ALBERT

Description: Background: Autologous stem cell transplantation (ASCT) can be curative for patients (pts) with relapsed/refractory Hodgkin lymphoma (HL) who are sensitive to salvage therapy, particularly for pts who achieve a complete metabolic response (CMR) before ASCT. Pts who fail multiple salvage regimens have inferior outcomes and are generally considered poor candidates for ASCT. Recent studies suggest that anti-PD-1 monoclonal antibodies (mAbs) may restore sensitivity to cytotoxic therapy in HL pts with previously chemorefractory disease. We hypothesized that PD-(L)1 mAb-based salvage therapy may therefore also improve ASCT outcomes for HL pts who had failed salvage therapy. Methods: Medical records were reviewed at 13 US transplant centers to identify pts with a diagnosis of classic HL who failed at least 2 systemic therapies, were treated with a PD-1 or PD-L1 mAb (either alone or in combination) as 3rd line or later therapy, and subsequently underwent ASCT. Results: 44 eligible pts were identified. The median age was 33 (range 19-68). Pts received ABVD (39), AVD (2), brentuximab vedotin (BV) + AVD (1), Stanford V (1), or eBEACOPP (1) as 1st line therapy. 26 pts (59%) were refractory to 1st line treatment and 8 additional pts (18%) relapsed within 12 months. High-risk clinical features were observed frequently at 1st relapse including extranodal involvement (47%), B symptoms (27%), and advanced stage (64%). Pts received PD-(L)1 based treatment after failing 2 lines (32%), 3 lines (57%), or ≥4 lines (11%) of therapy. 32 pts (73%) were refractory to the line of therapy before PD-(L)1, 25 pts (57%) to 2 consecutive lines before PD-(L)1, and 10 pts (22%) to 3 consecutive lines before PD-(L)1. 16 pts (36%) were refractory to ≥2 salvage therapies immediately before PD-(L)1 therapy and 17 (39%) were refractory to all prior treatments. 39 pts (89%) received BV or a BV-based combination before ASCT. 67% were BV-refractory, including 86% of those receiving BV monotherapy. Pts received a median of 6 doses of a PD-(L)1 mAb (range 2-26) either as monotherapy (75%) or as part of a PD-1 based combination (25%). The median time from last dose of PD-(L)1 mAb to ASCT was 54 days (range 12-386). Best response to PD-(L)1-based therapy was CR (53%), PR (33%), SD (12%), or PD (2%). The median number of systemic therapies (including PD-(L)1) before ASCT was 4 (range 3-7) and 12 pts (27%) received intervening salvage therapy between PD-(L)1 treatment and ASCT. Pre-ASCT PET status was CR in 31 pts (70%), PR in 9 (18%), SD in 4 (9%), and PD in 1 (2%). There were no ASCT-related deaths. 2 pts developed BCNU pneumonitis and 1 developed engraftment syndrome. All 3 pts responded to steroids. 14 pts (32%) have received maintenance therapy with BV (4), a PD-1 mAb (8), or BV + PD-1 mAb (2). 4 pts (9%) received consolidative radiation. With a median post-ASCT follow-up of 12.2 months, progression-free survival (PFS) at 1 yr was 91% [95CI 75-97]. Notably, resistance to chemotherapy before PD-(L)1 therapy did not predict worse post-ASCT outcomes (see Table). 