Abstract: Current CGVHD prognostic and staging systems are still undergoing development and have identified plt count; CGVHD types progressive(P), quiescent(Q), de novo(DN); KPS, and GI involvement as significant risk factors affecting outcome. A simple reproducible staging system such as used for AGVHD to apply in clinical trials is still lacking. We evaluated whether the PSE dose required to control CGVHD at 3 months from diagnosis would have a prognostic effect on survival and in and of itself serve as a criteria for secondary intervention or investigational therapy. We hypothesized that by 3 months from start of treatment patients would be on the lowest dose dictated by medical necessity rather than by physician driven dose preference. A retrospective analysis of charts from 109 patients diagnosed with CGVHD between 6/2000 and 6/2003 was done. Data collected included age, donor type(mud/sib), plt count, CGVHD type(P/Q/DN), KPS, GI involvement. Outcome analysis included survival and cause of death. PSE dose was calculated in mg/kg at 3 months from first diagnosis of CGVHD. With a median follow up of 47.2 months(range 6.6–67.2) relapse censored survival of patients on a 3 month PSE dose of more than .3 mg/kg was 53% compared to all lower doses 86%(P.03). In a univariate analysis only PSE dose (P .05) and KPS (P & lt;.01) were significant with plt count approaching significance (P .11). In a multivariate analysis again only PSE dose and KPS were significant (Table 1). Table Univariate Multivariate Variable Value N # of deaths Hazard Rate Ratio (95% CI) p value Hazard Rate Ratio (95% CI) p value Prednisone at 3 month 0 20 1 Baseline 0.05 Baseline 0.1–0.14 18 2 3.0 (0.3–32.7) 3.7 (0.3–43.4) 0.33 0.15–0.29 22 3 2.9 (0.3–28.2) 3.4 (0.3–34.5) 0.32 0.3–0.59 16 7 9.8 (1.2–79.4) 9.3 (1.1–76.0) 0.04 0.6–0.99 0 0 n/a n/a n/a ≥1.0 0 0 n/a n/a n/a cGVHD class Denovo 29 5 Baseline 0.54 Progressive 23 7 1.9 (0.6–6.0) Quiescent 57 13 1.3 (0.5–3.8) Donor type Sibling 48 9 Baseline 0.40 Unrelated 61 16 1.4 (0.6–3.2) Platelet count at 3 month & lt;100 28 9 Baseline 0.11 Baseline ≥100 81 16 0.5 (0.2–1.1) 0.7 (0.2–2.3) 0.59 KPS at 3 month & lt;80 14 7 Baseline & lt;0.01 Baseline ≥80 95 18 0.2 (0.1–0.5) 0.3 (0.0–1.3) 0.03 Lower GI at 3 month No 98 22 Baseline 0.78 Yes 9 2 1.2 (0.3–5.2) Overall survival by Prednisone dose Overall survival by Prednisone dose The analysis of this data to date suggests the PSE dose at 3 months may be an important independent clinical marker for subsequent CGVHD prognosis which could be used to decide which patients to include in 2nd line and experimental therapy trials.

Abstract: Introduction: This was a phase 1 dose escalation study (clinicaltrials.gov: NCT03150329) evaluating the addition of vorinostat to pembrolizumab in patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma, and follicular lymphoma. Here, we report the results in cHL. Methods: Adult patients with RR cHL who had received 1+ prior lines of therapy and were transplant ineligible received pembrolizumab and vorinostat in 21-day cycles. Prior anti-PD1 exposure was allowed. Patients were treated in a dose-escalation cohort with 2 dose levels (DL) using a Rolling 6 design and then on an expansion cohort at the recommended phase 2 dose (RP2D). Vorinostat 100mg BID (DL1) and 200 mg BID (DL2) were administered orally on days 1-5 and 8-12; all patients received pembrolizumab 200mg IV every 3 weeks. The primary endpoint was safety and determination of the RP2D. Responses were assessed by investigators using according to the 2014 Lugano Classification. Results: 32 cHL patients were enrolled, including 2 at DL1 and 30 at DL2 (RP2D). 78% had prior PD1 blockade and 56% were PD1-refractory. Gr 3+ AEs included hypertension (9%), neutropenia (9%), hypophosphatemia (9%), thrombocytopenia (6%), and lymphopenia (6%). Immune-related AEs included Gr 1-2 thyroiditis (13%), Gr 1 rash (6%) and Gr 3 esophagitis/duodenitis (3%). ORR was 72% and CR rate was 34%. Patients refractory to prior PD1 blockade (n=18) had ORR and CR rates of 56% and 11%, respectively. Conclusion: Pembrolizumab and vorinostat was well-tolerated with a high ORR rate in RR cHL including in anti-PD1-refractory disease.

