Citations

Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

PURPOSEStandard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy.PATIENTS AND METHODSOne hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital.RESULTSMean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed.CONCLUSIONSubjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

e24082 Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is associated with significant short- and long-term sequelae that affect patients’ overall quality of life (QoL) and their physical and psychological well-being. Studies have shown improvement in patient QoL and physician satisfaction with palliative care involvement in the allo-HCT process. However, patient and physician perceptions regarding palliative care often impact timely referral. We conducted a prospective study to examine patient perceptions of palliative care both before and after palliative care consultation during evaluation for allo-HCT. Methods: This is a prospective, single-center study, of patients > 18 years of age, who were referred for a palliative care consultation as part of standard evaluation for allo-HCT. Patients were administered a pre- and post-visit internally derived questionnaire to assess their understanding and comfort level with palliative care. The primary objective of this study was to examine patient perceptions of palliative care consultation during evaluation for allo-HCT. Primary end point was the change in patient pre- and post- questionnaire responses. Secondary endpoint was the completion of advance care planning documentation pre- and post- consultation. Results: We enrolled 32 patients (male = 14) undergoing evaluation for allo-HCT with a primary diagnosis of AML (n = 8), NHL (n = 8), MDS (n = 7), ALL (n = 2), and other (n = 7). Following consultation with palliative care there was a statistically significant increase in patient understanding of the reason for the appointment, p = 0.0006. There was also a significant increase in patient’s knowledge of palliative care, with only 28% describing their knowledge as “good” or “excellent” prior to consultation and 79.3% after consultation, p < 0.0001. There was an observed positive, non-statistically significant, trend in patient comfort level with palliative medicine with only 20.7% (n = 6) describing their comfort as “high” or “very high” prior to consultation and 51.7% (n = 15) after consultation, p = 0.60. There was a higher rate of completion of advance care planning documentation following consultation with palliative medicine 56.3% vs 71.4%, p = 0.042. Conclusions: Palliative care consultation prior to allo-HCT increases a patient’s understanding of the role of palliative medicine as part of their allo-HCT and improves advance care planning. These findings need to be validated in a larger, multicenter, patient cohort.

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph+ and Ph- ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph+ (N=132, 36%) or Ph- ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x109/L, P<.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]

Abstract Venetoclax (Ven) combined with a hypomethylating agent (HMA) has now emerged as an effective treatment regimen for acute myeloid leukemia, in both de novo and relapsed/refractory setting. The current multicenter study retrospectively examined Ven + HMA treatment outcome among 32 patients (median age 69 years; 59% males) with blast‐phase myeloproliferative neoplasm (MPN‐BP). Pre‐leukemic phenotype included essential thrombocythemia (ET)/post‐ET myelofibrosis (34%), polycythemia vera (PV)/post‐PV myelofibrosis (38%) and primary myelofibrosis (28%). Twenty‐nine study patients were fully annotated cytogenetically and molecularly (NGS): 69% harbored complex karyotype and/or mutations, including TP53 (41%), IDH1/2 (21%), ASXL1 (21%), N/KRAS (14%), SRSF2 (10%), EZH2 (10%) and U2AF1 (7%). All patients received Ven combined with either azacitidine ( n = 12) or decitabine ( n = 20); either up front ( n = 23) or after failing another induction therapy ( n = 9). Complete remission with (CR) or without (CRi) count recovery was achieved in 14 (44%) patients and was more likely to occur in the absence of pre‐leukemic PV/post‐PV myelofibrosis phenotype ( p < .01), complex karyotype ( p < .01) or K/NRAS ( p = .03) mutations; seven of eight patients (88%) without vs four of 21 (19%) with complex karyotype or K/NRAS mutation achieved CR/CRi ( p < .01); all 11 informative patients with pre‐leukemic PV/post‐PV myelofibrosis phenotype displayed complex karyotype ( p < .01). In contrast, neither TP53 ( p = .45) nor IDH1/2 ( p = .63) mutations affected response. Compared to historical controls treated with HMA alone ( n = 26), the CR/CRi rate (44% vs 4%) and median survival (8 vs 5.5 months) were more favorable with Ven + HMA, but without significant difference in overall survival. Importantly, six patients with CR/CRi subsequently received allogeneic hematopoietic stem cell transplant (AHSCT). Note, Ven + HMA produces robust CR/CRi rates in MPN‐BP, especially in the absence of RAS mutations and complex karyotype, thus enabling AHSCT, in some patients.