1-yr PFS was 90% for pts who were refractory to the 3 lines of therapy before PD-(L)1, 93% for pts refractory to ≥2 salvage therapies immediately before PD-(L)1, and 90% for pts refractory to all prior treatments. Favorable 1-yr PFS was also seen among pts who received PD-(L)1 as 4th or later line therapy (88% vs 100% for pts receiving PD-[L]1 as 3rd line, p=0.17) and among pts who failed to achieve a CMR on pre-ASCT PET (1-yr PFS 81% vs 96% for CMR pts, p=0.34). Lack of response to PD-(L)1 therapy (1-yr PFS 67% vs 96%, p=0.04), receipt of intervening salvage therapy (1-yr PFS 72% vs 100%, p=0.026), and increasing age (HR 1.11, p=0.015) were all significant predictors of inferior PFS. 1-yr overall survival was 100%. Conclusions: This high-risk cohort is heterogenous in terms of number of prior therapies and degree of chemoresistance, but excellent post-ASCT outcomes were observed among even the most heavily pre-treated, chemorefractory subgroups. Outcomes for PD-(L)1 responders were particularly favorable with a 1-yr PFS of 96%, suggesting that response to PD-(L)1 rather than prior chemotherapy may be the more important predictor of post-ASCT outcomes in this pt population. While longer follow-up is required to confirm the durability of these remissions, ASCT can be considered for HL pts responding to PD-(L)1 based salvage therapy, even if they have previously demonstrated a high degree of chemoresistance. Table Disclosures Nieto: Novartis: Research Funding; Astra-Zeneca: Research Funding; Affimed: Research Funding; Affimed: Consultancy. Byrne:Karyopharm: Research Funding. Maddocks:BMS: Research Funding; Novartis: Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding. Svoboda:BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. McGuirk:Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Research Funding; Fresenius Biotech: Research Funding; Astellas: Research Funding; Bellicum Pharmaceuticals: Research Funding. Advani:Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Millennium: Research Funding; Janssen: Research Funding; Cell Medica, Ltd: Consultancy; Regeneron: Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stanford University: Employment, Equity Ownership; Agensys: Research Funding; Kura: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding; Infinity Pharma: Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy. Frigault:Xenetic: Consultancy; Foundation Medicine: Consultancy; Novartis: Consultancy; Nkarta: Consultancy; Juno/Celgene: Consultancy; Kite/Gilead: Honoraria; Incyte: Consultancy. Chen:Magenta: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Kiadis: Consultancy; Abbvie: Consultancy. Lynch:Johnson Graffe Keay Moniz & Wick LLP: Consultancy; Rhizen Pharmaceuticals S.A: Research Funding; Juno Therapeutics: Research Funding; Takeda Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; T.G. Therapeutics: Research Funding. Smith:Seattle Genetics: Research Funding; Denovo Biopharma: Research Funding; Ayala (spouse): Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Incyte Corporation: Research Funding; Ignyta (spouse): Research Funding; Genentech: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Armand:Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sigma Tau: Research Funding; Infinity: Consultancy; Otsuka: Research Funding; Genentech: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Herrera:Merck: Consultancy; BMS: Consultancy; Genentech: Research Funding; Adaptive Biotechnologies: Consultancy; Gilead Sciences: Research Funding; KiTE/Gilead: Consultancy; Genentech: Consultancy; Merck: Research Funding; Astra-Zeneca: Research Funding; Seattle Genetics: Consultancy; BMS: Research Funding; Seattle Genetics: Research Funding.

