 68% and 91%, respectively. Data for other subtypes are shown in table 2. Patients undergoing both PET/CT and BMB had lower median LDH (231 U/L vs 254 U/L, p=0.0032) than those undergoing one or neither assessments. CONCLUSION Overall, 91% of all patients with newly diagnosed NHL had bone marrow assessments via either PET/CT, BMB or both. The significant variation in the frequency of BMB and PET/CT use among the 8 centers reflects a lack of clear consensus on staging practices regarding bone marrow assessment. The sensitivity of PET/CT for detection of marrow involvement was less than 50% across all subtypes. It is possible the sensitivity of PET/CT could be improved via a centralized review process of the images, as is performed in some clinical trials, however practical approaches for implementing such reviews in clinical practice have not been developed. Between 92-100% of all positive bone marrows were detected by BMB, except in cases with DLBCL in which 19% of positive bone marrows were missed by BMB but detected by PET/CT. Thus, in our analysis, BMB more reliably captured marrow involvement that PET/CT in all subtypes in which both assessments were performed. However, neither PET/CT nor BMB alone were able to identify all cases of bone marrow involvement and use of both modalities may be necessary in cases where marrow involvement would have clinically important implications. Disclosures Rutherford: Juno Therapeutics Inc: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria. Kahl:ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; TG Therapeutics: Consultancy; BeiGene: Consultancy. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Friedberg:Acerta: Other: Data & Safety Monitoring Committee; Bayer: Honoraria, Other: Data & Safety Monitoring Committee. Casulo:Celgene: Research Funding; Roche: Other: Travel, accommodation, expenses; Gilead: Honoraria, Other: Travel, accommodation, expenses. Cohen:Astra Zeneca: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Hutchison: Research Funding; Gilead/Kite: Consultancy; Bristol-Meyers Squibb Company: Research Funding; LAM Therapeutics: Research Funding; UNUM: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Genentech, Inc.: Consultancy, Research Funding. Nastoupil:TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Spectrum: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Bayer: Honoraria. Flowers:Denovo Biopharma: Consultancy; Spectrum: Consultancy; National Cancer Institute: Research Funding; Optimum Rx: Consultancy; Burroughs Wellcome Fund: Research Funding; Acerta: Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; Millenium/Takeda: Research Funding; Celgene: Consultancy, Research Funding. Cerhan:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; NanoString: Research Funding. Martin:Sandoz: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; I-MAB: Consultancy; Janssen: Consultancy.