Abstract BACKGROUND: Recurrent isocitrate dehydrogenase (IDH) 1 mutations are observed in 6-10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120), a potent, selective, oral, small-molecule inhibitor of the mutant IDH1 (mIDH1) protein, is a promising therapeutic candidate for the treatment of patients with mIDH1 AML. Through inhibition of mIDH1, ivosidenib suppresses the abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to clinical responses via differentiation of malignant cells. AIM: To report safety and efficacy data from the first-in-human phase 1 study of ivosidenib in patients with mIDH1 advanced hematologic malignancies including relapsed/refractory (R/R) AML (NCT02074839). This is the first report of data from the 4 expansion cohorts, with a total of 258 patients treated on study. METHODS: The ongoing phase 1 study assesses the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and clinical activity of ivosidenib in mIDH1 hematologic malignancies. Enrollment was completed on May 8, 2017. During dose escalation, patients received ivosidenib as a single agent orally once daily (QD) or twice daily (BID) in 28-day cycles. The MTD was not reached and 500 mg QD was selected as the recommended dose to be tested in 4 expansion cohorts: R/R AML (Arms 1 and 4, where Arm 1 patients are those with relapse after transplantation, second or later relapse, resistance to initial induction or reinduction treatment, or relapse within 1 year of initial treatment, and Arm 4 patients have R/R AML but are not eligible for Arm 1); untreated AML (Arm 2); and other advanced hematologic malignancies including myelodysplastic syndrome (MDS) (Arm 3). Updated safety data will be presented for all patients. Efficacy outcomes will be presented for all R/R AML patients treated at 500 mg QD across the dose escalation and expansion cohorts who received their first dose of ivosidenib at least 6 months prior to the analysis cut-off date of May 12, 2017, as well as for the poorest prognosis Arm 1 subset. Efficacy data for all treated patients from the other expansion cohorts (untreated AML and other advanced hematologic malignancies including MDS) will also be presented. RESULTS: In all, 258 patients (78 in dose escalation, 180 in expansion) were treated with ivosidenib. As of May 12, 2017, 62 of 258 (24%) patients were continuing on treatment. The median duration of exposure to ivosidenib was 3.5 months (range 0.1-33.5). Twenty-two (8.5%) patients discontinued treatment to proceed to allogeneic stem cell transplantation. Treatment was well tolerated; the most common adverse events (AEs) (n=258) of any grade irrespective of causality occurring in ≥20% of patients were diarrhea (33%), leukocytosis (30%), nausea (30%), fatigue (29%), febrile neutropenia (25%), dyspnea (24%), anemia (23%), QT prolongation (23%), peripheral edema (22%), pyrexia (21%), and decreased appetite (20%). The majority of these AEs were grades 1-2 and reported as unrelated to treatment. Differentiation syndrome (DS) was observed in 29 of 258 (11.2%) patients, including grade ≥3 DS in 14 (5.4%); study drug was held owing to DS in 11 patients (4.3%), and no instances of DS led to permanent treatment discontinuation or death. The primary efficacy endpoint for R/R AML is the CR+CRh rate, i.e., the rate of complete remission (CR according to modified IWG 2003 criteria plus CR with partial hematologic recovery, defined as CR except absolute neutrophil count &gt;0.5 × 109/L [500/µL] and platelet count &gt;50 × 109/L [50,000/µL]). Among 125 Arm 1 R/R AML patients receiving ivosidenib 500 mg QD across dose escalation and expansion who received their first dose at least 6 months prior to the analysis cutoff date, the CR+CRh rate was 30.4% (95% CI 22.5%, 39.3%), including CR in 27 (21.6%) and CRh in 11 (8.8%) patients. Median duration of CR+CRh was 8.2 months (95% CI 5.5, 12.0), and duration of CR was 9.3 months (95% CI 5.6, 18.3). The overall response rate (CR+CRi/CRp+PR+MLFS) was 41.6% (95% CI 32.9%, 50.8%) (52/125 patients). CONCLUSION: Ivosidenib monotherapy is well tolerated in patients with mIDH1 AML and other advanced hematologic malignancies. In a high-risk, molecularly defined R/R AML patient population with unmet medical need, ivosidenib induced durable remissions and improved patient outcomes. These findings support the role of ivosidenib as an effective, oral, targeted treatment for patients with mIDH1 AML. Disclosures DiNardo: Celgene: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. De Botton: Pfizer: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Servier: Honoraria; Agios: Honoraria, Research Funding. Stein: GSK: Other: Advisory Board, Research