Description: Background: Outcomes to salvage therapy for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) are suboptimal. Checkpoint blockade therapy (CBT) has been explored in the relapsed/refractory (R/R) NHL population, but response rates to single agent CBT therapy are modest. To date, there is no literature on whether treatment with CBT may sensitize NHL patients to subsequent therapy. We investigated the outcome of subsequent treatment in patients with R/R NHL who had received CBT in a large multicenter international retrospective analysis. Methods: Seventeen centers across the US and Canada are participating in this study to date. Medical records of each institution were queried to identify lymphoma patients who received CBT and were subsequently treated with an additional line of therapy. The primary aim of the current analysis was to determine the best response to post-CBT treatment in patients who discontinued CBT due to progression of disease (PD) or toxicity. Patients who discontinued CBT due to a complete response (CR), or patients whose best response to post-CBT therapy could not be determined due to death from another cause, were excluded from analysis. Responses were assessed using Lugano criteria. Survival status to date was analyzed for the entire study population and stratified by post-CBT treatment regimen categories and disease subgroups using the Kaplan-Meier method. Progression free survival (PFS) and overall survival (OS) were calculated for patients with at least stable disease (SD) to post-CBT treatment. Log rank tests were performed to test for statistical significance. Two-sided P

Description: Introduction: Non-myeloablative conditioning with total lymphoid irradiation and antithymocyte globulin (TLI-ATG) is associated with a low risk of graft-versus-host disease (GVHD), attributed to skewing of residual host T-cell subsets to favor regulatory IL-4 producing natural killer T cells that polarize the infused donor T cells to a Th2 phenotype, while retaining graft-versus-tumor (GVT) reactions in lymphoid and myeloid malignancies. We hypothesized that the safety of TLI-ATG conditioning with its protection from GVHD would extend beyond matched donors, yet with mismatching there would be at least as potent GVT reactions as with matched donors. We therefore compared outcomes in patients who received TLI-ATG conditioning and allogeneic hematopoietic cell transplantation (HCT) from HLA-mismatched unrelated donors to those with HLA-matched unrelated donors. Methods: Patients: We included all consecutively transplanted patients at Stanford University Hospital from December 2001 through May 2015 who received TLI-ATG conditioning and allogeneic HCT from 10/10 HLA-matched unrelated donors (MUD, N=193) or HLA-mismatched unrelated donors (mmUD, N=72), including 70 patients matching in 9/10 alleles or antigens (55 mismatched at HLA-A, -B, -C or -DRB1 loci and 15 mismatched at HLA-DQB1) and 2 patients matched in 8/10 alleles. All patients received G-CSF-mobilized peripheral blood hematopoietic cells and cyclosporine and mycophenolate mofetil for GVHD prophylaxis. Statistical methods: For time-to-event analyses, Kaplan-Meier curves were used to estimate survival and cumulative incidence of acute and chronic GVHD, non-relapse mortality, and relapse. Log-rank tests were used to detect differences between groups. Results: Median age at the time of transplant was 60 years in both groups (range 21-76) with a median follow up of 677 days (range 53-3682) in the mmUD cohort and 762 days (range 37-4551) in the MUD cohort. There were no significant differences between the mmUD and MUD cohorts in underlying diagnosis (acute myeloid leukemia 32% vs 31%, non-Hodgkin lymphoma 22% vs 29%, chronic lymphocytic leukemia 17% vs 17%, myelodysplastic syndrome and myeloproliferative neoplasms 11% vs 14%, Hodgkin lymphoma 8% vs 5%; chronic myeloid leukemia 7% vs 2%, and acute lymphoblastic leukemia 3% vs 3%).The majority of patients in both mmUD and MUD cohorts had advanced stage lymphoid disease (75% vs 72%) and advanced stage myeloid disease (53% vs 54%), defined as disease status beyond second complete remission at the time of transplant, relapse following prior autologous or allogeneic transplant, high-risk cytogenetic abnormality and age over 55, myelodysplastic syndrome with progression to acute myeloid leukemia, or therapy-related myeloid neoplasm. Durable chimerism was achieved in 90% of patients in the mmUD group and 94% of patients in the MUD group. There were no significant differences between the mmUD and MUD cohorts in the cumulative incidence of acute GVHD at day +100 (grades II-IV: 21% vs 15%, p=0.78 and grades III-IV: 6% vs 3%, p=0.61). Non-relapse mortality (NRM) was not significantly different (14% at 1 year in mmUD group vs 6% in MUD group, p=0.34). There was no significant difference in the cumulative incidence of chronic GVHD (31% vs 27% at 2 years and 39% vs 35% at 5 years, p=0.49). There was a trend towards a lower rate of relapse in the mmUD group (40% vs 48% at 2 years, 45% vs 60% at 5 years, hazard ratio 0.71, p=0.094). There was no significant difference in overall survival (58% vs 60% at 2 years and 46% vs 46% at 5 years) or event-free survival (46% vs 44% at 2 years and 38% vs 28% at 5 years, p=0.25). In both groups, sustained remissions occurred among patients with active disease at the time of transplantation. Conclusions: TLI-ATG conditioning is associated with low rates of acute and chronic GVHD and NRM even in the setting of HLA-mismatched unrelated donor transplantation. There was a particularly low incidence of severe acute GVHD grades III-IV (3-6%) in this high-risk cohort. The trend towards lower relapse in recipients of HLA-mismatched grafts may reflect enhanced GVT reactions. TLI-ATG conditioning may overcome the traditionally poorer outcome and high NRM associated with HLA mismatch and should be considered in patients with advanced lymphoid and myeloid malignancies who cannot tolerate myeloablative preparatory regimens and who lack a fully HLA-matched donor. Figure 1 Figure 1. Disclosures Meyer: Stanford University: Patents & Royalties. Negrin:Stanford University: Patents & Royalties.