Abstract: Background: In CTCL, intratumoral T cells are functionally exhausted and are characterized by the expression of immune inhibitory molecules such as PD1 and PD-L1 (Cancer Immunol Res 6; 2018). These findings justify the evaluation of immune checkpoint inhibition to reverse T cell exhaustion in CTCL. To this end, we initiated a phase 1/2 clinical trial of lenalidomide and durvalumab to determine the safety and efficacy of this regimen. Durvalumab is a human monoclonal antibody with high affinity and selectivity for PD-L1, with mechanisms of action that target the exhausted T cells and distinct cells within their environment. Lenalidomide, an oral immunomodulatory drug and analog of thalidomide, has previously shown activity in CTCL (Blood 123; 2014). Durvalumab may restore an anti-tumor immune response, and the combination of durvalumab and lenalidomide may enhance immune checkpoint blockade-induced immune responses. Methods: A Phase 1 portion is ongoing to characterize the safety and tolerability of durvalumab and lenalidomide combination. Patients (pts) are enrolled in sequential cohorts to receive durvalumab (fixed dose at 1500 mg) and dose escalation of lenalidomide (cohort 1 = 10 mg; cohort 2 = 15 mg; subsequent planned dose increments of 5 mg) to evaluate safety, efficacy and antitumor activity. Serial skin and blood samples were collected to assess the impact on the tumor micro-environment. We examined the correlation between clinical response and resistance and the following biological factors: PD1 clustering at the single molecule level using super-resolution microscopy, and expression of PD-L1 and ICOS at the tissue level by means of multiplex immunohistochemistry on pre-treatment primary cells (migrated from skin explants), and skin tissue (formalin-fixed and paraffin-embedded) from clinical trial subjects. Results: Six patients (5 males/1female, age 32-57 years) with refractory/advanced CTCL (mycosis fungoides/Sezary syndrome subtype), clinical stage IB (1), IIA (1), IIB (3), IIIA (1) have been enrolled as of July 2018. Duration time on treatment was 4 to 13+ months. Four patients showed improvement of skin disease with 2 patients achieved partial response with 〉 90% improvement of skin disease by mSWAT. Two patients developed progressive disease. No serious adverse events (AEs) were observed. The most frequently reported AEs were fatigue (n=6), skin pain (n=4), anemia (n=3) chills (n=4), and decreased appetite (n=3). All treatment-related AEs were Grade 1 or 2 in severity. One grade 3 fatigue occurred in one patient. No dose limiting toxicity has been observed to date. Using multispectral microscopy, we analyzed expression panels of several checkpoints: PD1, PD-L1, and ICOS on lesional skin biopsies at baseline. Strong PD-L1 and ICOS expression is observed from non-responders. Detectable levels of PD-L1, but low levels of ICOS is observed in responding patients. Quantitative super-resolution microscopy detected nanoscale clusters of PD1 in T cells from responders and no PD1 clustering was observed in T cells from non-responders. Conclusions: Durvalumab/lenalidomide has significant clinical activity in patients with refractory/advanced CTCL, which will be formally evaluated in the Phase 2 portion of this trial. Responses were durable and ongoing, and treatment was well tolerated with a low toxicity profile. Dose escalation is planned up to lenalidomide 20 mg daily. Our preliminary results from patients on trial demonstrated that immune signatures on skin biopsies at baseline may be predictive of response to checkpoint blockade and yield insights into mechanisms of therapeutic resistance. Disclosures Querfeld: Acelion: Membership on an entity's Board of Directors or advisory committees; Kyowa: Membership on an entity's Board of Directors or advisory committees; Bioniz: Membership on an entity's Board of Directors or advisory committees; Medivir: Membership on an entity's Board of Directors or advisory committees; Trillium Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Abstract: Background: Double-hit lymphomas (DHL) are a subset of diffuse large B-cell lymphoma (DLBCL) with concurrent chromosomal rearrangements involving the MYC and BCL2 or BCL6 genes, and are associated with dismal outcomes with standard upfront therapy. Double expressing lymphomas (DEL) are a subset of DLBCL with co-expression of MYC and BCL2 by immunohistochemistry (IHC), and also have a poor prognosis with standard therapy. While DHL status may be associated with inferior outcomes in patients with relapsed or refractory (rel/ref) disease (Cuccuini, Blood, 2012), little is known about the outcome of DHL patients with rel/ref disease who proceed to autologous stem cell transplantation (ASCT), and no study