Funding; Constellation Pharma: Research Funding; Seattle Genetics: Research Funding; Agios Pharmaceuticals, Inc.: Consultancy, Research Funding; Celgene Corporation: Consultancy, Other: Travel expenses, Research Funding; Pfizer: Consultancy, Other: Travel expenses; Novartis: Consultancy, Research Funding. Roboz: AbbVie, Agios, Amgen, Amphivena, Array Biopharma Inc., Astex, AstraZeneca, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Novartis, Onconova, Pfizer, Roche Pharmace: Consultancy; Cellectis: Research Funding. Mims: Novartis: Honoraria. Pollyea: Takeda, Ariad, Alexion, Celgene, Pfizer, Pharmacyclics, Gilead, Jazz, Servier, Curis: Membership on an entity's Board of Directors or advisory committees; Agios, Pfizer: Research Funding. Altman: Syros: Consultancy; NCCN: Other: Educational speaker; BMS: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Ceplene: Consultancy; Janssen Pharmaceuticals: Consultancy; Novartis: Consultancy; ASH: Other: Educational speaker. Collins: Celgene Corporation: Research Funding; Agios: Research Funding; Arog: Research Funding; BMS: Research Funding. Mannis: Curis: Honoraria; Juno: Research Funding; Agios: Research Funding; Amgen: Honoraria. Uy: GlycoMimetics: Consultancy; Novartis: Consultancy, Other: Travel Suppport; Boehringer Ingelheim: Consultancy. Fathi: Juno: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Medimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stein: Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy. Erba: Celgene: Consultancy, Other: Chair, Scientific Steering Committee , Speakers Bureau; Incyte: all research support paid to University of Alabama, Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Other: all research support paid to University of Alabama, Research Funding; Daiichi Sankyo: Consultancy, Other: all research support paid to University of Alabama, Research Funding; ImmunoGen: Consultancy, Other: all research support paid to University of Alabama, Research Funding; MacroGen: Consultancy; Ono: Consultancy; Pfizer: Consultancy; Seattle Genetics: Consultancy, Other: all research support paid to University of Alabama, Research Funding; Sunesis: Consultancy; Millennium/Takeda: Consultancy, Other: all research support paid to University of Alabama, Research Funding; Agios: Other: all research support paid to University of Alabama, Research Funding; Juno: Other: all research support paid to University of Alabama, Research Funding; Astellas: Other: all research support paid to University of Alabama, Research Funding; Celator: Other: all research support paid to University of Alabama, Research Funding; Janssen: Other: all research support paid to University of Alabama, Research Funding; Glycomimetics: Other: Chair, Data and Safety Monitoring Committee. Traer: ImmunoGen: Consultancy; Tolero: Consultancy; Notable Labs: Equity Ownership. Stuart: Pharmacyclics LLC, an AbbVie Company: Research Funding; Amgen: Consultancy, Honoraria; Agios: Research Funding; Celator/Jazz: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel Support, Research Funding; Bayer: Research Funding; Novartis: Research Funding; Incyte: Research Funding; ONO: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; MedImmune: Research Funding; Cantex: Research Funding; Astellas: Research Funding. Arellano: Cephalon Oncology: Research Funding. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees. Yen: Agios: Employment, Equity Ownership. Kapsalis: Agios: Employment, Equity Ownership. Liu: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Goldwasser: Agios: Employment, Equity Ownership. Agresta: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Attar: Agios: Employment, Equity Ownership. Stone: Novartis: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Fuji Film: Consultancy; Jazz: Consultancy; Astellas: Consultancy; Pfizer: Consultancy; Arog: Consultancy; Ono: Consultancy; Agios: Consultancy; Sumitomo: Consultancy. Kantarjian: ARIAD: Research Funding; Bristol-Meyers Squibb: Research Funding; Delta-Fly Pharma: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Novartis: Research Funding.

AbstractIntroductionHypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi‐cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B‐cell lymphoma.MethodsWe conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi‐cel.ResultsThis analysis included 81 patients. Two patients had no available SA levels preceding axi‐cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1‐year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups.ConclusionNotwithstanding the limitations related to the relatively small sample size, axi‐cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.