Description: Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation. Herpesvirus infection is a common trigger of HLH, and in some patients may indicate an underlying immunodeficiency. Primary immunodeficiencies associated with HLH are often characterized by impaired cytotoxic function of NK cells and/or cytotoxic T lymphocytes and include Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes and the X-linked lymphoproliferative disorders, SAP and XIAP deficiency. GATA2 deficiency, also known as MonoMAC syndrome, is a primary immunodeficiency resulting from haploinsufficiency of the GATA2 transcription factor, a master regulator of hematopoiesis. Clinically, GATA2 deficiency is characterized by progressive cytopenias of monocytes, dendritic cells, and B and NK lymphocytes; susceptibility to infection with human papillomavirus, herpesviruses, nontuberculous mycobacteria, and invasive fungi; and bone marrow failure with risk for clonal evolution to myelodysplastic syndrome and acute myelogenous leukemia. Additional manifestations may include pulmonary alveolar proteinosis, congenital lymphedema, and sensorineural hearing loss. We report two patients with GATA2 deficiency/MonoMAC syndrome who developed aggressive HLH in the setting of marked NK cell dysfunction and disseminated herpesvirus infection. Case 1 The patient was an African-American female with severe bilateral lymphedema since age 9 requiring multiple hospitalizations for lymphedema cellulitis. At age 12, she was hospitalized for severe pulmonary blastomycosis with necrotizing pneumonia. An immunologic workup revealed profound monocytopenia and B and NK lymphocytopenia, and NK functional testing revealed markedly reduced cytotoxicity and near absence of the CD56(bright) subset. Genetic testing for mutations in PRF1, UNC13D, and STX11 was negative. At age 18, she presented with septic shock and persistent fevers despite empiric antibiotics, and HSV-1 DNA was detected in the blood. The diagnosis of MonoMAC syndrome was strongly suspected in light of her congenital lymphedema and highly characteristic cytopenias and infections. Unfortunately, she rapidly decompensated and developed massive hyperferritinemia, hypofibrinogenemia, pancytopenia, and fulminant hepatitis concerning for HSV-1-driven HLH. An autopsy following her death revealed disseminated HSV-1 infection in the lungs, liver, and genitalia, and a hypocellular bone marrow with hemophagocytosis. The cause of death was HLH in the setting of NK cell deficiency and widespread HSV-1 infection. Genetic testing for GATA2 mutation was performed posthumously and is currently in progress. Case 2 A Chinese female presented at age 20 with persistent fevers, cervical lymphadenopathy, and cutaneous ulcers. Mycobacterium avium complex was identified in the sputum and urine, and she was treated with clarithromycin, rifampin, and ethambutol. HIV testing was negative. Biopsy of her skin lesions revealed an EBV+ hydroa vaccineforme-like cutaneous T-cell lymphoma, and she was found to have significant EBV viremia with over 1 million copies/mL detected by quantitative PCR. An immunologic workup revealed profound B and NK lymphocytopenia. Monoallelic GATA2 mRNA expression was demonstrated leading to haploinsufficiency. She developed persistent fevers, worsening hyperferritinemia, hypofibrinogenemia, pancytopenia, and transaminitis. Bone marrow biopsy revealed a hypocellular marrow with EBV+ T cells and abundant hemophagocytosis. She was diagnosed with EBV-driven HLH and was treated with etoposide and dexamethasone followed by nonmyeloablative, haploidentical