to date has examined the outcome of patients with DEL following ASCT. We evaluated the prognostic impact of DHL and DEL status in patients with rel/ref DLBCL who underwent ASCT at 2 centers. Methods: We retrospectively studied patients with rel/ref DLBCL, including transformed indolent lymphoma (TIL), who underwent ASCT at Brigham and Women's Hospital/Dana-Farber Cancer Institute (DFCI) and City of Hope (COH) between 1/2000 and 7/2013. The most recent biopsy prior to ASCT was used for testing when possible. IHC for MYC and BCL2 were performed using the Ventana (MYC: DFCI) and Leica BOND III (MYC: COH; BCL2: DFCI, COH) platforms according to standard protocols. For DEL, IHC cutoffs of ≥ 40% MYC-positive and ≥ 50% BCL2-positive cells were used (Johnson, JCO, 2012). Fluorescence in situ hybridization (FISH) for MYC was performed using LSI MYC dual-color break-apart probes (Abbott Molecular, Des Plaines, IL). MYC -rearranged cases had FISH for BCL2 and BCL6 performed using LSI BCL2 and BCL6 dual-color break-apart probes. DHL was defined as 〉 20% nuclei with break-apart signals for MYC and BCL-2 and/or BCL-6. Results: 201 patients with available archival tissue and clinical data were included. The median age was 60 (range 30-77) years; 60% were male; 26% had TIL; the median number of prior lines of therapy was 2 (range 2-5); 99% had prior rituximab; 53% had primary refractory disease or early ( 〈 6 mo) relapse; 60% were in CR by PET at ASCT; and conditioning regimens were: 66% CBV v 16% BEAM v 10% rituximab and/or ibritumomab tiuxetan-BEAM v 8% other. Overall, the 4y progression-free survival (PFS) and overall survival (OS) were 44% and 61%, respectively. Among 185 patients with complete IHC data, 38% were DEL. The 4y PFS and OS in patients with DEL compared to non-DEL patients were 37% v 52% (p =0.001), and 51% v 69% (p =0.005), respectively [Figure 1]. Results were similar using other reported IHC cutoffs for DEL (e.g. MYC ≥ 40%/BCL2 ≥ 70%, Green, JCO, 2012). Among 93 patients with complete FISH and IHC data available, 13% had MYC rearrangement: 4% were MYC/BCL2 DHL, 3% were MYC/BCL6 DHL, and 2% had rearrangements of all 3 loci. The 4y PFS and OS in DHL v non-DHL were 30% v 42% (p =0.042), and 40% v 57% (p =0.026), respectively. Patients with DEL (excluding DHL) and patients with DHL had similar PFS, which was inferior to non-DEL/non-DHL patients (4y PFS 35% v 30% v 45%, respectively, p =0.026) [Figure 2] . In multivariable models testing pre-ASCT variables, including PET response to salvage, DEL (HR 2.1, p=0.0002), TIL histology (HR 1.8, p=0.009), and SD/PD at ASCT (HR 2.9, p=0.025) were associated with poorer PFS, while DEL (HR 2.0, p=0.004) and SD/PD (HR 3.1, p=0.021) were associated with poorer OS. Neither MYC (≥ 40%) nor BCL2 (≥ 50%) expression alone was independently associated with PFS or OS. When analysis was restricted to the subset of patients with complete IHC and FISH data, DEL (HR 1.9, p=0.023), DHL (HR 2.4, p =0.048), and SD/PD at ASCT (HR 7.6, p =0.009) were associated with inferior PFS. No center effect was observed. Conclusions: DEL and DHL status are both associated with inferior PFS in patients with rel/ref DLBCL who undergo ASCT, regardless of remission status. Although ASCT remains a potentially curative approach, these patients should be targeted for study of pre- or post-ASCT relapse risk reduction strategies. Figure 1. (A) Overall survival and (B) Progression-Free Survival after ASCT in DEL vs non-DEL Patients Figure 1. (A) Overall survival and (B) Progression-Free Survival after ASCT in DEL vs non-DEL Patients Figure 2. Progression-Free Survival after ASCT in Patients with DEL vs DHL vs non-DEL/DHL Figure 2. Progression-Free Survival after ASCT in Patients with DEL vs DHL vs non-DEL/DHL Disclosures Herrera: Genentech: Research Funding; Pharmacyclics: Research Funding; Sequenta, Inc.: Research Funding. Budde:Atara Biotherapeutics: Consultancy; Seattle Genetics, Inc.: Research Funding; Merck: Research Funding; Ikara Inc: Patents & Royalties. Chen:Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau. Davids:Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Other: ad board. Nademanee:Seattle Genetics Inc.: Research Funding; Celgene: Consultancy; Gilead: Consultancy; Spectrum: Research Funding. Siddiqi:Pharmacyclics: Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Forman:Mustang: Research Funding; Amgen: Consultancy. Rodig:Perkin Elmer: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding. Krishnan:Onyx: Speakers Bureau; Janssen: Consultancy; Millenium: Speakers Bureau; BMS: Consultancy; Jazz: Consultancy; Celgene: Consultancy, Speakers Bureau. Armand:Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding; BMS: Research Funding; Sequenta, Inc.: Research Funding.