Introduction: Patient-reported outcomes (PROs) such as quality of life (QOL) are variably affected in patients with myelodysplastic syndromes (MDS), but the heterogeneous composition of disease states grouped together as "MDS" increases the difficulty of assessing and understanding these outcomes. Moreover, little is known about the potential relationship between QOL and frailty in this population. Methods: The NHLBI MDS Natural History Study (NCT02775383) is a prospective cohort enrolling patients undergoing diagnostic work up for suspected MDS or MDS/myeloproliferative neoplasms (MPNs) in the setting of cytopenias. Untreated participants undergo bone marrow assessment with centralized histopathology review at enrollment for assignment into subcategories for longitudinal follow-up: MDS, MDS/MPN, ICUS, AML (&lt;30% blasts), and "At-Risk" (cases with sub-threshold dysplasia or select karyotypic or genetic mutations). PRO and frailty data are collected at enrollment and every six months thereafter. PRO instruments include MDS-specific (QUALMS) and general (FACT-G, PROMIS Fatigue Short Form 7a, EQ-5D-5L) instruments, and a measure of frailty (VES-13). While no frailty instrument alone has been shown to be a substitute for comprehensive geriatric assessment, VES-13 has been successfully used in cancer-related studies for basic screening, where a score of 3 or more is considered frail (vulnerable). An analysis of variance (ANOVA) was used for the overall comparisons of mean baseline scores between diagnostic categories. Pairwise comparisons of scores between diagnostic categories and vulnerability subgroups were performed via two-sample t-tests. Results : Of 835 participants assessed for eligibility, 369 (44%) were classified as MDS, MDS/MPN, AML, ICUS or At-Risk, and further evaluated. Mean age was 72 years (standard deviation (SD)=10.7) and 68% were male. Mean baseline scores on the PRO measures are compared between diagnostic categories in the Table; scores did not differ significantly across categories. In particular, no significant differences were found between MDS and the other diagnostic categories. ICUS had similar QOL scores to MDS and MDS/MPN (e.g., means (SD) on EQ-5D-5L of 74.1 (17.8) in ICUS and 70.8 (19.4) in MDS, p=0.348) but had significantly higher scores than those for AML on EQ-5D-5L (60.7 (28.4), p=0.031). For the 216 participants with diagnostically-confirmed MDS, QOL impairment was similar to that routinely seen in other cancers; for example, the mean total FACT-G was 81.8 (SD=15.9), similar to localized breast cancer (82.4, SD=16.2), localized colorectal cancer (79.6, SD=16.1), and lung cancer with no current evidence of disease (82.6, SD=15.5; comparison means from Pearlman, Cancer, 2014). For frail/vulnerable participants with MDS or MDS/MPN (N=87), the most common reasons for vulnerability were age ≥75 years (68%), overall rating of health as poor or fair (62%), and difficulty with prolonged physical activity (90%) such as walking a quarter mile (75%) or doing heavy housework (70%). A minority also were vulnerable due to requiring help with instrumental activities of daily living (iADLS) such as shopping (28%) or managing money (16%). Mean QOL scores were compared between vulnerability subgroups (Figure). Vulnerable participants pooled over all diagnostic categories had significantly worse PROs than non-vulnerable participants for all measures (p&lt;0.001). In particular, vulnerable MDS participants scored significantly worse on the QUALMS (mean 64.4, SD=13.4) vs. non-vulnerable MDS participants (mean 72.7, SD=13.3), p&lt;0.001. Conclusions: Participants in our cohort with histologically-confirmed MDS-even low-grade MDS-had similar impairments in PROs as those with other cancers. Among those with histologically-confirmed MDS, vulnerable participants had significantly worse QOL on many measures compared to non-vulnerable participants, suggesting that this domain of function be specifically assessed in clinic. Moreover, while a "gestalt" of frailty may be inferred by observing how patients present and move in the office, these data suggest that other contributing domains, such as difficulty with prolonged physical activity and iADLs, should be evaluated explicitly. Disclosures Foran: H3Biosciences: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Takeda: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Agios: Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Actinium: Research Funding; Aprea: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Trillium: Research Funding; Revolution Medicine: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding. Gore:Abbvie: Consultancy, Honoraria, Research Funding. Padron:Incyte: Research Funding; Kura: Research Funding; Novartis: Honoraria; BMS: Research