related donor stem cell transplant. She is currently 12-months post-transplant with an undetectable EBV viral load and complete resolution of her T cell lymphoma and HLH. Conclusion GATA2 deficiency is associated with NK cell dysfunction and disseminated herpesvirus infection, which can lead to aggressive HLH. Genetic testing for GATA2 mutation should be considered in patients with HLH and underlying NK cell deficiency and/or herpesvirus infection. NK functional testing typically shows markedly reduced cytotoxicity and near absence of the CD56(bright) subset. Allogeneic transplant represents a potentially curative approach in this setting. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) are clonal myeloid neoplasms for which limited conventional treatment options exist in the relapsed / refractory setting, especially for older patients. Methods: We provide proof of concept data by drug sensitivity profiling of 64 samples from 52 adult patients with both newly diagnosed and treatment refractory myeloid neoplasms (MDS = 38, CMML = 4, AML = 10). Fresh mononuclear cells from bone marrow aspirates and/or peripheral blood specimens were red blood cell lysed upon arrival and re-suspended in serum free media with cytokines. The samples were then plated in 384 well microtiter plates and were screened against a collection of investigational and FDA approved compounds (up to 85) in triplicate using a Labcyte Echo acoustic liquid handler. These specimens were treated for 72 hours and analyzed for drug sensitivity on an Intellicyt iQue Screener PLUS flow cytometer for both cytotoxicity and differentiation. Results: Principal component analysis was performed to explore differential ex vivo sensitivity and resistance patterns between the MDS and AML samples. Individual MDS samples clustered according to their ex vivo responses, with distinct subgroups enriched for sensitivity to hypomethylating agents (HMAs), HDAC inhibitors, differentiation agents, and PARP inhibitors. Strong clustering of drug classes was also observed with distinct drug classes showing high correlation within samples. Clinical parameters contributed but did not explain all of the variability of ex vivo sensitivity patterns, including prior HMA therapy, cytogenetics, prognostic risk category and mutational profile. In patients resistant to or relapsed from HMAs where next line of treatment matched profiled compounds (n = 19), ex vivo drug sensitivity data demonstrated positive (PPV) and negative predictive values (NPV) of 85% and 83%, respectively, for clinical response prediction (Fisher's exact test p-value = 0.0095). In patients with serial samples, ex vivo sensitivity data corresponded to emergence of clinical resistance. Conclusions: This novel platform, applied to predict ex vivo therapeutic responses of patient samples to various classes of drugs, recapitulates known clinical and molecular predictors of therapeutic efficacy and provides possible new biologically focused therapeutic options. The accuracy and reproducibility of this method coupled with short turnaround time demonstrate the potential of such an approach as a decision support system for therapeutic selection in the management of various myeloid neoplasms. A prospective study is ongoing to assess the feasibility of this technique for treatment decision support purposes in HMA-refractory MDS patients. Disclosures Aleshin: Mission Bio, Inc.: Consultancy; Natera, Inc.: Employment. Santaguida:Notable Labs: Employment. Patterson:Notable Labs: Employment. Gekas:Notable Labs: Employment. Schaffert:Notable Labs: Consultancy.

