ALBERT

Description: Introduction: T cell exhaustion is a hallmark of CTCL and alterations in mRNA profiles correlate with immune checkpoint expression, with potential clinical relevance (Querfeld et al. 2018). There is no immunophenotypic marker that can distinguish malignant CD4+ T cells from benign CD4+ T cells in the infiltrate and intratumoral heterogeneity poses a major challenge to treatments and long-term remissions. The microenvironment in CTCL harbors multiple immune cells that may contribute to the development of resistance to drug treatments; however, the genomic and molecular determinants of response to therapeutic agents remain incompletely understood. The aim of our study was to distinguish malignant from non-malignant T cells based on TCR α/β repertoires and to understand the transcriptional landscapes of malignant and non-malignant cells in the TME while on anti-PD-L1 therapy. Methods: Migrated cells from skin explants were harvested and subsequently analyzed by our paired single-cell RNA and T cell receptor (TCR; alpha/beta) sequencing on ~3000-4000 cells from skin lesions of 6 patients with mycosis fungoides at baseline and cycle 1 day 15 with anti-PD-L1 + lenalidomide. Results: We identified 14 gene clusters. Differential expression (DE) of genes in each of the unique clusters were identified by comparing gene expression from cells in each cluster to that of all other cells in the dataset, using a cut-off of P 〈 0.05 and further requiring expression of the gene in 〉25% of cells in the cluster. Thus, DE-identified genes are expressed either uniquely or by a large proportion of cells within each cluster compared to all other clusters. TCR clones in these cells were also characterized. Through this combined analysis, we demonstrated differences in the diversity, clonal expansion and T cell phenotypes that differentiated expanded malignant T cell populations (cluster 0-3) from non-malignant T cells including tumor infiltrating lymphocytes (TILs), regulatory T cells (Tregs), NK/T cells, and from immune cells such as B cells, antigen presenting cells (dendritic cells, macrophages) and other cells (stromal, epithelial cells) (cluster 4-13). Comparing baseline to C1D15 we were able to identify microenvironmental changes that occurred during treatment, specifically characterized the expression and significance of PD1, LAG3, CTLA4, TIM3 and ICOS in malignant and non-malignant T cell clusters, which demonstrated differential expression of these targets in malignant T cells (clusters 0-4). Non-malignant T cell phenotyping revealed an enriched tumor-infiltrating CD8+ T cell population at baseline with upregulation of LAG3 gene expression, and FOXP3+ CD4+ regulatory T cell population with high expression of CTLA4 and ICOS consistent with inducible Tregs (iTregs) in all, but one baseline sample that did not resolve during treatment (C1D15). Conclusions: Paired scRNA and TCRseq revealed distinctive functional composition of T cells and other immune cells. Combined scRNA expression and scTCR analysis identified malignant from non-malignant T cell subsets. Malignant T cell clones diminished in responders during treatment, while shifted or emerged in non-responders. Clonal enrichment of iTregs and exhausted CD4 and CD8 T cells were identified that did not resolve during treatment. suggesting that potential targeting of ICOS, CTLA4 and/or LAG3 will reverse T cell dysfunction in TILS and iTregs, respectively and increase clinical benefit of anti-PD-L1 blockade. Disclosures Querfeld: Stemline: Consultancy; MiRagen: Consultancy; Kyowa Kirin: Consultancy; Bioniz: Consultancy; Helsinn: Consultancy; Trillium: Consultancy; Celgene: Research Funding. Rosen:Novartis: Consultancy; Pebromene: Consultancy; Aileron Therapeutics: Consultancy; Celgene: Speakers Bureau; paradigm Medical Communications: Speakers Bureau; Abbvie: Speakers Bureau; Seattle Genetics: Consultancy; NeoGenomics: Consultancy.