Funding. Sekeres:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda/Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background: ENA is an oral, selective inhibitor of IDH2 approved for the treatment (Tx) of patients (pts) with relapsed/refractory IDH2 mutated (IDH2m) AML. Here we report the results of a Phase 2 expansion and Phase 1b of the Beat AML Master Trial Phase 2/1b sub-study to assess the efficacy of Tx of newly diagnosed (ND) IDH2m AML pts ≥ 60 years of age with ENA monotherapy (ENAm) and subsequent response-driven addition of AZA Tx. (ClinicalTrials.gov NCT03013998). Methods: The study initiated with a 3-outcome, 2-stage Phase 2 design, which enrolled patients on ENAm for up to 5 cycles. Pts without CR/CRi after 5 cycles of ENAm, or progression/intolerance prior to this time, were transferred to Phase 1b to receive ENA + AZA (Figure 1). Key eligibility included ND IDH2m AML pts with age ≥ 60 years and ECOG performance status 0-2. Pts received ENAm 100 mg/day in continuous 28-day cycles and ENA + AZA (75 mg/m2 days 1-7 every 28 days) for Phase 1b. Response was assessed using 2017 ELN AML criteria. The primary endpoint was CR/CRi rate. The 2-stage design required 24 pts and tested the null hypothesis (H0) that CR/CRi rate equaled 20% vs 50% and then expanded to test a revised H0 of 30% vs 50% in 60 pts (conditional alpha=0.025, power=77%). Expansion also allowed further assessment of safety of this treatment regimen. Results: At data cut off (06/18/2020), 60 pts enrolled, received ENAm, and were evaluable for the primary endpoint. Median age was 75 years and 52% were female (Table 1). Median time on ENAm was 4.7 months (mos). At data cut off, 12 pts were still on ENAm Tx. Most common reasons for discontinuing ENAm were Tx failure (defined as no response to treatment) (23 or 38%), disease progression (loss of response to treatment) (7 or 12%) and adverse events (AEs; 6 or 10%). Five pts (8%) went to transplant. CR/CRi was achieved in 28 pts (47%; adjusted 95% CI 28-59, unadjusted exact 95% CI 34-60) (Table 2). Responses were higher (p=0.04) among the 44 pts with IDH2 R140 (55%) as compared to the 16 with IDH2 R172 mutation (25%) further supporting distinct biology between these subsets. After a median follow up of 14.6 mos, the median overall survival (mOS) was 24.4 mos (95% CI 10.6-not reached). The median duration of response was not reached with 12 mos estimation of 57% (95% CI 34-75). Overall, 20 ENA-related serious adverse events (SAEs) occurred in 15 pts, the most common was differentiation syndrome (12 or 20%) and 1 had ENA-related SAE of tumor lysis syndrome (1.7%). One pt had ENA-related Grade 5 AE (renal failure/death). Most common AEs of any grade (in ≥20%) were nausea, anemia, and low potassium (Table 3). The 7-day/30-day/60-day deaths observed with ENAm were 2%/5%/11%, respectively. Phase 1b: Seventeen pts had inadequate response to ENAm and transferred to Phase 1b to receive ENA + AZA. Median time on Tx (including ENAm) was 6.2 mos and median time on Tx after pts started ENA + AZA was 2.1 mos (Table 2). Most common reasons for discontinuing ENA + AZA included Tx failure (5 or 29%), disease progression (2 or 12%), transplant, death and AEs (each 2 or 12%). CR/CRi was 41% (exact 95% CI 18-67). After a median follow up of 12.7 mos, the mOS from start of ENA + AZA combination Tx was 8.9 mos. Four ENA-related SAEs occurred in 3 pts on ENA + AZA Tx and the most common was differentiation syndrome (2 or 12.5%). One dose-limiting toxicity (Grade 3 nausea) related to both Txs was observed. Most common AEs (≥20%) of any grade were anemia, low albumin and vomiting (Table 3). One death occurred at day 13 of ENA + AZA. Conclusions: In newly diagnosed pts ≥60 years old with IDH2m AML, ENA had a low early death rate, high CR/CRi rate (47%, adjusted 95% CI 28-59), and yielded durable remissions. The most common unique toxicity with ENA was differentiation syndrome that occurred in 20% of patients. In pts who did not achieve CR/CRi with ENAm, a subset of patients achieved CR/CRi with addition of AZA. This combined approach of serial therapy with ENA monotherapy followed by AZA addition in pts with sub-optimal response resulted in a mOS exceeding 2 years for pts enrolled on study. Further focus on improving response among patients with IDH2 R172 mutations, identifying subsets of pts not responding to ENA monotherapy, and integrating new targeted agents into this treatment regimen are warranted. Figure 1 Disclosures Stein: Syndax: Consultancy, Research Funding; Celgene Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Biotheryx: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Borate:Genentech: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Research Funding; AbbVie: Other: Investigator in AbbVie-funded clinical trials; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Baer:Takeda: Other: Institutional