Micallef, Ivana N.

Abstract Abstract 1222 Poster Board I-244 Background Survival for patients with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now update on outcomes of patients who have had at least 100 day follow up post ASCT. Baseline characteristics Between June, 2000 and January, 2009, 22 patients underwent ASCT for PCNSL. Median age at transplant was 50 years old (range 26-67). Median number of prior treatments 1 (range 1-3). Median time from diagnosis to transplant was 7.2 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0-3). Disease status at transplant: First CR 10 patients, later CR or PR 12 patients. Results Twenty-two patients underwent ASCT for PCNSL and have a minimum of 100 days follow-up. All patients received BEAM conditioning. Median follow up post-transplant was 30 months (range 3-107 months). Eight patients have relapsed at a median of 217 days (range 40-1349). Of the patients who relapsed, four have died of disease progression and the remaining four are alive after additional therapy. Median overall survival from diagnosis or transplant has not been reached. Median progression free survival from transplant was 70 months. Conclusions Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2-3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline secondary to radiation therapy in patients who are appropriate candidates. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 1540 Background: Diffuse Large B-cell Lymphoma (DLBCL) is the most common lymphoma in the western world. Outcomes have improved with the standard initial therapy of rituximab and anthracyline based chemotherapy (immunochemotherapy). However, 20–40% of patients will either fail to achieve remission or relapse following initial immunochemotherapy. Most relapses occur early, and long-term outcome of relapsed/refractory patients is generally poor despite salvage regimens and stem cell transplant. Traditionally, studies for DLBCL have been evaluated using progression-free and/or overall survival. However, the event rate in DLBCL slows significantly approximately 12–18 months after diagnosis, and late events are often due to competing (non-DLBCL related) risks, especially in older patients. Here we examine outcome of DLBCL patients based on their event status at 12 months. Methods: Newly diagnosed DLBCL patients were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER). Clinical data were abstracted from medical records using a standard protocol. Patients were actively followed for events (progression, re-treatment, or death due to any cause) and overall survival (OS). Event-free status at 12 months after diagnosis (EFS12) was assessed as a dichotomous variable. Cause of death was determined by medical record and death certificate review using prospectively determined definitions. Expected survival was based on age and sex matched survival using the Minnesota population death rates. Confirmation cohorts were from a Lyon, France hospital based registry and NCCTG clinical trial N0489. Results: 680 patients with newly diagnosed DLBCL and treated with rituximab + anthracycline based chemotherapy were enrolled in the MER from 2002 to 2009. The median age was 62 years (range 18–92). 53% were male. At a median follow-up of 59 months (range 8–116), 266 patients (39%) had an event and 188 patients (28%) died. 162 patients (24%) had an event in the first 12 months after diagnosis, comprising 60% of all events. Patients with an event in the first 12 months had poor survival with death almost exclusively due to disease (Figures 1a, 2a). In contrast, patients who were event-free at 12 months had comparable survival to the age and sex matched general population (Figure 2b) and were more likely to die of other causes than DLBCL (Figure 1b). Overall survival rates by EFS12 status were validated in patients from a French hospital-based registry (N=265) and the NCCTG N0489 clinical trial (N=87) with additional replication studies underway. Conclusions: DLBCL patients who are event-free at 12 months after diagnosis have an excellent prognosis with an overall survival similar to that of an age- and sex- matched general population and are more likely to die of other causes than DLBCL. This finding has implications for clinical management, new clinical trials, and follow-up testing in this patient population. In contrast, patients with an event within the first 12 months after diagnosis have a poor prognosis with almost all deaths secondary to DLBCL. EFS status at 12 months identifies patients with poor outcomes due to disease. This can be utilized as an endpoint in biologic studies and clinical trials to address early treatment failures. EFS status at 12 months should be incorporated into prognostic models to identify high risk patients in newly diagnosed DLBCL. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Absolute lymphocyte count (ALC) recovery is an independent prognostic factor for survival for different hematological malignancies treated with autologous stem cell transplantation. Recently, we reported superior overall survival (OS) in patients with follicular lymphomas that presented with a higher ALC (ALC ≥ 1 x 109/L) at diagnosis. The role of ALC at diagnosis on survival in T cell lymphomas is not known. Methods: All patients evaluated at the Mayo Clinic for T cell lymphomas from October 1984 until April 2005 were analyzed in the study. The primary objective of the study was to assess the role of ALC at diagnosis and survival in T cell lymphomas. ALC at diagnosis was obtained from the standard complete blood cell count (CBC). Results: 223 patients with T cell lymphomas were included in the study. The histology included: peripheral T-cell lymphoma-unspecified (40%), anaplastic large cell (13%), angioimmunoblastic (10%), angiocentric (4%), intestinal T-cell (2%), and other (31%). The median follow-up was 18.6 months (range: 1 month – 229 months [19 years]). The sample population included 60% male and 40% females with a median age of 60 years (15–90 years). The median ALC at diagnosis was 1.2 x 109/L (range: 0.04–6.7 x 109/L). ALC as a continuous variable was identified as predictor for OS in the univariate analysis (HR= 0.690, 95%CI: 0.542–0.862, p < 0.0006). ALC ≥ 1 x 109/L was selected as the dichotomized value because it yielded the maximum difference in survival by c2 analysis looking at different cut-point from 0.6 to 1.7 x 109/L that were included between the 25% and 75% quartiles. Univariately, ALC ≥ 1 x 109/L was also identified as a predictor for OS (HR = 0.682, 95%CL= 0.578–0.804, p < 0.0001). Patients (N = 122) with an ALC ≥ 1 x 109/L experienced superior survival compared to patients (N = 101) with an ALC < 1 x 109/L [median OS: 76.3 vs 10.6 months, respectively; and 5 years OS estimates of 53% vs 23%, respectively, p < 0.0001]. When ALC ≥ 1 x 109/L was compared to the international prognostic index (IPI), ALC ≥ 1 x 109/L remained an independent predictor for survival in the multivariate analysis (HR = 0.779, 95%CL: 0.655–0.925, p < 0.004). Conclusion: This study demonstrates ALC as an independent predictor for OS in T cell lymphomas, suggesting that the host immune system affects survival in this group of patients.

Abstract Abstract 1527 Interim Positron-Emission Tomography (PET-scan), as a functional imaging test for tumor activity, has been shown to be a predictor for progression-free survival (PFS) and time to progression (TTP) in classical Hodgkin lymphoma (HL). The peripheral blood absolute lymphocyte/monocyte ratio (ALC/AMC) at diagnosis, as a surrogate marker of host immunity (i.e., ALC) and tumor microenvironment (i.e., AMC), has been recently reported [Porrata et al, Hematologica 2012; 97(2): 262–9] and confirmed [Koh et al, Oncologist 2012; 17(6): 871–80] to be also a predictor for PFS and TTP in classical HL. Therefore, we evaluated the combination of ALC/AMC ratio at diagnosis and the interim PET-scan to further stratify the clinical outcomes of PFS and TTP in patients with classical HL. To participate in the studies, patients were required to be diagnosed, treated, and followed at Mayo Clinic, Rochester, Minnesota. The treatment consisted of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiation therapy. Patients were required to have an interim PET-scan performed. An ALC/AMC ratio ≥1.1 cut-off was used in the study based on our previous publication [Porrata et al, Hematologica 2012; 97(2): 262–9]. From 2000 until 2008, 111 classical HL patients qualified for the study. The cohort included 54% males and 46% females. The median age at diagnosis was 37 years (range: 18–83 years). The median follow-up was 2.8 years (range: 0.3–10.4 