Inwards, David J.

Introduction: Waldenström macroglobulinemia (WM) is characterized by circulating monoclonal IgM and bone marrow infiltration with lymphoplasmacytic lymphoma (LPL) cells. Presently, there is limited data to guide prognosis or treatment options of WM based on the proportion of lymphocytes or plasma cells in the LPL population on the pathology. In this study, we aim to look at differing clinical features and outcomes of patients with WM based on the plasma cell (PC) percentage in the diagnostic bone marrow biopsy. Methods Patients with WM seen at Mayo Clinic, Rochester, MN between January 2001 and December 2017, with a bone marrow biopsy and a corresponding serum free light chain (FLC) examination at diagnosis of WM were included. The percentage of lymphocytes and PCs in the marrow biopsy was determined based on morphology ± immunohistochemistry. On immunohistochemistry, CD138 and/or MUM-1 positivity was used to quantify PCs, whereas CD20 and/or PAX5 were used to quantify lymphocytes. Patients with ≥10% PC component in the lymphoplasmacytic (LPL) cells on bone marrow biopsy were considered to have WM with excess plasma cells (WMEPC), while those with <10% PCs were considered to have lymphocytic WM (LWM). Continuous variables were compared using Wilcoxon test and categorical variables were compared using Chi square test or Fisher's exact test. Time-to-next therapy (TTNT) was defined as the period from initiation of first line therapy to start of second line therapy or death due to any cause before second line therapy. Time-to-event analyses were conducted using Kaplan Meier method. Results: Of 228 evaluable patients, 147 (64%) had ≥ 10% PCs in the initial marrow biopsy. The median follow-up was 3.4 years (95% CI: 2.3-4.3 years) for LWM and 4.3 years (95% CI: 3.4-4.8 years) for WMEPC (p=0.33). The baseline characteristics of WMEPC versus LWM are depicted in Table 1. Patients with WMEPC had lower bone marrow involvement by LPL (30%) compared to LWM (60%; p<0.001) at diagnosis, but the rate of symptomatic hyperviscosity was higher in WMEPC during the disease course (Table 1). The TTNT was shorter for WMEPC [2.6 years (95% CI: 1.8-4.5 years)] compared to LWM [4.5 years (95% CI 3.2-8.2)], although it did not reach statistical significance (p=0.09, Figure 1). There was a trend towards shorter OS for WMEPC [Not reached (95% CI 7.2- NR)] compared to LWM [10.7 years (95% CI 7.3 -12.1 years); p=0.28], Figure 2. Of the 228 patients, 79% (n=182) had data available for systemic therapy. The rate of PR or better with frontline therapy was higher in rates in LWM compared to WMEPC (61 % vs 42% p=0.02, Table 1). Among WMEPC cohort, patients receiving either a proteasome inhibitor (PI)-based or an immunomodulatory (IMiD)-based combination as frontline therapy (n=16) had higher rates of partial response or better (68%) compared to non-PI/non-IMiD based therapy (n=114), p=0.04. Conclusion: WM with excess plasma cells at diagnosis is associated with a trend towards shorter TTNT and OS compared to WM with <10% plasma cells in the lymphoplasmacytic population at diagnosis. Our preliminary data shows higher rates of partial response or better with the use of PI/IMiD based therapy, but the small cohort size limits the strength of this finding which needs to be validated externally. Disclosures Ansell: Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Affimed: Research Funding. Gertz:Spectrum: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Prothena: Honoraria; Alnylam: Honoraria; Ionis: Honoraria. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Dispenzieri:Alnylam: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy. Lacy:Celgene: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Kapoor:Janssen: Research Funding; Cellectar: Consultancy; Glaxo Smith Kline: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria.