research funding; AbbVie: Other: Institutional research funding; Astellas: Other: Institutional research funding; Forma: Other: Institutional research funding; Kite: Other: Institutional research funding; Oscotec: Other: Institutional research funding; Incyte: Other: Institutional research funding. Kovacsovics:Agios: Honoraria; Astella: Honoraria; Pfizer: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Jazz: Honoraria. Schiller:Astellas Pharma: Honoraria, Research Funding; Celator: Research Funding; Constellation: Research Funding; Abbvie: Research Funding; Actinium: Research Funding; Ariad: Research Funding; Stemline: Speakers Bureau; Cyclacel: Research Funding; Daiichi Sankyo: Research Funding; Deciphera: Research Funding; DeltaFly: Research Funding; Bristol-Myers Squibb: Current equity holder in publicly-traded company, Research Funding; Forma: Research Funding; FujiFilm: Research Funding; Gamida: Research Funding; Genentech-Roche: Research Funding; Geron: Research Funding; Jazz Pharmaceuticals: Research Funding; Karyopharm: Research Funding; Kite Pharma: Research Funding; Mateon: Research Funding; MedImmune: Research Funding; Onconova: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Regimmune: Research Funding; Samus: Research Funding; Sangamo: Research Funding; Tolero: Research Funding; Trovagene: Research Funding; Kaiser Permanente: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Agios: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; AstraZeneca: Consultancy; Incyte: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding; Ono Pharma: Consultancy; Celgene: Research Funding, Speakers Bureau; Sanofi: Speakers Bureau; Gilead: Speakers Bureau. Olin:Astellas: Other: Site PI; Genentech: Other: Site PI; Pfizer: Other: Site PI; Daiichi Sankyo: Other: Site PI; Genentech: Consultancy; Amgen: Consultancy. Foran:Trillium: Research Funding; Xencor: Research Funding; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Boehringer Ingelheim: Research Funding; Actinium: Research Funding; Aprea: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Takeda: Research Funding; Revolution Medicine: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees. Lin:Trovagene: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Prescient Therapeutics: Research Funding; Abbvie: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding; Incyte: Research Funding; Pfizer: Research Funding; Mateon Therapeutics: Research Funding; Ono Pharmaceutical: Research Funding; Jazz: Research Funding; Gilead Sciences: Research Funding; Genetech-Roche: Research Funding; Celyad: Research Funding; Celgene: Research Funding. Patel:DAVA Pharmaceuticals: Honoraria; Celgene: Consultancy, Speakers Bureau; Agios: Consultancy; France Foundation: Honoraria. Foster:Daiichi Sankyo: Consultancy; Bellicum Pharmaceuticals: Research Funding; Macrogenics: Consultancy, Research Funding. Druker:Leukemia & Lymphoma Society: Research Funding; Henry Stewart Talks: Patents & Royalties; Iterion Therapeutics (formerly Beta Cat Pharmaceuticals): Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; GRAIL: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Patient True Talks: Consultancy; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millipore (formerly Upstate Biotechnology): Patents & Royalties; MolecularMD (acquired by ICON): Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; McGraw Hill: Patents & Royalties; Merck & Co: Patents & Royalties; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dana-Farber Cancer Institute: Patents & Royalties; EnLiven: Consultancy, Research Funding; Aptose Therapeutics Inc. (formerly Lorus): Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; ARIAD: Research Funding; Blueprint Medicines: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Aileron Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Oregon Health & Science University: Patents & Royalties. Byrd:Acerta Pharma: Research Funding; Syndax: Research Funding; Vincera: Research Funding; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau; Novartis: Research Funding; Kartos Therapeutics: Research Funding; Trillium: Research Funding; Leukemia and Lymphoma Society: Other; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding. Levine:Loxo: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Imago: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Qiagen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Research Funding; Amgen: Honoraria; Astellas: Consultancy; Morphosys: Consultancy; Novartis: Consultancy; Isoplexis: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Lilly: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Gilead: Honoraria. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy; Novartis: Speakers Bureau. OffLabel Disclosure: Enasidenib is not approved for the treatment of newly diagnosed AML.