Abstract: Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume12 greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G2M and increased pre-GoDNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP] -thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.

Abstract: Hematopoietic stem cell transplant (HSCT) patients are at high risk for infection that can quickly progress to septic shock and multi-organ failure at various stages of their HSCT, with very high mortality and morbidity. One intervention that showed impact on outcomes is early goal directed therapy (EGDT), in which optimizing peripheral tissue oxygen delivery to meet hemodynamic endpoints using monitored early aggressive fluid resuscitation, hemoglobin correction, and pressors led to significant improvement in mortality and morbidity. Since that study did not include any HSCT patients who are considered such a high risk group with poor organ reserve function, immune suppression, micro-vascular injury caused by chemotherapy, radiation, implementing this aggressive approach for these patients in septic shock can raise concern of worsening respiratory, hemodynamic status and the added risk of inserting a new central line for monitoring central venous pressure (CVP) and Central venous Oxygen saturation (ScvO2) as a functional measure of cardiac output and oxygen delivery. In a pilot study we’ve tested the feasibility and safety of using EGDT approach in our HSCT patients in septic shock who needed ICU admission. We treated 10 consecutive patients upon admission to the ICU. Ages ranged from 24–70 years, all the patients were hypotensive with no response to at least 1500 mls of fluid boluses and low dose dopamine on the floor(5–7 mic/kg/min). Most of them were oliguric and some of them were in mild to moderate hypoxemia and tachypnea at the time of ICU transfer. In our institution most of these patients have right atrial catheters that can be used for measurement of CVP and ScvO2 through blood draws. In a sequenced approach CVP was kept between 8–12 mm hg with aggressive fluid resuscitation, Hgb at 10 and ScvO2 above 70%, levophed was used only if systolic BP was less than 90 mm hg. Dobutamine was used only if the ScvO2 was less than 70% despite all the above measures. All patients received 100 mg of hydrocortisone every 8 hours X 3–6 doses (to optimize adrenal function). All patients tolerated the treatment well. The average time of need for pressors was less than 14 hours. The average time with ICU care was 2.2 days. No complications reported as a result of the intervention, no end organ damage, and no renal or respiratory complications despite an average amount of IV fluid given in the 1st 12 hours of around 6.4 liters. All patients survived that ICU admission. The early aggressive approach of optimizing hemodynamic parameters in HSCT patients in septic shock is feasible, safe and may result in improved outcomes of survival, less ICU time and less end organ damage. Patients Characteristics Patient Diagnosis Bacteria Transplant state Time of ICU care Levophed time hours 12 hours fluid intake mls PS1 ALL P Aerogenosa pre-transplant 1 day 〈 12 8493 PS2 ALL none pre-transplant 2 days 〈 12 5079 HB3 AML Citribacter Freundii 5 months post allo 2 days 〈 17 8026 FD4 ALL E coli 8 years post allo 2 days 〈 12 5411 JS5 NHL Xanthomanas 65 days post allo 1 day none 4361 RN6 Multiple myeloma Serratia M Pre-transplant 2 days 〈 24 5007 AA7 AML E Coli Pre-transplant 2 days 〈 12 hours 5904 AT8 AML Klebsilla Pneumonia Pre-transplant 4 days 〈 12 hours 8000 DW9 Germ cell Tumor none Day 10 post auto 4 days 〈 12 hours 8307 FA10 AML Staph Aureus Day 67 post MUD 2 days 〈 24 hours 6130

Abstract: Tandem cycle high-dose melphalan (Mel) followed by Mel +/− total body radiation therapy improves progression-free (PFS) and overall survival (OS) in comparison to single cycle Mel, but is associated with 3% treatment-related mortality (TRM). We tested a new tandem regimen (THDCT) followed by maintenance therapy in order to lower TRM, while enhancing efficacy. Between 5/94 and 8/04, 114 patients (pts) were enrolled on 2 sequential studies. First, pts received Mel 150 mg/m2 [cycle 1 (C1)], oral busulfan (bu 16 mg/kg; 46 pts), and cyclophosphamide 120 mg/kg (Cy; C2); the next cohort received the same THDCT but bu was given intravenously (i.v. 12.8 mg/kg; 68 pts). All pts were to receive maintenance IF 3 million units/m2 given subcutaneously, 3 times/week. Pts participating on the 2nd study were to receive thal together with IF provided that they were not in CR at 6 months post-THDCT. Peripheral blood progenitor cell mobilization consisted of G-CSF 10 microgram/kg to procure 4 x 106 CD34+ cells/kg without (first 46 pts) or with Cy 1.5 g/m2 (last 68 pts). Pts ≤65 years, with responsive or stable MM, with 〈 40% marrow involvement, with a creatinine clearance of 70 cc/min and Karnofsky performance status of 70% were enrolled. Median age was 52 years (range: 29–65); 70% of pts were diagnosed with stage III MM, and 4 pts presented with plasma cell leukemia; 40% received prior radiation therapy. Pts received a median of 1(1–3) induction chemotherapy regimens; the median time from diagnosis to THDCT was 8 months (range: 2–73); 89% of pts received both C-s at a median of 76 days (range, 29–134). Among the first 46 pts (treated with oral bu) there were 7 cases of veno-occlusive disease (VOD): 3 were fatal, resulting in TRM of 7%. There were 8 cases of VOD in the 68 pt cohort treated with i.v. bu, one of whom died of multi-organ failure/sepsis (TRM:1.5%). Eighty nine percent of pts tolerated at least 1 million units/m2 of IF 2–3 times/week. Of pts receiving concomitant IF and thal (median dose of thal: 100 mg/day[range, 50–400]), only 7 pts tolerated both (median: 4 months; range: 1.6–18 months), 3 of whom converted to CR. At best response 44% pts were in CR and 12% achieved 90% reduction (very good partial remission (VGPR). For the entire group, 3-year PFS is 50% (95% CI, 40–59%) and OS is 71% (95%CI, 61–78%). Three-year PFS is 66% (95% CI 52–76%) vs. 29% (95% CI 16–42%) and OS is 87% (95% CI 76–93%) vs. 49% (95% CI 35–63%) favoring pts in CR and VGPR vs. all others. THDCT with Mel and i.v. bu /Cy and maintenance IF can be given safely, and may provide an alternative regimen to tandem Mel. Concomitant administration of IF and thal is not feasible. Thal should be used either in sequence or in lieu of IF as maintenance.