Abstract Background: Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoma with a heterogeneous disease course. For nearly a decade, the International Prognostic Scoring system (IPSS), requiring 5 variables (platelet count, hemoglobin, age, Beta 2 microglobulin and immunoglobulin M size) has been used to prognosticate patients with active WM. In this study, we attempt to propose a simplified prognostic model for patients with active/symptomatic WM. Methods: All patients with active WM diagnosed between 01/01/1996 and 12/31/2017 and evaluated consecutively at Mayo Clinic, Rochester were included in the study after Institutional Review Board approval. Active WM was defined as ≥10% marrow infiltration with lymphoplasmacytic cells plus monoclonal IgM of any size requiring systemic therapy. The follow up and overall survival (OS) were calculated from the time of active WM until date of last follow up or death. Baseline parameters at active disease were used to assess prognostic factors for OS using a univariate followed by a multivariate (MV) Cox regression analysis. Independent variables on the MV analysis were given a score proportional to their risk ratios (RR). All time-to-event analyses were performed using the Kaplan-Meier method and the survival curves were compared using log-rank test. Discriminatory ability of the IPSS and the currently proposed prognostic system was assessed using Harrell's concordance index wherein a higher c-statistic is associated with a better discriminatory ability. Results: We identified 889 patients with active WM. The median follow up was 8.2 years (95% CI: 7.5-9 years). The baseline characteristics of the patients are shown in Table 1. At the time of diagnosis of WM, 16% of patients had previously documented MGUS and 16% patients had smoldering (asymptomatic) WM. The course of WM was complicated by systemic amyloidosis in 8% (n=69), transformation to high-grade lymphoma in 4% (n=38), symptomatic hyperviscosity in 13% (n=118), myelodysplastic syndrome in 2% (n=17) and Bing-Neel syndrome in 1.4% (n=12) of patients. Of the patients tested, cryoglobulinemia was present in 17% (n=48), cold agglutinin disease in 34% (n=43) and Coombs positive hemolytic anemia in 9% (n=34) patients. The median OS was 10.6 years (95% CI: 9.7-11.4 years). The factors affecting OS are shown in Table 2. While the patients' MYD88L265P mutation status was not found to be prognostic for OS, age >65 years [RR 1.8 (95% CI: 1.2-2.8); p=0.01], LDH > upper limit of normal [RR 2.5 (95% CI: 1.3-4.6); p=0.003] and serum albumin <3.5 g/dL [RR 1.6 (95% CI: 1.1-2.5); p=0.02] were independently prognostic. Owing to comparable RRs, each of these were assigned a score of 1 point and a prognostic model with a minimum score of 0 and maximum score of 3 was constructed. A score of 0 was considered as low risk WM and 1 as intermediate risk WM. The patients with scores of 2 and 3 were analyzed together to form the high risk cohort due to comparable OS for these two groups. The patient outcomes based on this prognostic model are depicted in Figure 1. Using the new prognostic model (n-=341), the median OS for the low risk group (n=71, 21%) was 14.6 years (95% CI: 9 years- not reached) compared to 11 years (95% CI: 8.1-14.7 years) for intermediate risk (n=140, 41% ) and 7.2 years (95 % CI: 5.4-10 years) for the high risk group (n=130, 38%), p<0.0001. The data for the IPSS-WM were available in 319 patients in the entire cohort. The OS for low risk IPSS (n=56) was 14.6 years (95% CI: 12.1 years-NR), 15.6 years (95% CI: 8.3-18.5 years) for intermediate risk IPSS (n=131) and 9.1 years (95% CI: 6.8-11.2 yeas) for the high risk IPSS group (n=132; p=0.009). Among the 220 patients having data for IPSS-WM as well as our proposed model, the current three variable model held its prognostic significance (p=0.0004). The Harrell's c-index was 0.647 (95% CI 0.592-0.702) for our prognostic model and 0.58 (95%CI: 0.521-0.638) for IPSS-WM. Common frontline treatment comprised of rituximab monotherapy (n=277, 33%), rituximab with alkylator or purine analog combination (n=255, 30.5%) and other therapies, including alkylators/purine analog monotherapy, ibrutinib, proteasome inhibitors, etc., in 37% patients. Conclusion: A simpler, clinically useful, risk stratification model based on age, serum albumin and serum LDH with a potentially higher discriminatory value than IPSS-WM may be used to prognosticate patients with WM. This model requires external validation. Disclosures Ansell: Pfizer: Research Funding; Affimed: Research Funding; Celldex: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Merck & Co: Research Funding; Regeneron: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Gertz:Abbvie: Consultancy; Prothena: Honoraria; Medscape: Consultancy; annexon: Consultancy; Amgen: Consultancy; Alnylam: Honoraria; Teva: Consultancy; janssen: Consultancy; Physicians Education Resource: Consultancy; Ionis: Honoraria; spectrum: Consultancy, Honoraria; celgene: Consultancy; Research to Practice: Consultancy; Apellis: Consultancy. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lacy:Celgene: Research Funding. Dingli:Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding. Kumar:Takeda: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding.