Description: Background: Autologous stem cell transplantation (ASCT) is a curative therapy for a significant proportion of patients with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL). We previously developed a conditioning regimen for R/R cHL patients undergoing ASCT incorporating gemcitabine and vinorelbine (GN-BVC), which enabled a reduction in the BCNU dose and toxicity without compromising efficacy (BBMT 2010;16:1145-54). Since this publication, several novel agents have been approved for treatment of R/R cHL including brentuximab vedotin (BV) and the immune checkpoint inhibitors (ICIs), which may be changing outcomes and toxicities following ASCT. We sought to determine whether post-ASCT outcomes have improved for R/R cHL in the era of novel agents, and to evaluate how BV and the ICIs have impacted toxicities after ASCT in a large cohort of patients treated with the same conditioning regimen. Methods: We conducted a single-center, retrospective analysis of outcomes for a large cohort of patients with R/R cHL who underwent ASCT using GN-BVC conditioning at Stanford University from 2001-2017 (n=268). We divided the cohort into two treatment eras: Era A: 2001-2009 (n=137) and Era B (increasing use of novel agents): 2010-2017 (n=131). We used Kaplan-Meier and Cox models to compare overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) between treatment eras. We also compared outcomes between patients who underwent ASCT in complete remission (CR, n=126) or with a partial response (PR, n=142). For patients treated in era B, we compared outcomes and toxicity profiles for patients treated with standard platinum-based salvage regimens (n=102) to those who received BV-based salvage regimens prior to ASCT (n=29). Results: Patients who underwent ASCT in era B had improved OS compared to those transplanted in era A (4-year OS: 87.8% vs 77.9%, HR 0.51, 95% CI 0.28-0.91, p=0.022), but PFS did not differ significantly between treatment eras (4-year PFS: 70.2% vs 62.7%, HR 0.78, 95% CI 0.52-1.2, p=0.24, Figure 1). For patients who relapsed after ASCT, PPS was significantly higher for those transplanted in era B compared to era A (84.7% vs 62.8% at 2 years, HR 0.47, 95% CI 0.23-0.98, p=0.045). Overall, patients who underwent ASCT in CR compared to those with a PR had significantly improved OS (88.3% vs 78.3% at 4 years, HR 0.50, 95% CI 0.29-0.88, p=0.016) and PFS (78.4% vs 55.1% at 4 years, HR 0.44, 95% CI 0.28-0.67, p=0.00016). Among patients who relapsed, those in era B who received novel agents (BV and/or an ICI) at any point in treatment exhibited higher OS compared to historical controls in era A (4-year OS: 72.2% vs 53.1%) but were statistically different only at the p=0.083 level which is above the p=0.05 significance threshold. Of the patients who underwent ASCT in era B (n=131), 102 (78%) received standard platinum-based salvage regimens (e.g. ICE or DHAP) and 29 (22%) received BV-based salvage regimens prior to ASCT, including 11 patients (8%) who received both BV and an ICI pre-ASCT. Outcomes were excellent for patients who received BV-based salvage regimens pre-ASCT (4-year OS 97% and PFS 76%) but were not statistically different compared to patients who received platinum-based regimens (4-year OS 86% and PFS 69%; p=0.56 and p=0.76, respectively). Pneumonitis requiring corticosteroids occurred in 8% of patients treated in era B, including 10% of patients receiving BV-based salvage regimens pre-ASCT and 7% of patients receiving standard platinum-based regimens. One patient who received BV and nivolumab pre-ASCT died from grade 5 pneumonitis. Conclusions: In this cohort of R/R cHL patients who underwent ASCT using the same conditioning regimen, OS was significantly higher for patients transplanted within the past decade. A potential survival benefit was observed among patients who relapsed post-ASCT, likely reflecting the more widespread use of BV and ICIs in the post-ASCT setting. Patients who received BV-based salvage regimens pre-ASCT had excellent outcomes without an apparent increase in toxicity, but the small number of patients limits comparisons to standard platinum-based regimens. Further studies are needed to better define the optimal sequencing of novel agents and ASCT in the treatment of R/R cHL in the modern era. Figure 1 Disclosures Sica: Physician's Education Resources (PER): Honoraria. Advani:Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cell Medica, Ltd: Consultancy; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Regeneron: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Agensys: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kura: Research Funding; Merck: Research Funding; Infinity Pharma: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Forty-Seven: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding. Miklos:AlloGene: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotech: Membership on an entity's Board of Directors or advisory committees; Becton Dickinson: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Muffly:Pfizer: Consultancy; Adaptive: Research Funding; KITE: Consultancy. Rezvani:Kaleido: Membership on an entity's Board of Directors or advisory committees, Other: one-time compensation from advisory boards; Nohla Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: one-time compensation from advisory boards; AbbVie: Other: Principal investigator ; U.S. Department of Justice: Other: Expert medical witness; Johnson & Johnson: Employment, Other: Brother is employed. Shizuru:Forty Seven Inc: Equity Ownership, Patents & Royalties.

Description: Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of 〉 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.

Description: Background Myelodysplastic syndrome (MDS) patients who are refractory to hypomethylating agents (HMAs) have a poor prognosis with median survival

Description: Background: Relapsed or refractory (R/R) Hodgkin lymphoma (HL) remains a significant clinical problem. Recently checkpoint blockade therapy (CBT) has shown striking activity in this setting, but the complete response (CR) rate is modest. Patients who relapse after CBT have limited therapeutic options. A prior, retrospective study showed that after anti-PD-1 therapy the objective response rate to chemotherapy alone was 61% (Rossi et al 2017). We investigated the effect of treatment subsequent to CBT in a large international multicenter retrospective analysis. Methods: Seventeen centers across the US and Canada are participating in this study to date. Medical records of each institution were queried to identify HL patients who received CBT and were subsequently treated with an additional line of therapy. The primary aim of this analysis was to determine the best response to post-CBT treatment in patients who discontinued CBT due to progression of disease (PD), preparation for stem cell transplant (SCT), or toxicity. Patients who discontinued CBT due to CR, and patients whose best response could not be determined due to death from another cause were excluded from analysis. Responses were assessed using Lugano criteria. Survival status was analyzed for the entire study population and stratified by post-CBT treatment regimen and disease subgroups using the Kaplan-Meier method. Progression free survival (PFS) was calculated for patients with at least stable disease (SD) to post-CBT treatment. Log rank tests were performed to test for statistical significance. Two-sided P

Description: Introduction: A positive interim PET scan (PET2) following 2 cycles of ABVD for Hodgkin lymphoma (HL) is associated with a poor prognosis; several studies in advanced stage demonstrate benefit from escalating therapy. Definition of positivity (Deauville 3 (D3) vs Deauville 4/5 (D4/5)), initial treatment and response adaptive decisions may vary among clinicians. Data examining practice patterns in managing positive PET2 scans is lacking. We report practice patterns and outcomes for patients (pts) with positive PET2 results including D3 and D4/5 outcomes. Methods: Adult pts with classical HL and PET2 findings of D3, D4, and D5 after initial therapy between 01/01/2015 and 07/01/2019 were identified. Pts enrolled in clinical studies were excluded. Retrospective demographic, clinical, and treatment data were obtained and described from 14 academic and community sites across North America (NA). Progression-free survival (PFS) and overall survival (OS) were summarized by Kaplan-Meier curves and compared by log-rank test. Results: 166 PET2 positive pts were identified. Clinical characteristics included 54% (89/166) with advanced stage (III/IV) and 46% (77/166) with early stage (IA-IIB) disease. 152 pts (92%) were treated with initial ABVD like therapy and 14 pts (8%) with an alternate regimen (Table 1). After initial treatment, 163 pts demonstrated PET2 scores of D3 (n=33), D4 (n=99) and D5 (n=31). Of the 130 D4/5 pts; 23% (30/130) underwent therapeutic escalation and 77% (100/130) did not escalate. The complete response rate (CR) at end of treatment (EOT) for all D4/5 patients receiving escalation was 37% (11/30) compared to 45% (45/100) without escalation (p=0.43). (Table 2) The 12 month PFS was 54% (38.2-76.3) versus (vs) 69.2% (60.4-79.2) for escalation and no escalation respectively. Of the 66 D4/5 pts with advanced stage disease; 21% (14/66) had therapeutic escalation and 79% (52/66) did not escalate. CR at EOT was noted in 29% (4/14) with escalation vs 31% (16/52) without escalation (p=0.88). (Table 2) The 12 month PFS was 54.2% (32.9-89.3) vs 57.5% (44.9-73.7) for escalation and no escalation