Abstract: Abstract 4151 Post-transplant lymphoproliferative disorder (PTLD) is a broad spectrum of lymphoproliferative disorders that can occur after solid organ transplant or hematopoietic stem cell transplant. The incidence ranges from 1% to 20% depending on the type of organ graft, the intensity of the immunosuppression and the Epstein-Barr virus (EBV) serostatus. It represents a serious and potentially life threatening complication, with reported mortality rate up to 40–50%. According to the World Health Organization classification system, PTLD are classified as early lesions (EL), polymorphic (p-PTLD), monomorphic (m-PTLD), and Hodgkin-like (HL). Here we analyzed the prognosis and clinical characteristics of 120 patients diagnosed and treated over a 19-year period (from 1990 to 2009). To the best of our knowledge, this is the largest series of PTLD to be reported by a single Institution. The cases were classified as follows: 70 (58.3%) m-PTLD, 34 (28.3%) p-PTLD, 14 (11.7%) EL, and 2 (1.7%) HL. In the m-PTLD group, 59 were of B-cell origin (52 DLBCL, 4 BL, 2 plasmacytoma-like, 1 multiple myeloma and 1 pleural effusion) and 10 were of T/NK cell lineage (4 peripheral T-cell lymphomas, 2 CTCL, 2 HSTCL, 1 T-ALL and 1 NK-cell lymphoma). The age of the patients ranged from 1 to 76 years, with 39 pediatric patients ( 〈 16 year old) and 81 adult patients. The EBV status of the PTLD, was determined in 94 cases, 58 (61.7%) were positive and 38 (38.3%) were negative, with no difference between pediatric and adult patients (p=0.11). CD 20 positivity was available in 106 specimens and was highly expressed in our series (87.6%) with no differences between adult and pediatric patients (p=0.4). Approximately half of the patients were diagnosed in stage I or II of disease (44.2%), and the other half in advanced stage III or IV (55.8%) with no substantial differences between adults and pediatrics (p=1). ECOG score 0 or 1 was observed in 2/3 of the patients (67.2%), and it was more frequently observed in pediatrics than in adults (respectively 80% and 61%) but the difference was not statistically significant (p=0.06). Younger age, CD 20 positivity, good ECOG score, platelet and absolute neutrophil count within normal limits correlated with a longer OS (p=0.001, P 〈 0.001, P 〈 0.001, P 〈 0.001 and p=0.003 respectively). PTLD subtype (i.e. EL, pPTLD, mPTLD, HL), gender, decade of diagnosis (1990-1999 vs 2000–2009), organ transplanted, EBV status, anemia, hypoalbuminemia, elevated LDH, extranodal sites involvement, grafted organ involvement, stage at diagnosis did not correlate with the OS in the univariate analysis. Using the recursive partitioning modeling, a new prognostic score was developed: ECOG score (0-1 vs 2–3), age (pediatrics [ 〈 16 year old], adults [ 〉 = 16 and 〈 60 year old] and elderly [ 〉 60 year old]) and CD 20 status (positive vs negative) provided a tree with 5 nodes (figure 1), separating the patients into 4 risk categories. The low-risk group included pediatric patients with ECOG score of 0–1 (median OS not reached); the intermediate-low-risk group included adults with an ECOG s core of 0–1 (median OS of 6.8 years); the intermediate-high-risk group included elderly with ECOG score 0–1 or pediatrics and adults with an ECOG score of 2–4 and CD20 positive or n/a (median OS of 1.8 years); the high-risk group included any patient with an ECOG score of 2–4 and CD20 negative, and elderly patients with CD20 positive or n/a (median OS of 1.3 months). In addition, in the group of adult patients with DLBCL PTLD and pPTLD (61 total), we analyzed the impact on OS of Rituximab treatment, as single agent or in combination with chemotherapy, compared to chemotherapy or immunosuppressant tapering alone. OS curves of patients treated with and without Rituximab adjusted by ECOG score, are shown in figure 2. The median OS of patients treated without rituximab with ECOG score 0–1 (18 patients) was 10.5 years, with ECOG 2–4 (13 patients) was 1.5 months compared to a median OS of 2.7 years in the rituximab group with ECOG score 0–1 (19 patients), and 1.2 years in the rituximab group with ECOG score 2–4 (11 patients) (p=0.8). This series proposed a new prognostic model for patients with PTLD, based on ECOG score, age and CD 20 expression. Interestingly, in our series, in a homogeneous population of adult patients with DLBCL and p-PTLD, the use of rituximab as single agent or in combination, compared to chemotherapy and immunosuppression tapering, did not show a survival benefit. Disclosures: O'Connor: Allos Therapeutics, Inc.: Research Funding.

Abstract: This phase 2 trial evaluated PET-adapted nivolumab alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240 mg nivolumab every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, whereas patients with progressive disease at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. Forty-three patients were evaluable for toxicity; 42 were evaluable for response. Thirty-four patients received nivolumab alone, and 9 patients received nivolumab+NICE. No unexpected toxicities were observed after nivolumab or NICE. After nivolumab, the overall response rate (ORR) was 81%, and the CR rate was 71%. Among 9 patients who received NICE, all responded, with 8 (89%) achieving CR. At the end of protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n = 43) were 72% and 95%, respectively. Among 33 patients who bridged directly to AHCT, the 2-year PFS was 94% (95% CI: 78-98). PET-adapted sequential salvage therapy with nivolumab/nivolumab+NICE was well tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This trial was registered at www.clinicaltrials.gov #NCT03016871.

Abstract: Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after ≥ 1 prior systemic therapy. The starting dose and schedule was 30 mg/m2/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m2/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m2/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m2/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.