years). Patients with a negative interim PET-scan (N=98) presented with a higher ALC/AMC ratio at diagnosis (median of 2.32, range: 0.26–37.5) compared with patients with a positive interim PET-scan (N = 13) (median of 0.9, range: 0.29–3.10), p < 0.004. By univariate analysis, the ALC/AMC ratio at diagnosis and the interim PET-scan were predictors for PFS [ ALC/AMC ratio, R =0.13, 95% CI (0.05–0.35), p < 0.0002; and interim PET-scan, HR = 0.13, 95% CI (0.05–0.37), p < 0.0003] and TTP [ALC/AMC ratio, R =0.07, 95% CI (0.02–0.24), p < 0.0001; and interim PET-scan, HR = 0.05, 95% CI (0.01–0.18), p < 0.0003]. By multivariate analysis, ALC/AMC ratio at diagnosis and the interim PET-scan were independent predictors for PFS [ ALC/AMC ratio, R =0.13, 95% CI (0.07–0.63), p < 0.006; and interim PET-scan, HR = 0.11, 95%CI (0.02–0.47), p < 0.003] and TTP [ALC/AMC ratio, R =0.11, 95% CI (0.02–0.71), p < 0.02; and interim PET-scan, HR = 0.10, 95% CI (0.02–0.46), p < 0.003] when compared to the International Prognostic Score, limited versus advanced stage, and radiation. Patients were stratified into four groups: group 1 included patients with a negative interim PET-scan and ALC/AMC ratio at diagnosis ≥1.1 (N = 88); group 2 included positive interim PET-scan and ALC/AMC ratio at diagnosis ≥1.1 (N = 5); group 3 included negative PET-scan and ALC/AMC ratio at diagnosis < 1.1 (N = 10); and group 4 included positive PET-scan and ALC/AMC ratio at diagnosis <1.1 (N = 8). The three year PFS rates for each group were for goup1 95% (Events = 6); group 2 40% (Events = 3); group 3 56% (Events = 4); and group 4 50% (events = 4), p < 0.0001. The three year TTP rates for each group were: for group1 was 100% (Events = 0); for group 2 of 40% (Events = 3); for group 3 of 65% (Events = 3); and group 4 of 50% (events = 4), p < 0.0001. In conclusion, the ALC/AMC ratio at diagnosis is independent of the interim PET-scan to predict PFS and TTP in classical HL. Further studies are warranted to confirm our findings and to assess if the combination of the ALC/AMC ratio at diagnosis and interim PET can be use for planning of risk-adapted treatment. Disclosures: Ansell: Seattle Genetics, Inc.: Research Funding.

Abstract Background: CLL patients (pts) treated with novel targeted therapies continue to experience disease progression. Approximately 7-15% of relapsed CLL treated with ibrutinib or venetoclax developed Richter's syndrome (RS), an aggressive high grade lymphoma transformation. Standard chemotherapy has limited efficacy in RS. We hypothesized that checkpoint blockade would re-establish anti-tumor immune response in progressive CLL/RS and here we aim to update the clinical data and correlative analysis of MC1485: a phase 2 study of PD-1 blocking antibody pembrolizumab in relapsed/refractory CLL and RS. Methods: Relapsed/refractory CLL including RS enrolled in the CLL arm of MC1485 trial was reported here. The primary end point of this study is overall response rate (ORR). Pts with prior allogeneic stem cell transplant were excluded. Pembrolizumab 200 mg was administered intravenously every 3 weeks. NCI CTCAE v4.0 and IWCLL 2008 criteria were used for non-hematological adverse events (AE) and for CLL grade hematological AE. Tumor expression of PD-1 and PD-L1 were assessed with standard immunohistochemical (IHC) staining. Percentage expressions of individual antigens were analyzed with whole-slide scanning followed by image analysis with Image-Pro software (Media Cybernetics). Fluorescence in situ hybridization (FISH) was performed on available CLL/RS tissue sections to assess copy number of chromosome 9p region that contains PD-L1 and PD-L2. Results: 25 pts including 16 CLL and 9 RS (biopsy-proven large cell lymphoma) were enrolled in CLL arm. The median age was 69 years (46-81). Twelve (48%) pts had del(17p) or monosomy 17 or TP53 mutation. The median number of prior therapies was 4 (1-10). 96%, 72% or 48% of pts had received alkylator and anti-CD20 antibody, purine analog or anthracycline. Fifteen (60%) pts had prior ibrutinib and 12 (48%) progressed clinically while receiving ibrutinib, including 6 who progressed to RS and 6 who developed progressive CLL. The median number of pembrolizumab doses that pts received was 3 (1 to 21), administered over a median treatment duration of 11 weeks (1 to 56). Drug-related AE occurred in 21 pts (88%) with the most common ones being neutropenia in 9 (37%), cough in 7 (29%) and dyspnea in 6 (25%) pts. Drug-related grade 3 or above AE occurred in 9 (38%) pts with most common ones being thrombocytopenia (5, 21%), dyspnea (2, 8%), and fatigue (2, 8%). The most common immune-related AE was liver enzyme elevation (12%, 8% G3) and was reversible with therapy interruption or steroid therapy. Based on investigator assessment using the Revised Response Criteria for Lymphomas and IWCLL 2008 criteria, one RS pt had complete response (CR, 4%), 3 RS had partial responses (PR, 12%). Among 9 RS pts, 1 CR (11%), 3 PR (33%), 3 SD (33%) and 2 PD (22%) were observed. Thus the ORR in RS was 44%. No CLL pts achieved a CR/PR, 3 had SD and 9 had progressive disease (PD). The ORR of all pts was 16%. Of the 4 RS who had CR/PR, responses occurred early after 2 cycles of therapy and median duration of therapy for CR/PR pts was 8.3 months with data cut-off by June 30th 2016 (Figure 1A). The causes for therapy discontinuation in RS were PD (3, 33%), alternate therapy (2, 22%), and thrombocytopenia due to increased marrow CLL (1, 11%). Increased marrow CLL was observed in 2 RS pts with PR to RS phase of disease assessed by PET, thus the protocol was amended to allow addition of idelalisib/ibrutinib to control the underlying marrow CLL. For RS pts who had a CR/PR or SD, variable nodal responses were observed (Figure 1B). In particular, 6 RS who had prior ibrutinib experienced CR or PR or SD with nodal responses. After a median follow-up of 10.2 (1.9 to 16.1) months, the median overall survival (OS) for all pts was 10.7 months (95% confidence interval [CI], 5.4 to not reached). The 6 month OS rate for RS and CLL pts were 73% and 59%, respectively. Biomarker assessment using IHC analysis on 10 pts with available tumor/nodal tissues (6 RS and 4 CLL) showed an increased expression of PD-L1 (p = 0.02) and a trend for an increased expression of PD-1 (p = 0.1) in the group of pts with CR/ PR versus pts in the group with no clinical response. One out of 10 tested showed polysomic for chromosome 9p. Conclusion: Pembrolizumab had an acceptable safety profile in CLL and RS patients. We confirmed that pembrolizumab has substantial therapeutic activity in RS. Single-agent pembrolizumab does not appear to have clear activity in CLL. Disclosures Ding: Merck: Research Funding. Parikh:Pharmacyclics: Honoraria, Research Funding. Shanafelt:GlaxoSmithKline: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Hospira: Research Funding.

Abstract Abstract Our group recently reported a Phase III clinical trial (Porrata et al. Biology of Blood and Marrow Transplantation 2016; 22: 1017-1023) demonstrating that the infusion of the autograft-absolute lymphocyte count (A-ALC) and autograft natural killer cells (A-NKC) are survival prognostic factors in non-Hodgkin lymphoma (NHL) patients treated with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). A limitation of our Phase III clinical trial was the short-term follow-up of just two years. Therefore, we evaluated longer follow-up and assessed the role of the infused A-ALC, infused A-NKC, and peripheral blood absolute natural killer cell count (ANKC) recovery on survival post-APBHSCT. Of the 122 patients that participated in the Phase III trial, 111 patients were able to complete APBHSCT and included in the current study. With a median follow-up of 57.2 months (range: 2.1-84.6 months), superior overall survival (OS) and progression-free survival (PFS) was observed in patients infused with an A-ALC ≥ 0.5 x 109 lymphocytes/kg [OS: HR = 0.429, 95%CI, 0.128-0.828, p < 0.01; and PFS: HR = 0.456, 95% CI, 0.177-0.863, p < 0.01] and an A-NKC ≥ 0.09 x 109 cells/kg [OS: HR = 1.58e-3, 95% CI, 1.046e-6-0.179, p < 0.003; and PFS: HR= 1.58e-3, 95% CI, 7.81e-7-0.064, p < 0.003]. Furthermore, patients that maintained an ANKC ≥ 250 cells/µl at 3 months, 6 months, 9 months and 12 months post-APBHSCT also experienced superior OS (Figure 1A) and PFS (Figure 1B)[OS and PFS times in months were evaluated from infusion date of stem cells]. In the multivariate analysis a sustained ANKC ≥ 250 cells/µl was an independent predictor for OS (HR = 0.013, 95% CI, 0.001-0.063, p < 0.0001) and PFS (HR = 0.014, 95% CI, 0.001-0.067, p < 0.0001). This study is an extension of our Phase III clinical trial showing that sustained innate immunity by measuring the ANKC correlated with superior clinical outcomes; thus providing a platform to develop innate immunity immunotherapeutic strategists directing to improve clinical outcomes post-APBHSCT in NHL patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 1575 We recently demonstrated in a phase II study that the anti-CD22 monoclonal antibody epratuzumab added to RCHOP improved DLBCL survival parameters. Despite these advances, 30–40% of DLBCL patients still relapse and die of disease. Recent advances have led to the identification of a variety of intracellular oncogenic pathways as potential targets for lymphoma therapy. Specifically, many studies have found that activation of the Signal transducer and activator of transcription 3 (STAT3) pathway promotes tumor cell survival in various types of cancers. STAT3 is a transcription factor and exerts its anti-apoptototic effect through several downstream targets such as MYC. MYC protein can be expressed in lymphoma cells with or without the presence of MYC translocation. The frequency of phosphorylated STAT3 (pSTAT3) and MYC expression and their prognostic relevance are unknown within diffuse large B-cell lymphoma (DLBCL), germinal center B-cell (GCB) and non-GCB subtypes. This study studied the tumor cell expression of pSTAT3 and MYC by IHC paired with serum cytokine levels in a DLBCL patient population uniformly treated on N0489. DLBCL tumor samples (n=38) were stained for detection of nuclear pSTAT3 expression. Using a threshold of ≥30% of tumor nuclei staining positive, 35 % (14/40) of tumors were pSTAT3+. An additional 17% (7/40) had between 10–30% pSTAT3+ cells. Non-malignant tonsil tissues (n=10) were positive for tSTAT3 in all cases but all but one case were pSTAT3 negative. Twenty-four of the same DLBCL tumors used for pSTAT3 expression were stained for MYC and 50% (12/24) were MYC positive (all nuclear) as defined by the criteria of ≥30% of cells staining positive. In cases (n=23) where both MYC and pSTAT3 IHC were performed, a positive pSTAT3 was more likely to have MYC expression whereas a positive MYC stain did not inform pSTAT3. By using a break apart probe for the MYC gene, MYC translocations in the major breakpoint regions were found in 10% (3/29) of cases. When MYC FISH was correlated with MYC IHC in the 24 DLBCL cases that had both techniques performed, all 3 MYC translocation cases were GCB by IHC, two were strongly positive for MYC by IHC, and 1 was negative. Among the 21 MYC FISH negative cases, 10 were MYC positive by IHC. These data suggest that MYC expression in lymphoma is not only controlled by genetic events such as translocations but also by other signaling pathways such as STAT3. pSTAT3 expression was correlated with an elevated serum LDH (p=0.0007). Neither MYC or pSTAT3 tumor expression correlated with other clinical or pathological features. Survival analysis revealed a trend toward shorter EFS for DLBCL patients whose tumors expressed MYC protein by IHC (p=0.2) or had a MYC translocation (p=0.09) by FISH; pSTAT3 expression status did not predict EFS (p=0.9). Within the GCB group 10 cases were MYC negative (10/17; 59%) and 7 cases were MYC positive (7/17; 41%). Among the non-GCB group 83% (5/6) were MYC positive. These data clearly suggest a trend of higher MYC positivity in the non-GCB DLBCL group (p=0.07). MYC positive cases had a clear trend of inferior EFS in both GCB (p=0.2) and in non-GCB (p=0.5) groups. The distribution of pSTAT3 (n=38) expression was also evaluated in the GCB (n=26) and non-GCB (n=12) DLBCL. In the GCB group 27% (7/26) were pSTAT3 positive compared to 58% (7/12) in the non-GCB group. Thus, there was a clear trend toward higher pSTAT3 positivity in non-GCB DLBCL tumors (p=0.06); however, pSTAT3 status did not correlate with EFS in either GCB or non-GCB DLBCL patients. In the present study we correlated pretreatment serum cytokines levels of these patients with pSTAT3 and MYC tumor cell expression. Out of the 30 cytokines tested, the only pre-treatment cytokines that were significantly correlated with pSTAT3 expression were IL-10 (p=0.05), G-CSF (p=0.03) and TNFa (p=0.04); none were correlated with MYC expression. Overall, our data provide evidence that over-expression of pSTAT3 and MYC is common