Abstract Backgroud. The treatment landscape of mantle cell lymphoma (MCL) has significantly changed in last decades. Improvement in diagnosis and understanding of disease biology has been coupled with emergence of new therapeutic options, including targeted agents. While MCL outcome data comes primarily from clinical trials (CT), the impact of therapeutic advances on pattern of care (POC) and outcome in MCL in the general population is not well characterized. This study sought to characterize changes in pattern of care and outcomes of patients with MCL in a prospective observational series in the rituximab era. Methods. The study included consenting adult patients with newly diagnosed MCL that were prospectively enrolled into the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource, from 09/01/2002 to 06/30/2015. Demographic, clinical and prognostic factors were abstracted, and all patients were actively followed for re-treatment, relapse and death. Since bendamustine-rituximab (BR) regimen starting to be used in 2010, we defined patients enrolled from 09/01/2002 to 12/31/2009 as era 1 and those enrolled 01/01/2010 to 06/30/2015 as era 2. Baseline characteristics and outcomes, evaluated in terms of event free survival (EFS), overall survival (OS) and cause of death, were analyzed and compared between the two eras identified. Results. 348 patients with newly diagnosed MCL were enrolled. Five patients had no available data for front-line treatment and were excluded. The analysis was thus conducted on 343 patients: 169 patients were diagnosed in era 1 with a median follow-up of 131.2 months vs. 174 in era 2 with a median follow-up of 58.9 months. Baseline clinical characteristics and MIPI score were similar across the two eras ( Table 1). Frontline induction treatment was significantly different in the two eras. BR use was 0 vs 49 (28.2% ), R-CHOP/CHOP like regimen in 89 (52.7%) vs 45 (25.9%), high-dose cytarabine (HiDAC)-based therapy in 1 (0.6%) vs 28 (16.1%), intensified regimens (HyperCVAD) in 16 (9.5%) vs 8 (4.5%), other regimens (including R-cladribine, R-fludarabine-mitoxantrone, rituximab monotherapy) in 35 (20.7%) vs 13 (7.5%) patients in era 1 vs era 2 respectively. Non-systemic treatment (observation, surgery or radiation only) was performed in 25 (14.8%) vs 31 (17.8%), while 9 (8%) vs 12 (7.7%) patients were enrolled in clinical trials, in era 1 vs era 2 respectively. Autologous stem cell transplantation (ASCT) as consolidation of first line treatment or use of Rituximab maintenance was not different between Era 1 and Era 2. Among the entire cohort of 343 MCL patients, 3y-EFS and 3y-OS were 51.9% (95% IC 46.7-57.6) and 73.5 (95% CI 68.8-78.4), respectively (Figure 1). 3y-EFS was 45.9% (95% CI 39.0-54.1%) vs 58.4 (95% CI, 51.2-66.6%) in Era 1 vs Era 2 (HR 0.69 (0.51-0.92), p=0.006), 3y-OS was 70.9% (95% CI, 63.4-78.1%) vs 76.1% (95% CI, 69.7-83.1%) in Era 1 vs Era 2 (HR 0.87 (0.61-1.24), p=0.26), respectively (Figure 1). In a univariate analysis, high risk simplified MIPI was prognostic of lower EFS and OS in both the era groups. Conclusion. The BR regimen entered front line therapy of MCL resulting in decline of R-CHOP use in the MER. While rates of ASCT remain similar over the two eras, high dose cytarabine usage in induction therapy has increased. While POC in MCL continue to evolve, the introduction of bendamustine and high-dose citarabine based regimens resulted in an improvement in EFS but not OS in this observational cohort-based analysis. Findings in this study are important for design and planning of future clinical trials incorporating novel agents in induction therapy of MCL. Figure 1. Figure 1. Disclosures Cohen: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

Abstract Background: Limited data exist regarding histological transformation in patients with Waldenström macroglobulinemia (WM). In this study, we present the disease characteristics, outcomes and risk factors for histological transformation in WM. Methods: Patients with WM seen at Mayo Clinic, Rochester, MN between January 1996 and December 2017 were included. Patients with aggressive non-Hodgkin lymphoma in the setting of WM were considered to have transformation. Univariate analysis for comparing baseline characteristics of transformed versus non-transformed WM was performed using Wilcoxon, Fisher's exact and Chi square tests, as appropriate. Multivariate analysis was performed using logistic regression analysis. Cox proportional hazard method was used to assess the impact on time-to-transformation. All time-to-event analyses were calculated by the Kaplan-Meier method. Results: Of 1014 patients with WM, 42 patients (4.1%) developed histological transformation. The median follow-up for the entire cohort was 9.5 years (95% CI: 8.8-10.5 years). The cumulative probability of transformation was 2.3% at 5 years, 5.3% at 10 years and 8.5% at 15 years from diagnosis of WM, respectively. There was no difference in the 5-year cumulative probability of transformation in patients with WM diagnosed between 1996-2000 (2.1%), 2001-2005 (2.9%), 2006-2010 (2.7%) and 2011-2015 (3.8%), p=0.61.The disease characteristics, laboratory parameters and histology at transformation are outlined in Table 1. In patients with DLBCL histology (n=39), Revised-International Prognostic Index