Background CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a "do not eat" signal to suppress macrophage phagocytosis. Overexpression of CD47 can allow tumor cells to escape immune surveillance. TTI-621 (SIRPαFc) is a fusion protein consisting of the CD47 binding domain of human SIRPα linked to the Fc region of human IgG1, designed to enhance phagocytosis and antitumor activity by blocking the CD47-SIRPα interaction between malignant cells and macrophages, and engaging Fcγ receptors. Here we report updates from the first-in-human study of TTI-621 (NCT02663518) in hematologic malignancies. Methods Study Part 1 tested increasing weekly intravenous doses of TTI-621 based on 3+3 escalation. The maximum tolerated dose was initially determined to be 0.2 mg/kg based on dose limiting toxicity (DLT) of thrombocytopenia [Grade (Gr) 4 of any duration]. Expanded testing followed in patients (pts) with hematologic malignancies, including leukemia, lymphoma, and multiple myeloma. In Part 2, most pts received 0.2 mg/kg. However, based on investigator discretion, a subset of pts received escalating doses up to 0.5 mg/kg. In Part 3, pts with T-cell lymphomas received stepwise dose escalations from 0.2 to 0.5 mg/kg over the first 5−8 weeks. In over 200 pts tested in Parts 1−3, thrombocytopenia did not increase with dose, typically recovered within 2−4 days, and was not associated with clinical sequelae. Part 4 was then undertaken to optimize TTI-621 dosing and is currently escalating doses in a 3+3 manner through pre-planned dose levels (0.5, 0.7, 1, and 1.4 mg/kg) in pts with cutaneous T-cell lymphoma (CTCL). The DLT criteria was modified to require Gr 4 thrombocytopenia lasting &gt;72 hours. Safety monitoring includes weekly clinical laboratories and assessments of adverse events (AEs) per CTCAE v 4.03. Blood samples are obtained for pharmacokinetics (PK) and for pharmacodynamic (PD) assessments of receptor occupancy (RO) on normal peripheral T cells. Disease assessments are performed per Olsen's criteria. Results In Parts 1−3 (n=214), the most common related AEs were infusion-related reaction (IRR, 43%; 3% Gr ≥3), thrombocytopenia (30%; 22% Gr ≥3), chills (21%; 0% Gr ≥3), and fatigue (15%; 1% Gr ≥3). Objective responses to single agent TTI-621 were achieved in 14/71 (20%) NHL pts including CTCL (n=42, 1 CR, 7 PRs), PTCL (n=22, 2 CRs, 2 PRs) and DLBCL (n=7, 1 CR, 1 PR). In Part 4, as of July 10, 2020, 15 pts (9M/6F, median age 67 years) have enrolled into 4 dose cohorts (0.5−1.4 mg/kg). CTCL subtypes include mycosis fungoides (MF, n=10) and Sézary syndrome (n=5) with advanced (≥IIB) disease in 9 (60%) pts who received a median of 3 (range 1−12) prior systemic therapies. Related AEs have occurred in 11 (73%) pts including IRR (n=10) and thrombocytopenia (n=3); Gr ≥3 AEs have occurred in 4 (27%) pts including thrombocytopenia (n=3), IRRs (n=2), and exfoliative dermatitis (n=1). Thrombocytopenia generally occurred on dosing days, recovered in 2-4 days, and has not worsened with increasing doses. IRRs typically occurred during initial infusions. The Gr 3 IRR events occurred in 2 pts in the 1 and 1.4 mg/kg cohorts; low Gr IRRs have occurred across doses in 8 pts. IRRs typically resolved without recurrence and low Gr events often resolved allowing for completion of infusions. For initial infusions, the Gr 3 IRRs prompted increasing infusion times from 1 hour up to 4 hours and discretional use of steroid pre-medication. The exfoliative dermatitis occurred Day 80 and led to treatment discontinuation in 1 pt with MF whose underlying disease confounded the etiology. PK results reveal dose dependent increases in exposure; PD studies indicate ~60% RO at end of infusion up to 1 mg/kg. Antitumor activity to date includes 1 PR and 1 skin CR in 6 evaluable pts in the 1 mg/kg cohort; 2 responding pts bridged to allogeneic transplantation. The mean % change in mSWAT scores were -0.4%, -27%, and -37% for 0.5, 0.7 and 1 mg/kg cohorts, respectively. 1.4 mg/kg cohort results will be presented at the meeting. Conclusions In Parts 1−3, TTI-621 doses of 0.05 to 0.5 mg/kg were well-tolerated and demonstrated single agent activity in multiple hematologic malignancies. Preliminary data from Part 4 dose optimization indicate that weekly infusions of TTI-621 up to 1.4 mg/kg are well-tolerated without dose limiting or cumulative thrombocytopenia. Antitumor activity was seen at 1 mg/kg; dose escalation is continuing at 2 mg/kg. Disclosures Horwitz: Janssen: Consultancy; Verastem: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; GlaxoSmithKline: Consultancy; ASTEX: Consultancy; Portola: Consultancy, Research Funding; C4 Therapeutics: Consultancy; Beigene: Consultancy; Myeloid Therapeutics: Consultancy; Vividion Therapeutics: Consultancy; Infinity/Verastem: Research Funding; Aileron: Consultancy, Research Funding; ADCT Therapeutics: Consultancy, Research Funding; Affirmed: Consultancy; Trillium: Consultancy, Research Funding; Corvus: Consultancy; Millenium/Takeda: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Innate