in DLBCL. These biomarkers have potential as prognostic factors in the case of MYC and as a tool for selecting therapy for pSTAT3. MYC may be especially useful to further identify an adverse group of DLBCL patients within the otherwise favorable GCB tumor group. The availability of JAK/STAT and STAT-specific inhibitors provides the rationale to incorporate pSTAT3 staining in tumors from patients who are participating in these trials to learn if this biomarker can predict response Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1525 Background: Nodular lymphocyte predominant Hodgkin Lymphoma (NLPHL) is a more indolent form of Hodgkin Lymphoma that is usually associated with favorable outcomes. However, a number of reports have shown a tendency of transformation to more aggressive types of lymphoma, typically diffuse large B-cell lymphoma (DLBCL). Long-term data on the incidence and outcomes of transformed NLPHL is lacking in the literature. The aim of this study was to evaluate incidence, risk factors and outcomes of DLBCL transformation in NLPHL in a cohort of patients followed at a single institution. Methods: The actively maintained Mayo Clinic Lymphoma Database includes all consenting consecutive patients with lymphoma seen at Mayo Clinic Rochester. This was used to retrospectively identify patients with NLPHL. The study was approved by the Institutional Review Board. Pathology was reviewed by a hematopathologist and all transformations were histologically confirmed by WHO criteria. The clinical characteristics, therapy and outcomes of patients with NLPHL and DLBCL transformation were analyzed. The chi-square test was used to compare variables. Risk of progression was calculated using a person-year approach. Survival and freedom from transformation were estimated and compared using the Kaplan Meier method and log rank tests, respectively. Results: Between 1970 and 2010, 222 consecutive adult patients with NLPHL were identified. The median follow-up was 20 years. Of these, 17 (7.7%) developed a transformation to DLBCL during the course of the disease (Figure 1). The median time to transformation was 35 (6–248) months. Of these 17 patients, 13 (76.5%) were male, 11 (64.7%) had stage I/II and 6 (35.3%) had stage III/IV NLPHL. Transformation was the first relapse in most patients (12 patients, 70.6%) while five patients (29.4%) developed one or more relapses of NLPHL before transformation. Prior therapies for NLPHL were as follows: radiation therapy in 5 (29.4%), chemotherapy in 5 (29.4%) and combined chemotherapy and radiation in 6 (35.3%) patients. The median age at transformation was 45 years (30–87). Most patients (10 patients, 58.8%) presented with signs (palpable lymph nodes) or “B” symptoms. Eight patients (47.1%) had stage III/IV disease at the time of transformation. The most commonly used regimens for treatment of DLBCL were R-CHOP or CHOP (9 patients, 52.9%). Platinum based therapy was administered in 4 (23.5%) patients. Five patients (29.4%) required more than one line of therapy, and autologous stem cell transplant was utilized in two (11.7%) patients. Based on the observed 17 transformations during 2304 patient-years of follow-up, the rate of transformation was 0.74 per 100 patient-years. The five-year overall survival (OS) of patients with transformed disease (calculated from time of transformation) was 76.4%. The most common cause of death was lymphoma (75%). Following treatment for transformation, 5 patients (29.4%) relapsed. The OS in transformed patients was independent of prior therapies, and transformation did not adversely affect overall survival in our cohort (median survival of in 129 months in transformed versus 120 in non-transformed patients, P=0.33). In a univariate analysis of prior therapies, use of radiation therapy was associated with a significant delay in time to transformation (P= 0.0035) (Table 1, figure 2). Conclusions: The risk of transformation in NLPHL is 0.74% per year in this large single institution case series of NLPHL, and appears to be lower than that observed in follicular and other types of low grade lymphoma. The outcomes of patients with transformation were significantly better than reported in other types of transformed lymphoma and did not adversely affect OS. Disclosures: No relevant conflicts of interest to declare.

Abstract AMD3100, Plerixafor (A)+G-CSF (G) have safely and effectively allowed aHSC mobilization in Phase I and II studies. This Phase III, multicenter, randomized, double-blind, placebo controlled study compared the safety and efficacy of A+G versus Placebo (P)+G to mobilize and transplant patients with NHL. Methods: Adult NHL patients requiring an aHSC transplant, in first or second CR or PR were eligible to participate. Patients received G (10μg/kg/day) subcutaneously (SQ) for 4 days. On the evening of Day 4, patients received either A (240μg/kg SQ) or P. Patients underwent apheresis on Day 5 after an AM dose of G and 10–11 hours after administration of study treatment. Patients continued to receive the evening dose of study treatment, followed by AM dose of G and apheresis for up to a total of 4 aphereses or until ≥5 x 106 CD34+cells/kg were collected. Only study cells were used for transplant. Patients who failed to mobilize ≥2 x 106 CD34+cells/kg could enter into a rescue arm of A+G, without unblinding of randomized treatment. The primary endpoint was the percentage of patients who achieved ≥5 x 106 CD34+cells/kg in 4 or less aphereses days. All patients will be followed for ≥12 months post-transplant. Results: 298 patients were enrolled and randomized. All patients have completed 100 days follow-up and are included in this intent-to-treat analysis. Baseline characteristics were similar between groups. The primary endpoint was met in 89/150 (59%) patients in the A+G group and 29/148 (20%) patients in the P+G group, p<0.0001. 130/150 (87%) patients in the A+G group and 70/148 (47%) patients in the P+G group collected ≥2 x 106 CD34+cells/kg in 4 or less aphereses days, p<0.0001. Kaplan-Meir Estimates of Time to Trget Collection of ≥ × 106 CD34 + cells/kg Kaplan-Meir Estimates of Time to Trget Collection of ≥ × 106 CD34 + cells/kg The figure shows that more patients in the A+G group reached target after 1 day of apheresis than patients in the P+G group after 4 days of apheresis. A+G rescue was successful in 33/52 rescue patients in the P+G group and 4/10 rescue patients in the A+G group. 135 patients (90%) in A+G group and 82 patients (55%) in P+G group underwent transplantation. Median time to engraftment was Day 10 for PMN and Day 20 for platelets in both groups. Through 100 days, grafts were durable in all but 2 A+G (133/135) patients and in all P+G (82) patients. A+G patients experienced a higher incidence of GI effects (mild to moderate) and injection site erythema than P+G patients. There were 2 drug related serious adverse events in the A+G group and 1 in the P+G group. Conclusions: In this study, the addition of AMD3100 to G-CSF is generally safe and well tolerated and is superior to G-CSF alone for aHSC mobilization in NHL patients. A+G patients were statistically significantly more likely to achieve target cell collection quicker and to achieve sufficient cells for successful transplant than P+G patients.

Abstract AMD3100, Plerixafor (A)+G-CSF (G) have effectively allowed aHSC mobilization in Phase I and II studies. This Phase III, multicenter, randomized, double-blind, placebo controlled study compares the safety and efficacy of A+G Vs. placebo (P)+G to mobilize and transplant patients with MM. Methods: Adult MM patients requiring an aHSC transplant, in first or second CR or PR were eligible to participate. Patients were declared for single or tandem transplant with the second transplant occurring within 6 months from the first. Patients received G (10μg/kg/day) subcutaneously (SQ) for 4 days; on the evening of Day 4 they received either A (240μg/kg SQ) or P. Patients underwent apheresis on Day 5 after an AM dose of G and 10–11 hours after administration of study treatment. Patients continued to receive the evening dose of study treatment followed by AM dose of G and apheresis for up to a total of 4 apheresis or until ≥6 x 106 CD34+ cells/kg were collected. Patients who failed to collect ≥2 x 106 CD34+ cells/kg were eligible for rescue therapy with A+G, without unblinding of randomized treatment. Only study cells were used for transplant. The primary endpoint was the percentage of patients who achieved ≥6 x 106 CD34+ cells/kg in 2 or less apheresis days. All patients will be followed for ≥12 months post-transplant. Results: 302 patients were enrolled and randomized into the study. All have completed 100 days follow-up and are included in this intent-to-treat analysis. Baseline characteristics were similar between groups. The primary endpoint was met in 106/128 (72%) patients in the A+G group and 53/154 (34%) patients in the P+G group, p<0.0001. The figure shows that 54% of A+G patients reached target after 1 day of apheresis but 56% P+G patients required up to 4 days of apheresis to reach target. 7 patients in the P+G group required rescue therapy and all collected ≥2 x 106 CD34+ cells/kg after A+G rescue. 142 patients (96%) in A+G group and 136 patients (88%) in the P+G group underwent transplant. Tandem transplants were performed in 32 and 28 patients in A+G and P+G groups, respectively. Median time to engraftment was Day 11 for PMN and Day 18 for platelets in both groups. Grafts were durable in all patients in both group at ≥100 days post-transplant. Patients in the A+G group experienced more GI effects and injection site erythema than patients in the P+G group. These adverse events were generally mild. There were no drug related serious adverse events in either group. Conclusions: In this study, the addition of AMD3100 to G-CSF is generally safe and well tolerated and is superior to G-CSF alone for aHSC mobilization in MM patients. A+G patients were statistically significantly more likely to achieve target earlier than P+G patients and had successful transplant. Figure Figure