ALBERT

Description: Background: Classical Hodgkin lymphoma (HL) has a unique histopathology, with rare malignant Hodgkin/Reed Sternberg (HRS) cells surrounded by a strong inflammatory cellular component in the tumor microenvironment (TME). Although extensive studies describe the interdependence of the HRS cells and the TME, the impact of HL on systemic immunity has not been well described. Here, we develop a new approach, employing a recently commercialized single cell cytokine secretion platform (IsoLight) to assess, precisely and comprehensively, the function of peripheral blood mononuclear cells (PBMCs) in HL patients. Methods: Cells were selected from 4 HL patients: 2 newly diagnosed who had a complete response (CR) to therapy standard first line therapy, and 2 relapsed patients who progressed on second line chemotherapy (PD). Cryopreserved PBMCs from a pre-treatment and post-treatment time point for each patient were thawed, rested overnight, stimulated with PMA/ionomycin and loaded into the IsoLight single cell cytokine secretion system. IsoLight captures single cells in microwells; as cytokines are secreted, they are bound by antibodies lining the microwell cover. Bound cytokines are then revealed by fluorescent secondary antibodies and photos are taken at various time points to assess fluorescence intensity, which corresponds to the relative amount of each cytokine secreted. Twenty thousand cells can be assayed per sample simultaneously. Results: The percentage of cytokine-secreting cells varied dramatically by donor (12%-48%), with monofunctional cells making only TNFa, MIP1b, or IL-15 dominating the functional landscape. Polyfunctional cells, capable of making three or more cytokines simultaneously represented only 0.1-7% of the cells in each sample, but there were more of these cells, and each secreted higher levels of cytokines, in individuals who responded to therapy with a CR. Responders also secreted higher levels of IL2, Perforin, IL4, IL12, MIP1a, and TNFb (p values ranging from 0.005 to 0.03), and lower levels of IL9 and IL22 (p=0.0028 and 0.021, respectively), compared to non-responders at diagnosis. Responders lost expression of IL4, IL7, and MIP1a over the course of treatment (pre- vs post-treatment, p=0.01 to 0.05), while non-responders gained cells that expressed IL4, IL5, IL10, IL17, and TNFb from diagnosis to end of treatment (p=0.001 to 0.05). Conclusion: This work represents an important methodological advance in immune monitoring for hematologic malignancies. Single cell cytokine secretion technology measures more cytokines simultaneously than flow cytometry, providing a sample-sparing and comprehensive overview of the functional landscape of immune cells in a patient. Moreover, the technology provides cell-by-cell information about cytokine secretion, unlike Luminex. Our work represents the first application of this technology to HL, which we use to define, for the first time, the particular combinations of 32 cytokines that can be secreted by individual immune cells. We also identify candidate cytokines whose frequency at diagnosis may predict treatment outcome, and reveal changes in cytokine levels over treatment time that may distinguish patients destined to relapse. Immunotherapy may impact PBMC function differently, this may partially explain the high efficacy of this therapy in the relapsed population. The impact of immunotherapy on cytokine levels is currently under investigation by our group in a larger study. Other important questions which are under investigation include the impact of prior chemotherapy on cytokine profiles in relapsed patients, and whether certain cytokines which increase during treatment may be a surrogage for tumor bulk in patients with PD. Cytokines elevated in patients with poor responses to treatment include IL9, IL10, IL17, and IL22, which may present attractive drug targets if validated in our larger ongoing follow-up study. Disclosures Diefenbach: Bristol-Myers Squibb: Consultancy, Research Funding; MEI: Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding. Hymes:Celgene: Consultancy. Martin:Janssen: Consultancy; Sandoz: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; I-MAB: Consultancy. Ruan:Celgene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie company: Research Funding; Juno: Consultancy; Kite: Consultancy. Leonard:Miltenyi: Consultancy; Akcea Therapeutics: Consultancy; Sandoz: Consultancy; AstraZeneca: Consultancy; Bayer Corporation: Consultancy; Epizyme, Inc: Consultancy; BeiGene: Consultancy; Miltenyi: Consultancy; ADC Therapeutics: Consultancy; Akcea Therapeutics: Consultancy; Sandoz: Consultancy; Celgene: Consultancy; Epizyme, Inc: Consultancy; Karyopharm Therapeutics: Consultancy; AstraZeneca: Consultancy; Bayer Corporation: Consultancy; Celgene: Consultancy; Sutro Biopharma: Consultancy; Merck: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; Gilead: Consultancy; Karyopharm Therapeutics: Consultancy; Sutro Biopharma: Consultancy; Nordic Nanovector: Consultancy; ADC Therapeutics: Consultancy; MorphoSys: Consultancy; Gilead: Consultancy; Nordic Nanovector: Consultancy; BeiGene: Consultancy; Merck: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; MorphoSys: Consultancy.

Description: Background: The CALGB 10603 RATIFY trial demonstrated that midostaurin, a multi-targeted small molecule FLT3 inhibitor, when given in combination with standard 3+7 induction consisting of daunorubicin 60mg/m2 for 3 doses and cytarabine 200mg/m2/day for 7 days significantly prolonged overall survival (OS) compared to placebo plus standard induction in FLT3 positive acute myeloid leukemia (AML) patients. The safety and efficacy of the other anthracycline commonly utilized in standard AML induction, idarubicin, has not been evaluated to date. Methods: A single-center retrospective review from May 2017 to July 2018 was performed. Patients were included if they had a diagnosis of FLT3 positive AML and received induction chemotherapy with idarubicin. The primary outcome was incidence of adverse effects attributed to midostaurin. Grading of adverse effects was in accordance with the Common Terminology and Criteria of Adverse Effects (CTCAE) version 5. Additional outcomes included OS, relapse-free survival (RFS), similar as in the Ratify trial, as well as detection of FLT3 on subsequent bone marrow biopsies. Results: Ten patients were included. All patients received induction therapy with idarubicin 12mg/m2 for 3 doses and cytarabine 100mg/m2/day for 7 days. Median age was 53 years (range: 33 to 66) and 6/10 were male. Eight of 10 patients exhibited internal tandem duplication (ITD) on diagnosis; two had FLT3 tyrosine kinase domain (TKD) D835. Eight patients had diploid cytogenetics; the other two patients had core-binding factor AML. Midostaurin was initiated on day 8 of induction in all but 2 patients, who started on day 11 and 12, respectively. Nine of ten patients completed all 28 planned doses of midostaurin. All patients received antifungal prophylaxis with micafungin throughout the course of midostaurin. The median time from day 1 of induction to neutrophil (〉500/µl) and platelet (〉100,000/µl) recovery was 23 days and 26 days, respectively. Granulocyte colony stimulating factor (G-CSF) was initiated for all patients after day 14 bone marrow biopsy, as per institutional procedure. Four of 10 patients experienced an adverse event attributed to midostaurin. Maculopapular rash was observed in 3 patients a median of 5 days after midostaurin initiation: 2 of 3 patients had a grade 2 rash and continued therapy with topical steroids; one patient had a grade 3 rash and discontinued midostaurin after 17 of 28 planned doses. A grade 1 drug fever was attributed to midostaurin in a fourth patient. Fevers persisted despite neutrophil recovery and subsequently dissipated after completion of the final midostaurin dose. Persistent FLT3 mutation was detected in 4/9 (1 not reported) day 14 bone marrow biopsies but was negative in 9/10 pts on day 28. The lone positive FLT3 result on day 28 occurred in a patient with refractory disease (〉5% blasts) necessitating salvage therapy. Notably, this patient only completed 17 of 28 planned doses. All other patients exhibited a complete response (CR) on day 28. The median follow-up time was 243 days (range: 57 to 394). Nine patients are alive at the time of reporting. Six patients proceeded to allogeneic transplantation -one death was attributed to transplant-related complications, occurring in the same patient needing salvage and reduced duration midostaurin. Two patients relapsed a median of 184 days after start of induction -both FLT3-ITD positive and neither having undergone allogeneic transplant prior to relapse. Conclusions: Midostaurin in combination with idarubicin-based induction 3+7 therapy in this first case series appears to be safe. While the incidence of rash was higher (30%) than reported in RATIFY, this only resulted in discontinuation of therapy in one patient. Although patient numbers are limited, 90% achieved a FLT3 negative CR after completion of induction therapy and six patients proceeded to allogeneic transplantation. A confounding variable includes the routine use of G-CSF, which likely contributed to the shorter duration from induction to neutrophil recovery observed compared to RATIFY (23 days vs 26 days). The influence of G-CSF use on outcome is uncertain, however represents an interesting observation. A randomized, prospective trial comparing midostaurin in combination with idarubicin versus daunorubicin at both 60mg/m2 and 90mg/m2 is warranted to establish the optimal anthracycline induction therapy for FLT3 mutated AML patients. Disclosures Al-Homsi: Celyad: Membership on an entity's Board of Directors or advisory committees. Diefenbach:Denovo: Research Funding; Merck: Consultancy, Research Funding; Acerta: Research Funding; Incyte: Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy; Seattle Genetics: Consultancy, Research Funding.

Description: Background: Over-expression of Aurora A has been shown in many subtypes of non-Hodgkin lymphoma (NHL) and is a negative prognostic factor in mantle cell lymphoma (MCL), where expression correlates with tumor proliferative signature (Ki67), and may contribute to cell cycle dysregulation. Aurora A regulates chromosomal stability through effects on mitosis and cell cycle regulation. Bortezomib increases both pro-apoptotic proteins and cell cycle dependent kinase inhibitors. Thus, there is a strong scientific rationale to combine Aurora A kinase and proteasome inhibition. We evaluated the combination of alistertib, an oral Aurora A kinase inhibitor, with bortezomib and rituximab in a CTEP sponsored phase 1 study of patients with relapsed /refractory (RR) low grade NHL or MCL. Methods: Patients with RR low grade NHL or MCL, who had received at least one line of immuno-chemotherapy were treated according to a 3 + 3 design with 3 dose escalation cohorts (DL1, DL2, and DL3) to identify the recommended phase 2 dose (RP2D) with an expansion cohort at the RPTD. Patients received alisertib 30mg BID (DL1 and DL2) or 40mg BID (DL3) on days 1-7, bortezomib subcutaneous 1mg/m2 (DL1) or 1.3 mg/m2 (DL2 and DL3) on days 1, 8, and 15, and rituximab 375mg/m2 on day 1 for the first 8 cycles, and subsequently q 3 months. An expansion cohort was treated at DL3. Treatment cycles were 28 days. Dose Limiting Toxicity (DLT) was defined within the first cycle of therapy. Results: A total of 24 patients at 3 sites were enrolled between 06/2013 and 02/2018, including DL1: 3, DL2: 7; DL3: 14. Median age was 64 (range 46-87). Twelve patients (50%) were male. Nineteen patients had low grade NHL, and 5 patients had MCL. Performance status was 0-1 in 22 (92%) patients, and 2 in 2 (8%) patients. Dose Escalation and Safety: The recommended phase II dose (RP2D) was DL3, with the only DLT in DL3 (prolonged grade 4 neutropenia). The most common grade 3-4 AEs at all dose levels were neutropenia (34%), thrombocytopenia (13%), anemia (8%), and fatigue (8%); grade 2 alopecia occurred in 37% (Table 1). Other grade 4 AEs included hypertension & hypotension, respiratory failure, hyperkalemia and hyperuricemia (n=1 (4%) each); one patient died of GI hemorrhage deemed unrelated to study treatment (NSAID overdose). Grade 3 neutropenia and leukopenia was seen in 4 patients and thrombocytopenia in 1. There was one grade 3 AE each of: hypertension, pulmonary hypertension, pneumonitis, fatigue, diarrhea, infusion reaction, lung infection, and febrile neutropenia. Efficacy: A total of 18 patients were evaluable for response. Five patients were not evaluable for response for the following reasons: withdrawal of consent (3, 1 each DL1, 2, 3), non-compliance (1 DL2), and death unrelated to study drug (1, DL2). For patients who were treated with at least 3 cycles of therapy, and had a restaging CT scan, the median duration of therapy was 142 days, (range 29-590). Response was seen in 7/18 evaluable patients for an overall response rate (ORR) of 38%; 4 of 18 patients (22%) had a complete response (CR), and 4 of 18 patients (22%) had a partial response (PR). An additional 8/18 patients (44%) had stable disease for a clinical benefit rate of 88%. With a median follow-up of 30.9 months, the median PFS was 6.9 months (95%CI 4.1-28.0) and median OS not reached. OS at 3 years was 64.9% (95% CI 44.1-95.3%; Fig. 1). Median duration of response was 14.1 mo (95% CI 2.63-NR). Conclusion: Alisertib in combination with bortezomib and rituximab is a well-tolerated regimen with significant and durable activity in heavily pretreated low grade NHL and MCL. The RP2D is DL3 (R + bortezomib 1.3mg/m2 and 1.8 alisertib 40mg bid). A correlation of Aurora Kinase tumor expression with clinical outcome is planned. Disclosures Barta: Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Diefenbach:Merck: Consultancy, Research Funding; Genentech: Consultancy; Incyte: Research Funding; Millenium/Takeda: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Acerta: Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Research Funding; Denovo: Research Funding.

Description: Background: In Hodgkin lymphoma (HL) the malignant Hodgkin Reed-Sternberg (HRS) cells comprise only a small fraction of the total cellular tumor population, which orchestrate an inflammatory microenvironment of reactive cells that propagate a permissive milieu for HL growth. This HRS cell mediated immune suppression has effects that extend beyond the direct tumor microenvironment. Previously we have shown that the circulating CD4 and CD8 T cells of relapsed (R) HL patients show high expression of the receptor programmed death-1 (PD-1), and that the central memory T cells (TCM) of both newly diagnosed (ND) and R HL patients are perturbed towards chronic activation. Here we describe immune activation and perturbation in the myeloid compartment of 20 HL patients with newly diagnosed (ND) or relapsed (R) disease. Methods: Informed consent obtained from patients with ND (n= 14) or R (n=6) HL treated since January of 2013. Blood samples were drawn pre-treatment, and at sequential time-points during and after therapy. Cryopreserved PBMCs were thawed then evaluated with multi-color flow cytometry. Cells were stained with fixable viability dye (eBioscience); then stained with fluorescent-conjugated antibodies. For intracellular staining, cells were fixed and permeabilized using FOXP3 staining kit (eBioscience) then stained with intracellular antibodies. Stained cells were analyzed using LSRII flow cytometer (BD Bioscience) and FlowJo software (Tree Star). The following anti-human antibodies were used to analyze myeloid subsets: CD3, CD19, CD16, HLA-DR, CD14, CD303, CD141. Monocytes are defined as CD14+HLA-DR+CD3-CD19-, plasmacytoid dendritic cells (pDCs) as: CD303+HLA-DR+CD14-CD3-CD19-CD16-, and dendritic cells (DCs) as: HLA-DR+CD141+CD14-CD303-CD3-CD19-CD16-(Biolegend). Singlet cells were gated based on forward and side scatter properties. Dead cells were excluded based on viability dye. Patient samples were compared to normal controls matched for age and sex (n=20). Results: The median HL patient age was 38 (range: 20-90 years). Twelveof the HL subjects were male and 8 were female. All but 1 of the ND HL patients were treated with upfront ABVD +/- consolidative radiation. Two out of 6 R patients had prior allogeneic stem cell transplant (alloSCT); they were not on immunosuppression. Thirteen patients (12 ND, 1 R) responded to therapy (11 CR and 2 PR); 4 patients (1 ND, 3 R) progressed on therapy or had stable disease, 2 patients do not have disease status confirmed. We observed a decrease in the proportion of systemic circulating plasmacytoid dendritic cells (pDCs), but not monocytes or DCs, in HL patients at baseline compared to healthy controls (Figure 1). Interestingly, the ratio of both DCs and pDCs to monocytes were greatly disturbed in HL patients compared to healthy subjects (Figure 2). After a single cycle of chemotherapy we noted an increase in pDCs, and a decrease in the ratio of monocytes to both DCs and pDCs and of DCs to pDCs in treated patients. Together these findings suggest a systemic imbalance within the monocyte-DC-pDC axis in HL patients compared to normal healthy controls, which appears to normalize after one cycle of treatment with chemotherapy. Conclusion: HL patients have evidence of perturbation in the systemic myeloid compartment, suggesting that the impact of HRS cells on their microenvironment may have systemic as well as local effects that extend to the myeloid compartment and to antigen presentation, as well as to T cell phenotypes. This underscores the rationale for understanding the role of systemic immune dysfunction in HL, and for the use of immune targeted therapies in HL. Correlation with clinical data, and functional studies to further characterize this immune dysregulation are ongoing. Disclosures Diefenbach: Merck: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Gillead: Equity Ownership; Seattle Genetics: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding. Martin:Gilead: Consultancy, Other: travel, accommodations, expenses; Janssen: Consultancy, Honoraria, Other: travel, accommodations, expenses; Celgene: Consultancy, Honoraria; Novartis: Consultancy; Teva: Research Funding; Acerta: Consultancy. Ruan:Seattle Genetics: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics, LLC, an AbbVie Company: Research Funding, Speakers Bureau; Janssen: Research Funding.

Description: Zanolimumab (previously referred to as HuMax-CD4) is a fully human monoclonal IgG1k antibody, targeting the CD4 molecule on T-cells. It exhibits cytotoxic and anti-proliferative effects and has previously shown efficacy in cutaneous T-cell lymphoma. We report the early safety and peripheral CD4+ cell depletion results from the open-label, dose escalation part of a US phase III efficacy study. So far, 21 patients have been recruited and the results from the 4 mg/kg dose group (9 patients) and 8 mg/kg dose group (6 patients) are available. Zanolimumab was administered iv, once weekly for 12 weeks. In total, 2 Serious Adverse Events have been reported. Of these, 1 case of large cell transformation in a patient with large cells present prior to inclusion was judged possibly related to treatment by investigator. No increase in toxicity was seen upon dose escalation. Marked depletion of CD4+ T-cells was observed after just 1 infusion of zanolimumab at both dose levels. One week following the last dose, the median (range) peripheral blood CD4+ T-cell count compared to baseline values was decreased from 831 per μL (167–1928) to 24 per μL (4–141) in 4 mg/kg dose-group and from 638 per μL (182–1024) to 9 per μL (4–19) in the 8 mg/kg dose-group. These initial data indicate that zanolimumab has an acceptable tolerability profile at the doses tested and results in a rapid and pronounced decrease in peripheral CD4+ counts in MF CTCL patients.

Description: It has been proposed that bacteria play a direct role in progression of cutaneous T cell lymphoma (CTCL), although definitive evidence is missing, and the underlying mechanism of how microbes contribute to disease progression remains unknown. The skin of CTCL patients is frequently colonized with Staphylococcus aureus (S. aureus) strains and infections with hospital and community associated strains of S. aureus are a frequent cause of morbidity and mortality among patients with advanced CTCL. Here we provide a comprehensive analysis of the association between CTCL and S. aureus colonization, and use our unique pre-clinical animal model of CTCL to determine the cause-effect relationship between skin-associated S. aureus and CTCL progression. To understand the relationship between bacterial colonization and CTCL we collected skin swabs from active lesions, unaffected skin and nares of CTCL patients to perform S. aureus cultures and 16S rRNA gene sequencing. Skin swabs of psoriasis patients and healthy donors served as controls. The frequency of S. aureus colonization determined by culture based techniques revealed that 〉65% of advanced stage patients had S. aureus present at lesional/tumor sites, while corresponding sites in patients with psoriasis and in healthy controls rarely had detectable S. aureus. Colonization rates correlated positively with the disease stage. Unbiased, 16s sequencing based analysis of the skin microbiome from advanced CTCL patients revealed that the overall skin microbiome of these patients is distinct from that of healthy individuals and patients with psoriasis. A lower phylogenetic diversity and significantly higher relative abundance of Staphylococcus species was found in CTCL patients. To determine the causal relationship between skin flora and progression of CTCL we used our mouse model of CTCL and assessed disease progression in both conventionally housed specific-pathogen-free (SPF) conditions and in germ free (GF) isolators using a standardized clinical score. The CD4CreSTAT3stopfl/+ mice express a hyper-active STAT3C mutant protein selectively in T lymphocytes and virtually all mutant mice develop T cell infiltration in the epidermis causing skin lesions resembling CTCL, by eight months of age. In contrast to the SPF housed animals, GF mice remained disease free or developed only a mild phenotype (clinical score 1 out of 5) after 11 months of follow-up. Notably, when GF CD4CreSTAT3stopfl/+ mice were transitioned to SPF conditions they all developed advanced disease. Finally, we examined the role of T cell antigen receptor (TCR) signaling in mediating the transformation of T lymphocytes. R26STAT3Cstopfl/+CD4Cre Rag2KO OTII mice express only OVA-specific TCRs. T cells from R26STAT3Cstopfl/+ CD4Cre Stim1fl/fl mice express a normal TCR repertoire, but exhibit defective T cell receptor signaling due to compromised calcium influx. Both strains failed to develop typical skin lesions, suggesting an essential role for TCR interaction with tumor microenvironment and microbial antigens in the pathogenesis of CTCL. In conclusion, we demonstrate a strong correlation between CTCL staging and rates of S. aureus colonization. Our study supports a cause-effect relationship between skin flora and CTCL oncogenesis. We propose that CTCL represents an antigen driven malignancy. Further studies using mono-colonization with single bacterial strains are needed to further interrogate the role of specific bacteria. Disclosures Hymes: Celgene: Consultancy. Odum:Micreos human Health B.V: Consultancy. Geskin:Merck: Other: Supported/Contracted Research; UpToDate: Patents & Royalties: Royalty, Receipt of Intellectual Property Rights / Patent Holder; Mallinckrodt: Consultancy, Honoraria, Other: Supported/Contracted Research; Helsinn: Consultancy, Honoraria, Other: Supported/Contracted Research; Stratpharma: Other: Supported/Contracted Research; Medivir: Consultancy, Honoraria; Medscape: Speakers Bureau; Actelion: Other: Supported/Contracted Research.

Description: Abstract 920 Background: Belinostat is a pan-HDAC inhibitor of the hydroxamate chemical class that is well-tolerated and has shown clinical activity. Methods: Open label, multicenter trial enrolling patients (pts) with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥ 1 prior systemic therapy. Pts received 1000 mg/m2 IV belinostat over 30 min on days 1 to 5 of a 3-wk cycle. Primary endpoint was objective response (OR) assessed by IWG criteria for PTCL and by SWAT (cutaneous lesions) and IWG criteria (non-cutaneous lesions) for CTCL. Pruritus in pts with CTCL was assessed using a 10-point scale; relief defined as reduction of pruritus score of ≥ 3 points in pts with baseline score ≥ 3. ECGs were monitored and reviewed centrally (pre-/ post-infusion ECGs on all treatment days in cycle 1, and pre-/ post-infusion ECGs on day 1 of subsequent cycles) to evaluate potential cardiac toxicity. Results: The study enrolled a total of 53 treated pts, including 20 and 29 evaluable pts with a diagnosis of PTCL and CTCL, respectively. The 20 pts with PTCL [10 PTCL-unspecified (PTCL-U), 3 anaplastic large cell lymphoma (ALCL), 3 angioimmunoblastic TCL (AITL), 3 NK/T-cell lymphoma, and 1 subcutaneous panniculitis-like TCL (SPTCL)] had received a median of 3 prior systemic therapies (range 1 – 10), and 40 % of them had stage IV disease. 5/20 (25%) PTCL pts responded with 2 CR (both in patients with PTCL-U) and 3 PR (PTCL-U, AITL, ALCL). The 5 responding pts had a median duration of response of 159+ days (range 1 – 504+). Additionally, SD was observed in 5 pts (2 PTCL-U, 2 NK/T-cell, and 1 ALCL) with median duration of SD of 109+ days (range 80 -185+). The 29 pts with CTCL [15 mycosis fungoides (MF), 7 Sezary syndrome (SS), 5 non MF/SS, 2 unclassified] had received a median of 1 prior skin directed therapies (range 0 – 4) and 3 prior systemic therapies (range 1 – 9), and 55 % of them had stage IV disease. 4/29 (14%) CTCL pts responded with 2 CR (ALCL, MF) and 2 PR (MF, SS). The 4 responding pts had a median duration of response of 273 days (range 48 - 469+). Importantly, time to response was short with a median of 16 days (range 14-35). In addition, SD was observed in 17 pts (10 MF, 3 SS, 2 non MF/SS, 2 unclassified) with current duration of up to 127 days. Pruritus relief (score reduction ≥ 3) was seen in 7 of 14 pts with significant baseline pruritis. Median time to pruritus relief was also short, 16 days (range 7-45). Hematological toxicity was minimal without any grade 4 events (shift from baseline) and only one pt each experiencing grade 3 neutropenia and grade 3 thrombocytopenia, respectively. No grade 3 QTcF prolongation was detected in more than 700 ECGs. Four grade 3/4 drug-related AEs were reported: pruritis, rash/erythema, edema, and adynamic ileus. Conclusions: Belinostat monotherapy is safe, well tolerated, and efficacious in pts with recurrent/refractory T-cell lymphoma with durable remissions in both CTCL and PTCL. These results are the basis for a pivotal study with belinostat monotherapy in pts with PTCL. Disclosures: Advani: Seattle Genetics, Inc.: Research Funding. Duvic:Topotarget: research support for conduct of clinical trial. Fagerberg:TopoTarget A/S: Employment, Equity Ownership. Foss:Eisai : Speakers Bureau.

Description: Alternative medicine has become more common as patients seek approaches to diseases where traditional medicine has failed. Treatment with ozone has been purported to have benefits for a variety of infectious, inflammatory and neoplastic conditions. Treatment can be administered by the intra arterial, intravenous, intra rectal and subcutaneous routes as well as ozonated autohaemotherapy. We describe a 44 year old woman who received treatment at an alternative medical center for recurrent breast cancer including laetrile, perflurocarbon emulsion, high dose ascorbic acid, vitamin K and extracorporeal treatment of her blood with ozone and ultraviolet light. After receiving her second treatment, she presented to our hospital with a syncopal episode and was found to be anemic (Hb 4 gm/dl). The LDH was 8X〉 ULN, the serum haptoglobin was undetectable, and the reticulocyte count was increased. The peripheral blood smear showed aniscocytosis, poikilocytosis and polychromasia. There was also severe acanthocytosis. Heinz bodies were not detected. The patient refused blood products and after 48h of hospitalization, her Hb rose to 7gm and she was discharged. She did not return for follow-up evaluation. Acanthocytosis has been associated with impairment of cholesterol membrane fluidity seen with acquired hepatic disease as well as some congenital diseases. Oxidative stress can lead to peroxidation of membrane phospholipids, and if the intrinsic repair mechanism of the RBC is overwhelmed, the RBCs transform into acanthocytes. To date, there has been no literature describing hemolysis associated with any of the individual treatments which this patient received; however the combination of treatments exposed the RBC’s to multiple oxidative stresses which might lead to lipid peroxidation and formation of acanthocytes. This case illustrates the potential problems that face clinicians when encountering patients who seek alternative therapy.