was calculable in 28 patients, with 50% (n=14), 46% (n=13) and 4% (n=1) of DLBCL belonging to poor, good and very good risk groups, respectively. For DLBCL histology, 18 patients were classifiable using Hans algorithm into germinal center B-cell (GCB) type (n=3, 17%) and non-GCB type histology (n=15, 83%). The median lines of therapy received prior to transformation for the entire cohort was 2 (range 0-9), with 5 (11%) patients not having received any therapy for WM before transformation. Number of lines of alkylator-based therapy used prior to transformation [median 1 line (range 0-4)] was comparable to that used in patients in whom WM did not occur [median 1, (range 0-6); p=0.78]. The median time-to-transformation from diagnosis of WM was 4.8 years (95% CI: 2.6- 6.8 years). Overall survival (OS) from transformed disease was 3.2 years (95% CI 1.1-3.9 years). The 10-year OS of patients with WM who transformed was lower (46%) compared to patients without transformation (60%) with a trend towards statistical significance (p=0.08), Figure 1. The MYD88L265P mutation status was available in 333 patients in the entire cohort (22/42 pts in the transformed cohort and 311/972 in the non-transformed cohort. Of the 22 patients in the transformed WM cohort, 13 (59%) exhibited MYD88WT genotype and 9 (41%) exhibited MYD88L265P genotype. The risk of transformation was higher in patients with MYD88WT status [Odds ratio 6.3 (95% CI: 2.6-15.5); p<0.0001]. Additionally, serum lactate dehydrogenase (LDH) was higher at diagnosis of WM in patients who transformed, Table 2. On multivariate analysis, MYD88WT status remained an independent predictor of disease transformation [p=0.003; odds ratio 10 (95% CI: 2.1-48)]. On univariate Cox proportional hazard analysis for identifying predictors of time-to-transformation, only MYD88WT mutational status was associated with shorter time-to-transformation with a 5-year transformation rate of 15.5 % for MYD88WT versus 2.6 % with MYDL265P mutated patients [risk ratio 6.2 (95% CI: 2.5-16.4); p<0.0001]. Treatment-related details in the transformed cases were available for 37 (90%) patients; R-CHOP was the most common (41%) frontline therapy for transformation; 33% patients underwent autologous stem cell transplantation for transformed disease during their disease course. Conclusion: Histological transformation is an uncommon event in WM but confers poorer survival. MYD88WT genotype is independently associated with histological transformation a shorter time-to- transformation in patients with WM. Disclosures Ansell: Trillium: Research Funding; Pfizer: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Takeda: Research Funding; Celldex: Research Funding; Regeneron: Research Funding; Merck & Co: Research Funding; Bristol-Myers Squibb: Research Funding. Gertz:Apellis: Consultancy; Alnylam: Honoraria; spectrum: Consultancy, Honoraria; janssen: Consultancy; annexon: Consultancy; Prothena: Honoraria; Abbvie: Consultancy; Amgen: Consultancy; celgene: Consultancy; Teva: Consultancy; Medscape: Consultancy; Ionis: Honoraria; Research to Practice: Consultancy; Physicians Education Resource: Consultancy. Dingli:Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Lacy:Celgene: Research Funding. Kumar:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding.

Abstract Introduction. Vitreoretinal lymphoma (VRL) is a rare ocular malignancy. Diagnosis and optimal treatment remain a challenge for clinicians. We present clinical characteristics and outcome of a cohort of 69 patients affected by vitreoretinal diffuse large B-cell (DLBCL) lymphoma treated at Mayo Clinic over a 28-year period. Methods. We accessed the Mayo Clinic Lymphoma Data Base to identify all patients > 18 years old with VRL diagnosed between 01/01/1990 and 01/31/2018. Only patients with DLBCL, confirmed at pathological review, were included. Clinical characteristics, therapies, response, relapse patterns and follow up status were collected and analyzed in the cohort and in the different subgroups: primary (PVRL, localized only in eye at diagnosis) vs concurrent (CVRL) vs secondary VRL (SVRL). Chi-squared test, Fisher's exact test and Wilcoxon's signed-rank test were used for analysis. Failure-free survival (FFS), overall survival (OS), central nervous system (CNS) and eye relapse-free survival were analyzed according to Kaplan Meier method. Differences between subgroups were compared with log-rank test. Since the group of SVRL can be affected by a survivorship selection bias, it was investigated separately for the outcome analysis. Results. A total of 69 patients with vitreoretinal DLBCL were included. At diagnosis, 33 (48%) were PVRL, 18 (26%) CVRL (eye plus CNS (N=17) or systemic (N=1) disease) and 18 (26%) had SVRL (9 primary CNS lymphomas, 9 systemic at diagnosis, among which 4 were primary testicular lymphomas). Unilateral intraocular involvement was observed in 16 (23%) cases. Clinical characteristics are reported in Table I. At diagnosis, patients received a systemic treatment in 35 (50%, including high-dose systemic MTX (HD-MTX, N 14, 20%), MTR (HD-MTX, Temozolomide and Rituximab) (N 7, 10%) and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) with or without Rituximab (N 10, 15%)), combined systemic plus intraocular treatment in 15 (22%), local radiotherapy in 10 (14%) and intraocular therapy (intraocular injections of rituximab or MTX or steroids or a combination of these) in 9 (13%) cases. Systemic Rituximab, autologous stem cell transplantation (ASCT) and therapeutic vitrectomy/enucleation were performed in 36 (53%), 20 (29%) and 5 (7%) patients, respectively. The median number of treatments was 2 (range 0-10). Among PVRL and CVRL (N=51), median FFS, CNS relapse-free survival, eye relapse-free survival and OS were: 1.8 y, 4.9 y, 3.8 y and 4.1 y, respectively (Fig 1). Among PVRL they were: 2.6 y, not reached (NR), 5.2 y and 9.3 y, respectively. No CNS relapse occurred beyond 4 years in the PVRL subgroup. The median OS for patients diagnosed between 1990 and 1999, in contrast to 2000 and 2018 was 1.5 y vs 9.4 y respectively (p= 0.0002). OS was significantly higher in PVRL, as compared to CVRL (p= 0.04). Previous immunosuppression and poor performance status were predictive of worse outcome (p=0.04), while ASCT correlated with higher OS (p= 0.009). In PVRL, a combined systemic + intraocular therapy was associated with higher FFS (p=0.002) and CNS-relapse free survival (p= 0.003), but no difference in OS was observed. Among 18 SVRL, at a median follow-up of 1.1 y after vitreoretinal relapse, median FFS and OS were 0.3 y and 1.3 y, respectively. Systemic toxicities included 8 (11.6%) acute renal failures, 8 (11.6%) infections, and 3 (4.3%) hemorrhages. Intraocular toxicities included cataract in 11, vitreal detachment in 3 , ocular hypertension in 5, retinal vessel occlusion in 3 and keratitis in 2 cases. Of 69 patients, 39 (56.5%) died secondary to lymphoma (N=21, 53.8%), infectious toxicity (N=2, 5.2%), unrelated (N=3, 7.7%) or unknown (N=13, 33.3%) causes. Conclusions. VR DLBCL is a rare disease, which can occur as primary, concurrent with systemic, or in relapsed disease. OS over the decades has significantly improved. In PVRL, no late CNS relapses were observed, while late intraocular relapses can occur. A combined approach with intraocular + systemic HD-MTX based treatment at diagnosis was associated with a higher FFS and CNS-relapse free survival in PVRL and is recommended in bilateral involvement, even though no differences in OS were observed. Treatment consolidation with ASCT can be considered in cases with concurrent systemic disease. Further studies are needed to confirm these results and to better define the role of new drugs in treatment of this uncommon malignancy. Disclosures Witzig: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract Introduction: Our group (Porrata et al, BBMT 2016; 22: 1017-1023) previously published that the infusion of autograft natural killer (NK) cells correlates with survival post-autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) patients. A limitation of our previous study was the lack of killer-immunoglobulin-like receptor (KIR) analysis. Thus, we set up to investigate if the infusion of autograft activating and inhibitory KIR affects survival in NHL. Methods: From December 2007 to October 2010, 122 NHL patients participated in our Phase III clinical trial. A total of 111 patients finished the trail and samples were available for analysis. We analyzed the content of the autograft for inhibitory and activating KIR using flow cytometry analysis of each apheresis collection. Overall survival (OS) and progression-free survival (PFS) were analyzed from the date of transplant. Results: With a median follow-up of 82.8 months (range: 2.1-122.3 months), patients infused with an activating NKp30 (CD158b-CD337+) KIR ≥ 0.09 x 109 cells/kg experienced superior OS and PFS vs < 0.09 x 109 cells/kg: [OS: median was not reached vs 39.8 months, 5 years OS rates of 95% (95%CI, 56%-98%) vs 43% (95%CI, 22%-48%), p < 0.0001, respectively; and PFS: median was not reached vs 12.7 months, 5-years PFS rates of 77% (95%CI, 65%-86%) vs 13% (95%CI, 6%-24%), p < 0.0001, respectively]. Patients infused with the inhibitory KIR2DL2 (CD158b+CD337-) KIR < 0.066 x 109 cells/kg experienced superior OS and PFS vs ≥ 0.066 x 109 cells/kg : [OS: median was not reached vs 48.2 months, 5 years OS rates of 86% (95%CI, 75%-93%) vs 44% (95%CI, 31%-88%), p < 0.0001, respectively; and PFS: median was not reached vs 25.6 months, 5-years PFS rates of 62% (95%CI, 49%-74%) vs 31% (95%CI, 20%-44%), p < 0.0002, respectively]. We combined NKp30 and KIR2DL2 into NKp30/KIR2DL2 ratio. Patients infused with an NKp30/KIR2DL2 ratio ≥ 1.8 experienced superior OS (Figure 1) and PFS (Figure 2) vs < 1.8 : [OS: median was not reached vs 33.4 months, 5 years OS rates of 95% (95%CI, 86%-98%) vs 33% (95%CI, 21%-47%), p < 0.0001, respectively; and PFS: median was not reached vs 14.9 months, 5-years PFS rates of 76% (95%CI, 63%-85%) vs 14% (95%CI, 7%-27%), p < 0.0001, respectively]. Multivariate analysis revealed that the NKp30/KIR2DL2 ratio was an independent predictor for OS [HR = 0.03, 95%CI 0f 0.01-0.07, p < 0.0001] and PFS [HR = 0.17, 95%CI 0f 0.09-0.31, p < 0.0001]. Conclusion: The NKp30/KIR2DL2 ratio provides a platform to develop an immunocompetent autograft to improve clinical outcomes in NHL patients undergoing ASCT. Figure 1. Figure 1. Disclosures Ansell: LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Celldex: Research Funding; Takeda: Research Funding; Merck & Co: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding.

Abstract Background : Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor was approved for the treatment of Waldenstrom Macroglobulinemia (WM) in January, 2015 based on the results of a clinical trial of 63 previously-treated patients with WM. Data on outcomes with ibrutinib outside of clinical trials are limited. Methods : Medical records of patients with WM seen consecutively between 02/01/2015 and 06/01/2018 at Mayo Clinic, MN, FL and AZ were reviewed and those treated with ibrutinib at any point during their disease were included. Refractoriness to prior therapy was defined as disease progression on therapy or within 2 months of stopping treatment. The response rates were assessed by WM VI International Workshop Criteria. Adverse events were graded using National Cancer Institute Common Toxicity Criteria for Adverse Events (AEs) v4.03. All time-to-event analyses were performed from the time of initiation of ibrutinib. Results : Eighty patients [previously treated, n=67 (84%), treatment-naïve, n=13 (16%)] received ibrutinib for active WM. Median follow-up was 18 months (95% CI: 12-19) and the median overall survival (OS) was not reached (NR) (95% CI: 27-NR) for the entire cohort at the date of last follow-up. The median age was 67 years (range: 50-88) and the median ECOG performance score was 1 (range: 0-3) at the time of ibrutinib initiation. Median lines of therapies prior to ibrutinib for the previously-treated patients was 2 (range: 1-9) and 35 patients (44%) had received ≥3 prior lines of therapy. Of the 80 patients, 52 patients (43 previously treated, 9 treatment-naïve) had data for response assessment. The baseline characteristics and laboratory parameters at initiation of ibrutinib are outlined in Table 1a and prior therapies are mentioned in Table 1b. Overall response rate (ORR) was 90% (100% in patients with ibrutinib as primary therapy and 88% in salvage therapy setting); major-response rate (MRR) was 77%. Median time to first and best response was 2.1 months (95% CI: 1.5-3.5) and 5.4 months (95% CI: 3.5-13), respectively. Other clinically relevant endpoints and AEs related to ibrutinib therapy are outlined in Table 2 and 3, respectively. The median time-to-next therapy was 33 months (95% CI: 28-NR). At last follow-up, 25 (32%) patients had discontinued ibrutinib therapy. The reasons for discontinuation was progression (n=8), elevated liver enzymes (n=4), cognitive changes (n=1), inability to achieve better than MR (n=1), atrial fibrillation (n=3), consolidation with autologous stem cell transplantation after PR with ibrutinib (n=1), transition to hospice care due to progressive head and neck cancer (n=1), infection in lower extremity (n=1), transformation to DLBCL (n=1), blistering rash which resolved after ibrutinib discontinuation (n=1), obscure GI bleed that resolved after ibrutinib discontinuation (n=1), fatigue (n=1) and for unclear reasons recorded as treatment intolerance (n=1). Following discontinuation of ibrutinib, 21 patients received salvage therapy. Of these, data regarding the response to salvage therapy was available in 9 (43%) patients (VGPR=2, PR=3, SD=3 and progressive disease=1); median PFS from the salvage therapy following ibrutinib discontinuation was 18 months (95% CI: 2-25). Of the 4 patients who were not treated following ibrutinib discontinuation; 1 elected hospice care due to concurrent head and neck cancer progression, and the other 3 patients elected to be monitored off therapy (one had achieved SD and two had PR from ibrutinib). Fourteen patients were evaluable for IgM rebound following ibrutinib discontinuation. Of those, 5 (36%) had sudden increase in IgM level [median: 158% from the IgM level after ibrutinib discontinuation (range: 22%-1368%)] within a median of 2 months (range: 1-3 months) and 1 patient required plasmapheresis for symptomatic hyperviscosity. Four of 5 patients received salvage therapy between 0-15 months. At last follow-up, 11 patients (14%) had died of whom 3 were on ibrutinib at the time of death [CNS involvement, (n=1), causes unrelated to WM, (n=2)]. Conclusions : Ibrutinib is an effective agent in WM patients with MYD88L265Pmutation. Our data regarding outcomes in non-trial setting appear comparable to the results observed in the pivotal clinical trial. Hematologists should be aware of unique ibrutinib associated toxicities and clinically relevant IgM rebound phenomenon following abrupt discontinuation of ibrutinib. Disclosures Ailawadhi: Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy. Gertz:janssen: Consultancy; Prothena: Honoraria; Medscape: Consultancy; Teva: Consultancy; celgene: Consultancy; annexon: Consultancy; Alnylam: Honoraria; Physicians Education Resource: Consultancy; spectrum: Consultancy, Honoraria; Apellis: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Ionis: Honoraria; Research to Practice: Consultancy. Kumar:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lacy:Celgene: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dingli:Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding.

Abstract PURPOSE Urgency to initiate therapy has to be weighed against the time required for screening and consenting to enroll a patient onto a clinical trial. Exclusion of patients with rapidly progressive or symptomatic disease may lead to selection of patients with less aggressive disease. We recently identified that a short diagnosis to treatment interval (DTI) is associated with adverse clinical factors and inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) (Maurer et al, JCO 2018); shorter time to treatment was also found to be associated with outcome in other aggressive lymphomas, including mantle cell lymphoma (MCL), in the National Cancer Database (Olszewski et al, BJH 2018). Here we assess the association of DTI with clinical variables and outcome in MCL from an observational cohort with validation in patients enrolled on an NCTN clinical trial. PATIENTS AND METHODS Newly diagnosed patients with MCL were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER), now a subcohort of the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study. Patients initially managed with observation were excluded. DTI was defined as the time in days from date of first lymphoma-containing biopsy to the initiation of therapy. Associations of DTI with clinical factors and outcome were examined using a 14 day split based on the previous MER study of DTI in DLBCL. Odds ratios (OR) and Cox model hazard ratios (HR) are reported. Outcome was assessed using event-free survival (EFS) where events were defined as progression/relapse, initiation of new anti-lymphoma therapy, or death due to any cause. A validation cohort was assembled from patients enrolled in CALGB (Alliance) clinical trial 50403. Protocol therapy was high dose chemotherapy with autologous hematopoietic stem cell transplantation (ASCT) consolidation and post-ASCT rituximab followed by bortezomib as either consolidation or maintenance. DTI was defined as time from diagnosis to study registration and outcome was assessed using progression-free survival (PFS) as defined on the clinical trial. RESULTS 271 patients with MCL enrolled in the MER from 2002-2015 and initiated treatment within 100 days of diagnosis. Median age at diagnosis was 64 years (range 36-76), 211 (78%) were male, and 92% were stage III-IV; MIPI was Low (41%), Intermediate (36%) and High (23%). Induction therapy was R-CHOP based (50%), B-R based (16%), HyperCVAD based (8%), 2-CDA based (11%), and other (15%). Median EFS of the cohort was 41 months (95% CI: 34-46). Median DTI was 26 days (IQR: 14-38) and 28% enrolled within 14 days of diagnosis, exhibiting a longer DTI than DLBCL patients enrolled in the MER during the same time period. Short DTI (0-14 days) was associated with adverse clinical factors including ECOG PS 2-4 (OR=5.74, 95% CI: 2.51-13.1, p<0.0001), elevated LDH (OR=2.30 95% CI: 1.25-4.22, p=0.0072), and higher MIPI score (OR=1.48, 95% CI: 1.04-2.07, p=0.025) but was not significantly associated with age, sex, B-symptoms, or stage (all p>0.30). Short DTI was also associated with inferior EFS (HR=1.78, 95% CI: 1.27-2.49, p=0.0008) which remained significant after adjusting for MIPI score (HR=1.72, 95% CI: 1.23-2.41, p=0.0016). In the validation cohort, 144 patients enrolled on 50403 within 100 days of diagnosis from 2006-2010. Median age at diagnosis was 59 years (range 29-69), 77% were male, and 97% were stage III-IV; MIPI was Low (51%), Intermediate (31%) and High (17%). Median PFS of the cohort was 84 months (95% CI: 50-109). Median DTI was 35 days (IQR: 22-46) and 11% enrolled within 14 days of diagnosis. Short DTI (0-14 days) was associated with PS (OR=9.00, 95% CI: 1.18-69.0, p=0.034) and) higher MIPI score (OR=2.09, 95% CI: 1.08-4.04, p=0.029) but not elevated LDH (OR=1.27, 95% CI: 0.43-3.74, p=0.66). Short DTI was associated with inferior PFS (HR=2.21, 95% CI:1.19-4.09, p=0.011) which remained clinically significant after adjusting for MIPI score (HR=1.85, 95% CI: 0.98-3.47, p=0.056). CONCLUSION A short diagnosis-to-treatment interval is strongly associated with adverse clinical factors and poor outcome in newly diagnosed MCL in the MER. Clinical trials are encouraged to facilitate enrollment of patients with short DTI to avoid potential selection bias. Support: U01 CA195568, P50 CA097274, U10CA180821, U10CA180882; ClinicalTrials.gov Identifier: NCT00310037 (CALGB 50403) Figure. Figure. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Kaplan:Bayer Pharmaceuticals: Consultancy. Cohen:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Takeda: Research Funding. Martin:Gilead: Consultancy; Kite: Consultancy; Seattle Genetics: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy; Bayer: Consultancy. Kahl:Abbvie: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Acerta: Consultancy; Juno: Consultancy; Celgene: Consultancy; Genentech: Consultancy; Seattle Genetics: Consultancy; CTI: Consultancy; ADC Therapeutics: Consultancy. Bartlett:ImaginAB: Research Funding; Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Merck & Co: Research Funding; Forty Seven: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Affimed: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding. Leonard:Karyopharm: Consultancy; Biotest: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Novartis: Consultancy; AstraZeneca: Consultancy; Juno: Consultancy; BMS: Consultancy; Sutro: Consultancy; MEI Pharma: Consultancy; Genentech/Roche: Consultancy; Celgene: Consultancy; Gilead: Consultancy; United Therapeutics: Consultancy.