respectively. (Figure 1; Log Rank p=0.38). Of the 64 D4/5 pts with early stage disease; 75% (48/64) did not undergo escalation and 25% (16/64) had escalation. CR at EOT was noted in 44% (7/16) with escalation vs 60% (29/48) without escalation (p=0.26). (Table 2) The 12 month PFS was 54.7% (34.5-86.7) vs 80.8% (70.2-92.9) for escalation and no escalation respectively. Of the 33 D3 pts; 52% (17/33) de-escalated with the remainder (16/33) continuing on initial therapy. No D3 pt underwent escalation. In the 12 D3 pts with early stage disease, 50% (6/12) de-escalated. Of the 21 D3 pts with advanced stage disease; 52% (11/21) had de-escalation and 48% (10/21) did not de-escalate. CR at EOT was noted in 71% (12/17) with de-escalation vs 81% (13/16) without de-escalation (p=0.50). (Table 2) Progression was noted in 29% (5/17) of patients who underwent de-escalation compared to 38% (6/16) without de-escalation. The 12 month PFS was 76.5% (85.8-99.6) vs 72.1% (52.2-99.7) for de-escalation and no de-escalation respectively. Conclusion: This is the first study evaluating clinical practice patterns and outcomes of PET adaptive therapy in NA. In this retrospective study, less than a quarter of advanced stage ABVD-treated D4/5 pts had therapy escalation despite prior studies reporting benefit. Our data suggest that outcomes for advanced stage PET positive pts are suboptimal irrespective of therapeutic escalation. In addition, pts with D3 findings represent a heterogeneous population and demonstrate favorable outcomes compared to D4/5 pts. Longer follow up time and further studies with larger numbers of pts are essential for confirming the reported findings. Disclosures Rutherford: Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; Juno Therapeutics Inc: Consultancy, Honoraria. Bartlett:ADC Therapeutics: Consultancy, Research Funding; Affimed: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Genenetech: Research Funding; Gilead: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Merck: Research Funding; Millenium: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding. Maddocks:Novartis: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; BMS: Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees. Feldman:Takeda: Honoraria, Speakers Bureau; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Portola Pharma: Research Funding; Pfizer: Research Funding; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Corvus: Research Funding; Roche: Research Funding; Cell Medica: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau. Magarelli:Tevan Oncology: Speakers Bureau. Advani:Merck: Research Funding; Infinity Pharma: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Millennium: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agensys: Research Funding; Seattle Genetics: Consultancy, Research Funding; Stanford University: Employment, Equity Ownership; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Regeneron: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cell Medica, Ltd: Consultancy; Forty-Seven: Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stephens:Karyopharm: Research Funding; Gilead: Research Funding; Acerta: Research Funding. Patel:Sunesis: Consultancy; Genentech: Consultancy, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Tees:Celgene: Speakers Bureau; Pharmacyclics: Speakers Bureau. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Cheson:Portola: Research Funding; Kite: Research Funding; Gilead: Research Funding; Symbios: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Trillium: Research Funding; Epizyme: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Yazdy:Bayer: Honoraria, Speakers Bureau; Octapharma: Consultancy; Genentech: Research Funding; Abbvie: Consultancy. Pagel:AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Ramchandren:Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Merck: Research Funding; Sandoz-Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an Abbvie company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.