Description: Background: Cutaneous T-cell lymphoma (CTCL), collectively known as mycosis fungoides (MF) and Sézary syndrome (SS) arises from CD4+ T cells in a background of chronic inflammation. The chronic inflammation fosters the growth of CTCL cells and may facilitate T-cells exhaustion that is characterized by deprived effector function and sustained expression of inhibitory receptors. As a result, malignant CTCL cells escape immune surveillance and are not eliminated. At present, the roles of miRNAs or signaling pathways involved in the expression of immune checkpoints in CTCL has yet to be elucidated. Therefore, this project is aimed to elucidate how immune checkpoints are regulated by miRNAs, and how this regulation contributes to T-cell exhaustion and the development of CTCL. Methods: We first conducted miRNAseq analysis to assess the miRNA profile of 50 CTCL patient tumor samples. The sequencing data analysis was performed at the City of Hope Integrative Genomics Core. Next, we verified the expression of 3 highly upregulated miRNAs (miR-155, -21 and -130) from the miRNAseq analysis in 5 CTCL cell lines and tumor samples using qRT-PCR and in situ hybridization (ISH). Finally, we transfected the CTCL cell line Myla 2059 and HuT 78 with anti-miR-155, -21, -130 or Scramble (Scr) control using the Lonza nucleofection kit and nucleofector machine. Cell lysates were prepared 72 hours after transfection and then subjected to Western Blot analysis. We probed the blot with antibodies against SOCS, PTEN, pSTAT3 and GAPDH as a loading control. Results: The data analysis revealed that miR-155 had the highest correlation with CTLA-4 (r = 0.59, P 〈 0.0001), PD1 (r = 0.42, P = 0.0021), PD-L1 (r = 0.42, P = 0.0025), TIM3 (r = 0.63, P 〈 0.0001), LAG3 (r = 0.57, P 〈 0.0001), and ICOS (r = 0.74, P 〈 0.0001) mRNA; -21 had the highest correlation with PD-L1 (r = 0.44, P = 0.0012), TIM3 (r = 0.52, P 〈 0.0001), and ICOS (r = 0.37, P 〈 0.0073) mRNA; and -130 had the highest correlation with CTLA-4 (r = 0.5, P = 0.0002), PD-L1 (r = 0.54, P 〈 0.0001), TIM3 (r = 0.69, P 〈 0.0001), LAG3 (r = 0.49, P = 0.0003), and ICOS (r = 0.68, P 〈 0.0001) mRNA. qRT-PCR and ISH revealed that miRs-155, -21 and -130 were upregulated in all 5 CTCL cell lines and primary tumor samples. There was a dramatic increase in SOCS proteins and significant decrease in pSTAT3 expression in Myla 2059 and HuT 78 cells transfected with anti-miRs-155, -21 or -130, compared to cells transfected with Scr. Conclusions: Immune checkpoints and ligands like PD-L1 expression in CTCL are regulated by miRs-155, -21 and -130. The SOCS family of proteins, negative regulators of STAT signaling, are involved in miRs-155, -21 and -130-induced immune checkpoints expression in CTCL. Taken together, these results demonstrate the mechanisms of miRNA-induced T cell exhaustion and pave the way for the development of miRNA therapeutics in CTCL. Disclosures Rosen: Seattle Genetics: Consultancy; Celgene: Speakers Bureau; paradigm Medical Communications: Speakers Bureau; Abbvie: Speakers Bureau; NeoGenomics: Consultancy; Aileron Therapeutics: Consultancy; Novartis: Consultancy; Pebromene: Consultancy. Querfeld:Celgene: Research Funding; Stemline: Consultancy; Trillium: Consultancy; MiRagen: Consultancy; Kyowa Kirin: Consultancy; Bioniz: Consultancy; Helsinn: Consultancy.

Description: Relapse of acute myeloid leukemia (AML) is attributed to the persistence of quiescent leukemia stem cells (LSCs). Bcl-2 inhibition has been shown to target primitive leukemia progenitors. Venetoclax (VEN) is a FDA-approved Bcl-2-selective inhibitor for the treatment of AML. Although the activity of single agent VEN in AML patients (pts.) is modest, clinical efficacy in newly diagnosed, older pts. unfit for intense chemotherapy has been shown when VEN is combined with the hypomethylating agents (HMAs) azacytidine and decitabine or with low-dose nucleoside analog cytarabine. We have recently shown that VEN in combination with HMAs augments oxidative stress in AML cells and provided a molecular mechanism for the VEN-HMA-regulated NF-E2-related factor 2 (Nrf2) antioxidant pathway that could explain the results observed in early clinical studies in AML. Although about 70% of pts. initially respond to these VEN treatment regimens, about 30% of pts. do not and diminished efficacy of VEN combination treatments have been observed in pts. harboring poor-prognosis markers such as FLT3-ITD. In addition, future relapse of a percentage of pts. treated with VEN combinations is expected. Thus, novel treatment options for are urgently needed. We previously reported that the ribose containing, RNA-directed nucleoside analog 8-chloro-adenosine (8-Cl-Ado) demonstrates cytotoxic activity against AML cells and LSCs in vitro and in vivo, without significantly affecting normal hematopoietic stem cells. Importantly, our initial, unpublished results from a phase I/II clinical trial with single agent 8-Cl-Ado in pts. with refractory/relapsed AML demonstrate encouraging clinical benefits. Moreover, we have reported that FLT3-ITD AML is particularly sensitive to 8-Cl-Ado, thus suggesting 8-Cl-Ado plus VEN as a potential novel therapeutic regimen for treatment of AML. We here report that the VEN plus 8-Cl-Ado combination inhibited in vitro growth and induced apoptosis in AML primary cells, LSCs and cell lines significantly more compared to treatment with the individual agents. For in vitro cell growth studies, combination indices of

Description: Background: Tumor-associated macrophages (TAMs) play a key role in cutaneous T cell lymphoma (CTCL) growth and neoplastic T cells escape immune surveillance via PD1-PD-L1 axis (Querfeld, C., et al., Blood 2019; Khodadoust, M.S., et al., J Clin Oncol, 2020). There remains a lack of knowledge about how cytokines regulate the mechanisms controlling tumor-growth and polarize the tumor microenvironment (TME). Methods and Results: To investigate PD-L1 and PD1 expression on TAMs and T cells in mycosis fungoides (MF) and the leukemic variant Sézary syndrome (SS) patients, we performed multiplex immunofluorescence (IF) staining of lesional skin samples of MF patients that demonstrated co-localization of PD-L1 on CD163+ M2 macrophages and PD1 expression on CD4+ and CD8+ T cells. In addition, significant enrichment of CD14+ and CD16+/CD14dim CD163+ M2-like monocytes/macrophages with upregulated PD-L1 expression in SS patients compared to healthy donors (HDs) was found via FACS analysis. We also performed 30-plex Luminex cytokine assay on plasma samples, which showed significantly increased IL-6, IL-10, IFNγ and TNFα levels in plasma of MF/SS compared to HDs. To investigate whether polarization towards an M2-like macrophage phenotype with increased PD-L1 expression correlated with the cytokine expression from CTCL-TME, we cultured total PBMCs from HDs with conditioned media (CM) from well established CTCL cell lines MyLa and HuT78 and analyzed PD-L1 mRNA, total PD-L1 protein and PD-L1 surface expression on M2-like macrophages. Significantly increased expression of PD-L1 protein in total PBMCs, especially on CD14+ and CD16+/CD14dim M2-like macrophages was seen. To understand whether distinct cytokines are associated with PD-L1 upregulation on CD163+ M2-like populations, total PBMCs from HDs were stimulated with human recombinant IL-6, IL-10, IFNγ or TNFα. Antibody blocking studies were conducted by adding anti human IL-6, IL-10, IFNγ or TNFα to the cultures with CM. TNFα stimulation significantly increased the CD14+ M2-like subset, but did not affect CD16+/CD14dim M2-like subset. We observed increased PD-L1 expression on both M2-like populations with TNFα compared to other cytokines. In contrast, blockade of TNFα significantly decreased the CD14+ M2-like subset with reduced PD-L1 expression and increased CD16+/CD14dim M2-like cells with upregulated PD-L1 expression. To explore whether the STAT pathway regulates PD-L1 expression through cytokines from CTCL TME, we incubated total PBMCs from HDs in CM of MyLa and HuT78 cells with/without a pan-STAT inhibitor, and in media alone. Inhibition of STAT signaling decreased CD14+ M2-like macrophage population, but did not alter the CD16+/CD14dim M2-like population. In addition, pan-STAT inhibition significantly reduced surface expression of PD-L1 on both CD14+ and CD16+/CD14dim M2-like macrophages. The effects of cytokines on STAT signaling components in regulating PD-L1 expression were also investigated by FACS and immunoblots. TNFα blockade significantly downregulated PD-L1, but also pSTAT1, pSTAT3 and pNF-κB levels, illustrating the role of TNFα on STAT1, STAT3 and NF-κB pathways in conjunction with PD-L1 expression. Stimulation with TNFα increased pSTAT3 level in CD14+ M2-like macrophages, while it did not significantly change pSTAT3 in CD16+/CD14dim M2-like macrophages. Anti-TNFα reduced pSTAT3 levels in CD14+ M2-like macrophages, but profoundly increased PD-L1 in CD16+/CD14dim M2-like macrophages, which aligns with our data of increased PD-L1 expression on CD16+/CD14dim M2-like macrophages following TNFα blockade. Conclusion: We profiled immune alterations of monocyte/macrophages populations and PD-L1 expression in CTCL regulated by selected cytokines. Our results support the dominant role of TNFα in the CTCL microenvironment. Here we show that TNFα potentiates the immunosuppressive TME through macrophage polarization and STAT-mediated PD-L1 regulation. Our results identify potential targets for combination immunotherapy. Disclosures Zain: Seattle Genetics: Research Funding; Mundai Pharma: Research Funding; Kyowa Kirlin: Research Funding. Abdulla:Johnson Johnson: Research Funding; Mallinckrodt: Consultancy, Speakers Bureau. Rosen:Seattle Genetics: Consultancy; NeoGenomics: Consultancy; Aileron Therapeutics: Consultancy; Novartis: Consultancy; Pebromene: Consultancy; Celgene: Speakers Bureau; Abbvie: Speakers Bureau; paradigm Medical Communications: Speakers Bureau. Querfeld:Trillium: Consultancy; Stemline: Consultancy; Bioniz: Consultancy; Helsinn: Consultancy; Celgene: Research Funding; Kyowa Kirin: Consultancy; MiRagen: Consultancy.

Description: Background:T cells in CTCL 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. We initiated a phase 1/2 clinical trial of lenalidomide and durvalumab (NCT03011814) to determine the safety and efficacy of this regimen. Durvalumab is a human monoclonal antibody with high affinity and selectivity for PD-L1, targeting exhausted T cells and distinct cells within their environment. Lenalidomide, an oral immunomodulatory drug (IMiD) 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. Associations between immune checkpoints, gene expression profile and the clinical efficacy of durvalumab/ lenalidomide combination were evaluated. The primary objectives were to determine the recommended phase 2 dose of lenalidomide in combination with durvalumab and safety with primary endpoint of toxicity (using CTCAE 4.03). Secondary end points included objective response rate (ORR) and median duration. Relationships between gene expression profile (GEP), PD-L1 expression, and antitumor activity were exploratory end points. Methods:Phase 1 portion to evaluate the safety and tolerability of the durvalumab and lenalidomide combination has completed enrollment. Pts were enrolled in sequential cohorts to receive durvalumab (fixed dose at 1500 mg) and dose escalation of lenalidomide (dose level 1 = 10 mg for all cycles; dose level 2 = 10 mg for cycle 1, 15 mg for all subsequent cycles; dose level 3 =10 mg for cycle 1, 15 mg for cycle 2, and 20 mg for all subsequent cycles) to characterize safety, efficacy and antitumor activity. Serial skin samples were collected to assess the impact on the tumor microenvironment and anti-tumor activity. Results:Thirteen pts. were evaluable for toxicities and 12 patients evaluable for response. 10 males/3 females, median age 36 (29-72 y), with aggressive or refractory/advanced CTCL, clinical stages IB (2), IIA (3), IIB (6), IIIA (1), and aggressive epidermotropic CD8+ CTCL (1) and a median of prior systemic treatments of 3 (range, 2-8) have been enrolled. Dose level 1 (n=3), dose level 2 (n= 3), dose level 3 (n=4). Median follow up time was 16.1 months (range, 3.7-36.1) months. No serious AEs or DLTs were observed during the DLT evaluation period (cycles 1-3). The most frequently reported AEs were fatigue (n=8), skin pain (n=4), chills (n=3), anemia (n=3), and leukopenia (4). One grade 3 maculopapular rash (possibly due to lenalidomide) was observed, all other treatment-related AEs were grade 1/2 in severity. One patient discontinued treatment due to fatigue. Three patients developed grade 1/2 autoimmune thyroiditis that resolved with treatment. Median cycles of treatment were 7 (range, 1-28). Median duration of response was 6 (range, 1- 28+) months. Nine pts achieved PR, 2 pts maintained stable disease and 2 pts developed PD. Five pts remain on treatment. Gene expression levels for several checkpoints (PD1, PD-L1 & ICOS) (Cycle1 Day1 vs Cycle 2 Day15) were analyzed. Gene expression profile highlights downregulation of TNF-alpha signaling via NFkB, IFN-gamma, and PI3-AKT-mTOR signaling pathways in responders; up-regulation of MYC targets, IL2-, JAK-STAT and pro-inflammatory pathways were seen in PD compared to responders. Conclusions:Anti-PD-L1/lenalidomide has significant clinical activity in refractory/advanced CTCL, which will be formally evaluated in the Phase 2 portion. Responses were durable and ongoing, and treatment was well tolerated. Dose escalation is up to maximum dose of 20 mg lenalidomide daily. Our preliminary results reveal adaptive and innate immune signatures that may be predictive of response to checkpoint blockade and yield insights into mechanisms of therapeutic resistance. Disclosures Querfeld: MiRagen:Consultancy;Stemline:Consultancy;Trillium:Consultancy;Celgene:Research Funding;Kyowa Kirin:Consultancy;Helsinn:Consultancy;Bioniz:Consultancy.Abdulla:Johnson Johnson:Research Funding;Mallinckrodt:Consultancy, Speakers Bureau.Rosen:Seattle Genetics:Consultancy;NeoGenomics:Consultancy;Aileron Therapeutics:Consultancy;Novartis:Consultancy;Pebromene:Consultancy;Celgene:Speakers Bureau;paradigm Medical Communications:Speakers Bureau;Abbvie:Speakers Bureau.Zain:Mundi Pharma:Research Funding;Seattle Genetics:Research Funding;Kyowa Kirin:Research Funding.

Description: Aberrant mRNA processing is known to drive the pathogenesis of chronic lymphocytic leukemia (CLL). Recurrent gene mutations in the RNA splicing factor SF3B1 and widespread RNA intronic polyadenylation impact genome-wide gene expression and inactivate tumor suppressors, respectively. Nevertheless, how mRNA processing is regulated and exerts its function in CLL remain elusive. To comprehensively characterize the role of mRNA processing in CLL, we performed RNA sequencing (RNA-seq) and Tandem Mass Tag (TMT) proteomics using normal and CLL B cells derived from healthy donors (n=5) and untreated CLL patients (n=22). We detected 328 proteins differentially expressed between normal and CLL B cells (|Log2FC|〉0.58, q

Description: Introduction: Standard of care for patients (pts) with relapsed or refractory (RR) Hodgkin lymphoma (HL) is salvage therapy (tx) followed by autologous hematopoietic cell transplantation (HCT). However, most pts with high-risk RR HL will relapse after HCT. The AETHERA study demonstrated that post-HCT consolidation with brentuximab vedotin (BV) in high-risk HL pts improved progression-free survival (PFS) compared to placebo, particularly in pts with 2+ risk factors (Moskowitz, 2018). Pts with prior BV exposure were excluded from AETHERA, and BV is increasingly used prior to HCT in HL. PD1 blockade is effective in pts with RR HL and PD1 monotherapy as post-HCT consolidation in HL resulted in promising 18 mo PFS (Armand, 2019). Combined BV and nivolumab (Nivo) is a safe and effective salvage tx in HL, therefore we conducted a multicenter phase 2 study to evaluate the safety and efficacy of BV-Nivo post-HCT consolidation in high risk RR HL. Methods: After HCT, adult pts with high-risk HL defined as having ≥ 1 of the following modified AETHERA risk factors were eligible: primary refractory HL, relapse 〈 1 year of completing initial tx, extranodal disease (dz) at relapse, B symptoms (sx) at relapse, requiring 〉 1 salvage tx, not in CR at HCT. Prior BV or PD1 blockade were allowed if pts were not refractory. Pts underwent HCT according to institutional standards at the 5 centers. Starting between day 30-75 after HCT, pts received 1.8 mg/kg of BV and 3mg/kg nivo q21 days for a planned 8 cycles. If 1 drug was discontinued due to toxicity, the other could be continued. Investigators assessed response and progressive disease (PD) according to the 2014 Lugano classification. The primary endpoint was 18 mo PFS from study tx initiation. Secondary endpoints were overall survival (OS), safety, and the response rate in pts not in complete response (CR) at baseline. Results: 59 pts were enrolled and treated with at least one dose of study tx. Baseline characteristics are listed in Table 1. 18 (31%) pts were primary refractory, 35 (59%) had early relapse, 23 (39%) had extranodal dz and 14 (24%) had B sx at relapse, 15 (25%) received 〉 1 salvage tx before HCT, and 48 (81%) were in CR at HCT. 21 (36%) had 1 modified AETHERA risk factor, 23 (40%) had 2 and 14 (24%) had 3+ risk factors. The median follow-up time from study tx initiation was 15.7 months (range, 2.8-35.5). Patients initiated BV-nivo a median 54 days from HCT (range, 34-75) and received a median of 8 cycles (range, 1-8). 29 (49%) pts completed all 8 cycles of BV and nivo and 45 (76%) patients completed 8 cycles of one drug. 14 (24%) pts discontinued both BV and nivo early, including 6 for adverse events (AE), 6 pt withdrawals, 1 pt lost to follow-up, and 1 pt death from PJP pneumonia unrelated to study tx. BV was discontinued in 8 (14%) pts - due to grade (gr) 3 peripheral neuropathy (PN) in 2 pts, gr 2 PN in 2 pts, carpal tunnel syndrome in 1 pt, gastrointestinal AEs in 2 pts, and infusion related reaction in 1 pt. Nivo was discontinued in 7 (12%) pts - due to pneumonitis in 2 pts, and colitis, elevated bilirubin, abnormal transaminases, pneumonia with elevated creatinine, and hypotension with fever in 1 pt each. BV was dose reduced to 1.2mg/kg in 11 (19%) pts, 9 pts for PN, and 1 each for neutropenia and arthralgia. The most common AEs related to BV-Nivo consolidation were PN (51%, 3% gr 3), neutropenia (42%, 31% gr 3-4), fatigue (37%), diarrhea (29%, 3% gr 3), nausea (25%, 2% gr 3), arthralgia (24%), AST elevation (24%, 2% gr 3). The most frequent gr 3-4 AEs were neutropenia (31%), pneumonitis (7%), and ALT elevation (5%). Immune-related (ir) AEs requiring systemic corticosteroids occurred in 18 (31%) patients. Most common Gr 2 or higher irAEs included: pneumonitis (12%), AST or ALT elevation (8%), hypothyroidism (5%), and rash (3%). 6 pts were not in CR at baseline after HCT (all PR). 5 pts converted to CR with study tx and 1 pt remained in PR without PD. There were only 2 PFS events, 1 pt with relapse at 15 months and PJP-related death after prophylaxis was self-discontinued. The estimated 18 mo PFS and OS in all patients were 95% and 98%, respectively. The estimated 18 mo PFS in pts with 2+ and 3+ risk factors were 92% and 89%, respectively. Conclusions: Post-HCT consolidation with BV-Nivo in pts with high-risk RR HL is a promising approach, with only 1 relapse observed in our cohort with short follow-up thus far. Post-HCT BV-Nivo was tolerable, though IrAEs were observed more frequently than in the pre-HCT setting and PN and neutropenia were common. Disclosures Herrera: Pharmacyclics: Research Funding; Karyopharm: Consultancy; AstraZeneca: Research Funding; Gilead Sciences: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Nieto:Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support. Holmberg:Sanofi: Research Funding; Seattle Genetics: Research Funding; Millenium-Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; UpToDate: Patents & Royalties: Royalties; Janssen: Research Funding; Merck: Research Funding. Mei:Sanofi: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees. Chen:Autolus Therapeutics: Current Employment. Rosen:Abbvie: Speakers Bureau; Seattle Genetics: Consultancy; NeoGenomics: Consultancy; Aileron Therapeutics: Consultancy; Novartis: Consultancy; Pebromene: Consultancy; Celgene: Speakers Bureau; paradigm Medical Communications: Speakers Bureau. Kwak:CJ Healthcare: Consultancy; Xeme Biopharma/Theratest: Other: equity; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. Feldman:Portola: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Trillium: Research Funding; Janssen: Speakers Bureau; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; AstraZeneca: Consultancy. OffLabel Disclosure: Nivolumab is not FDA-approved for use as consolidation after autologous stem cell transplantation