Abstract The peripheral blood absolute lymphocyte count (ALC) on day 15 after autologous stem cell transplantation (ASCT) has been shown to be an independent predictor for overall survival (OS) for many malignancies including acute myelogenous leukemia (AML), breast cancer, multiple myeloma (MM), primary systemic amyloidosis, and Hodgkin’s and non-Hodgkin’s lymphoma (NHL). A recent report (Dean et al. BMT2005; 36, 1049–1052) suggested that infused autograft dendritic cells (DC) affect survival post-ASCT in NHL. Thus, DC recovery at day 15 post-ASCT was assessed and correlated with OS. Preliminary data from an ongoing prospective study of 28 NHL patients post-ASCT are reported. Absolute DC at day 15 was analyzed by four color flow cytometry using antibodies to CD3, CD14, CD16, and CD19. In this approach lymphocytes and DCs were initially gated by their similar forward and side light scatter characteristics; DCs were then identified as cells in this gate that lacked staining for the lymphocyte antigens CD3, CD16, and CD19 and the monocyte antigen CD14. The percentage of antigen negative cells cells in the lymphocyte gate was then multiplied by the coincident peripheral blood absolute lymphocyte to determine the absolute DC count. Survival was then analyzed using the Kaplan-Meier method. With a median follow-up of 18 months, patients recovering a DC of 10 cells/μl or above experienced superior median OS versus those who did not (not reached vs 21 months, p < 0.02, Figure 1). This study shows that an immunocompetent immune system at day 15 (not only ALC recovery, but also DC recovery) correlates with survival in NHL patients undergoing ASCT. Figure Figure

Abstract Abstract 85 Background: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma (NHL) with a highly variable natural history. Clinical variables describing either patient- or tumor-specific characteristics, many of which are included in the Follicular Lymphoma International Prognostic Index (FLIPI), are used to risk-stratify patients at the time of diagnosis. However, characteristics of non-malignant cells present within the tumor microenvironment provide important prognostic information. For example, both immunohistochemistry and gene expression profiling studies demonstrate that lymphoma-associated macrophages (LAMs) are prognostically important in FL. As LAMs are monocyte-derived, we sought to determine whether the absolute monocyte count (AMC) obtained from a CBC at diagnosis is an adverse prognostic factor in FL. Methods: Consecutive patients with FL who were evaluated and treated at the Mayo Clinic, Rochester between 1998 and 2007 were considered for study participation. Study approval was granted by the Mayo Clinic Institutional Review Board. The primary objective of the study was to determine the significance of the AMC, obtained at the time of diagnosis from a standard complete blood count with differential, in predicting overall survival. The secondary study objective was to determine whether the AMC is an independently significant prognostic factor when compared with the FLIPI. Results: The median follow-up was 4.2 years (range: 2 months to 11 years) for the 355 patients included in this study. At diagnosis, 43%, 34% and approximately 23% of patients were classified as low-, intermediate- or high-risk by the FLIPI. The median AMC at diagnosis was 510/μL, with 8% of patients presenting with an absolute monocytosis. At diagnosis, 45% of patients were initially observed, 42% received combination chemotherapy or immunochemotherapy alone, while the remaining 13% underwent surgery or radiation. The AMC was evaluated as both a continuous and dichotomized variable on univariate analysis. The optimal cut-point for the AMC was determined to be 570/μL by ROC analysis and was used when analyzing the AMC as a dichotomized variable. A relative elevation in the AMC was associated with inferior overall survival, whether analyzed as a continuous or dichotomized variable, with hazard ratios (HR) of 1.002 (HR per unit change in AMC; 95% confidence interval 1.001–1.002; p=0.0002) and 3.4 (95% confidence interval 2.0–6.0; p<0.0001), respectively. The median OS for patients with an AMC <570/μL at diagnosis has not been reached, whereas a median OS of 10.2 years (95% confidence interval 7.8–11.2 years; p<0.0001) was observed for those patients with an AMC ≥570/μL. For comparison, median OS has not been reached for high-risk patients identified by the FLIPI. Among those patients who were initially observed, the median time to progression (TTP) was 31 months (95% confidence interval 25–37 months) for those with an AMC <570/μL at diagnosis. In contrast, patients with an AMC ≥570/μL experienced a significantly shorter TTP following initial observation, with a median TTP of 18 months (95% confidence interval 8–28 months; p=0.03). When adjusting for prognostic factors included in the FLIPI on multivariate analysis, the association between the AMC as a dichotomized variable and survival remained significant with a HR of 2.6 (95% confidence interval 1.5–4.6; p=0.001). When the FLIPI alone (high vs. low/intermediate) was analyzed on multivariate analysis, the AMC remained an independent predictor of survival (p<0.0001). Furthermore, the AMC provided additional prognostic information when superimposed upon the FLIPI. For example, a subset of patients classified as high-risk by the FLIPI were observed to have an OS comparable to low/intermediate risk patients identified by the FLIPI upon further risk-stratification by the AMC, with a 6-year OS of 80%. In contrast, high-risk FLIPI patients with an AMC ≥570/uL were observed to have a median OS of 4.2 years (95% confidence interval 2.7–7.2) and 6-year OS of 47%. Conclusions: The AMC is associated with overall survival in FL and is independent from the FLIPI on multivariate analysis. While the AMC did not appear inferior to the FLIPI in identifying high-risk patients, it may be most helpful when used in conjunction with the FLIPI. These results further support the central role of nonneoplastic myeloid-lineage cells in FL biology. Disclosures: No relevant conflicts of interest to declare.