Pharma: Consultancy; Forty Seven: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Kura Oncology: Consultancy; Miragen: Consultancy; Mundipharma: Consultancy. Foran:Agios: Honoraria, Research Funding; H3Biosciences: Research Funding; Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy. Sawas:Flatiron Health: Current Employment; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Affimed: Research Funding; Roche: Current equity holder in publicly-traded company. Feldman:AstraZeneca: Consultancy; Viracta: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Janssen: Speakers Bureau; Bayer: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Takeda: Honoraria, Other: Travel expenses; Celgene: Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding; Corvus: Research Funding; Rhizen: Research Funding; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Portola: Research Funding. Sokol:EUSA Pharma: Consultancy, Honoraria, Speakers Bureau; Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mei:Sanofi: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees. Flinn:Gilead Sciences: Consultancy, Research Funding; F. Hoffmann-La Roche: Research Funding; Roche: Consultancy, Research Funding; Vincera Pharma: Consultancy; Agios: Research Funding; Iksuda Therapeutics: Consultancy; Great Point Partners: Consultancy; Genentech, Inc.: Research Funding; Forty Seven: Research Funding; Forma Therapeutics: Research Funding; ArQule: Research Funding; Kite Pharma: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Trillium Therapeutics: Research Funding; Triphase Research & Development Corp.: Research Funding; Curio Science: Consultancy; Constellation Pharmaceuticals: Research Funding; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Nurix Therapeutics: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Portola Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Research Funding; Teva: Research Funding; Loxo: Research Funding; BeiGene: Consultancy, Research Funding; Calithera Biosciences: Research Funding; Johnson & Johnson: Other; Rhizen Pharmaceuticals: Research Funding; Yingli Pharmaceuticals ≠: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Karyopharm Therapeutics: Research Funding; AstraZeneca: Consultancy, Research Funding; Incyte: Research Funding; Takeda: Consultancy, Research Funding; IGM Biosciences: Research Funding; Infinity Pharmaceuticals: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding; Merck: Research Funding. Villa:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; AZ: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria; Nano String: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Sandoz Canada: Consultancy, Honoraria; Immunovaccine: Consultancy, Honoraria; Purdue Pharma: Consultancy, Honoraria. Percival:Pfizer: Research Funding; Trillium: Research Funding; Nohla Therapeutics: Research Funding; Biosight: Research Funding; Oscotec: Research Funding; Cardiff Oncology: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Glycomimetics: Research Funding. Jagadeesh:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Research Funding; Debiopharm Group: Research Funding. Savage:Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; Roche (institutional): Research Funding; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria; BeiGene: Other: Steering Committee. Akilov:Mallinckrodt: Consultancy; Medivir: Consultancy; Seattle Genetics, Inc.: Consultancy; Kyowa Hakko Kirin: Consultancy; Soligenix: Honoraria; Pfizer: Research Funding; Actelion: Consultancy, Research Funding; Trillium Therapeutics Inc.: Consultancy, Research Funding. Diefenbach:Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding; LAM Therapeutics: Research Funding; Incyte: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Denovo: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Kim:Kyowa-Kirin Pharma: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Medivir: Membership on an entity's Board of Directors or advisory committees; Horizon Pharma: Consultancy, Research Funding; Merck: Research Funding; miRagen: Research Funding; Trillium: Research Funding; Galderma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus: Research Funding; Elorac: Research Funding; Forty Seven Inc: Research Funding; Neumedicine: Consultancy, Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Solingenix: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Research Funding. Lin:Trillium Therapeutics Inc.: Current Employment. Catalano:Trillium Therapeutics Inc.: Current Employment. Petrova:Trillium Therapeutics Inc.: Current Employment. Uger:Trillium Therapeutics Inc.: Current Employment. Molloy:Trillium Therapeutics Inc.: Current Employment. Large:Trillium Therapeutics Inc.: Current Employment. Shou:Trillium Therapeutics Inc.: Current Employment. Ansell:Affimed: Research Funding; Bristol Myers Squibb: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; ADC Therapeutics: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding.