ALBERT

Description: Introduction: Ibrutinib, an orally and continuously administered Bruton tyrosine kinase inhibitor, allows for targeted, non-chemotherapy based treatment for chronic lymphocytic leukemia (CLL). While the initial US marketing approval for ibrutinib in CLL was for relapsed disease (February 2014), several trials have since shown favorable efficacy in the first-line setting. Ibrutinib was well tolerated in these pivotal studies, with discontinuation occurring in less than 9% at 12 months (O'Brien et al., Am J Hemato. 2019). Most early ibrutinib discontinuations in the first-line setting are due to adverse events (Tedeschi et al., EHA 2019), and optimal strategies to manage ibrutinib-related toxicities are not well defined. We hypothesized that ibrutinib is increasingly utilized for first-line treatment of CLL during routine management in the US, but that ibrutinib discontinuation rates for the real-world population are greater than those reported in clinical trials. Further, we expected to find greater odds of discontinuation in older adults and those with poor performance status, two groups underrepresented in clinical trials. Methods: We conducted a retrospective cohort study of CLL patients treated at community oncology practices using the nationwide Flatiron Health database. The Flatiron Health database is a longitudinal, demographically and geographically diverse database derived from de-identified electronic health record data from over 280 cancer clinics in the US. All patients initiated CLL therapy in the first-line setting between March 1, 2014 and February 28, 2019. We first assessed trends in the use of first-line ibrutinib (i.e., ibrutinib with/without an anti-CD20 antibody). We then focused on patients who received ibrutinib and had at least 180 days of available follow up or had died within this period. We used multivariable logistic regression to assess the association of patient characteristics with early discontinuation (defined as stopping within 180 days of initiation). Covariates included in our model were patient age, sex, race, insurance type, ECOG performance status, year of treatment, time from CLL diagnosis to ibrutinib initiation, chromosome 17p status, and geographical region. Results: We identified 5,634 individuals initiating first-line treatment for CLL, of whom 1,639 (29.1%) received an ibrutinib-based regimen. Use of ibrutinib in the first-line setting increased over time (Cochrane-Armitage test for trend, p

Description: Background: Induction chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for transplant eligible (TE) patients (pts) with untreated mantle cell lymphoma (uMCL); however, there is no consensus on the optimal induction regimen. The addition of rituximab + high-dose cytarabine (RC) to an RCHOP-like regimen is associated with better outcomes. In addition, two randomized trials have demonstrated superior efficacy and tolerability for rituximab/bendamustine (RB) compared to RCHOP for uMCL. Based on this, we conducted a phase 2 trial of 3 cycles of RB followed by 3 cycles of RC in 23 TE pts with uMCL, with encouraging preliminary results (Armand, BJH 2016). Pts continued to be followed for relapse and survival. Meanwhile, RB/RC became the standard frontline regimen at Dana-Farber Cancer Institute (DFCI). Simultaneously, investigators at Washington University in St. Louis (WUSTL) initiated a similar study of alternating cycles of RB/RC for uMCL. Herein, we report the results of both phase 2 trials as well as the off-trial experience. Methods: In the DFCI trial, TE pts (age 18-69) with uMCL were treated with 3 cycles of RB (R 375 mg/m2 d1, B 90 mg/m2 d1-2) followed by 3 cycles of RC (R 375 mg/m2 d1, C 3gm/m2 BID d1-2 with dose reductions for age, renal dysfunction, or pre-existing neurotoxicity). Off-trial pts treated with RB/RC at DFCI or in consulting community practices were retrospectively identified using clinical and pharmacy databases. In the WUSTL trial, TE pts (age 18-65) received alternating cycles of RB (cycles 1, 3, 5) and RC (cycles 2, 4, 6) (same dosing as above). Response assessments were made using CT scans for the DFCI trial and PET/CT for the WUSTL trial and DFCI off-trial pts. Results: In total, 86 pts (23 DFCI trial, 49 DFCI off-trial, 14 WUSTL trial) were treated with RB/RC. The median age was 57 (range 30-72). Pts in the WUSTL cohort were more likely to be male, have a high MIPI score, and have blastoid variant (Table). 94% of pts completed 6 cycles of RB/RC therapy. Off-trial pts were more likely to receive a lower starting dose (≤ 2gm/m2) of cytarabine (76%) compared to trial pts (38%). At the EOI, the overall response rate and CRR were 98% and 92%, respectively, with similar response rates across cohorts (Table). 73 pts (85%) subsequently underwent ASCT and 4 additional pts (5%) have ASCTs planned. 9 pts did not undergo ASCT because of persistent or PD (n=3), prolonged cytopenias (n=3), an incidentally identified ASXL1 mutation without cytopenias (n=1), pt preference (n=1), and inadequate stem cell collection (n=1). Delayed platelet engraftment after ASCT was seen for pts receiving alternating cycles of RB/RC compared to sequential RB/RC at day 30 (plts

Description: INTRODUCTION: Timely goals of care (GOC) discussions improve end-of-life (EOL) care for patients with solid malignancies. Although timely GOC discussions might also improve EOL care for patients with blood cancers, data are sparse regarding such discussions for this population. We studied the impact of timing and location of GOC discussions on quality of EOL care for a cohort of patients who died of blood cancers. METHODS: We assembled a retrospective cohort of blood cancer decedents from Dana-Farber Cancer Institute, Boston, MA. We included patients diagnosed with a blood cancer, who had ≥ 2 outpatient visits at the study institution, and who died between January 1 and December 31, 2014. Using the established definition from Mack et al, JCO 2012, we classified patients as having had a GOC discussion if there was any documentation in the medical record of a discussion involving resuscitation status, hospice, or preferred location of death. We abstracted content and location of the first documented GOC discussion. Next, we ascertained intensity of care near the EOL (i.e. chemotherapy ≤ 14 days before death, intensive care unit [ICU] admission ≤ 30 days before death, and hospital death) and hospice enrollment. Of note, decreased intensity of medical care and high rates of hospice enrollment are accepted indicators of quality EOL care. In univariable and multivariable models, we assessed the potential relationship between timing (〉 or ≤ 30 days before death) and location (outpatient or inpatient) of GOC discussions with intensity of medical care and hospice use near the EOL. RESULTS: Of the 384 eligible deceased patients, 39.1% had leukemia/myelodysplastic syndromes, 37.2% had lymphoma, and 23.7% had myeloma. 40.6% had undergone a hematopoietic stem cell transplant (HCT). Overall, 235 (61.2%) had a documented GOC discussion. The median time between first documented discussion and death was 15 days, with 33.2% of first discussions occurring 〉 30 days before death, and the minority (36.2%) occurring in the outpatient setting. The most commonly discussed topic was resuscitation preferences (82.6%), followed by hospice (30.6%); preferred location of death was rarely discussed (3.4%). Of the entire cohort, 16.9% received chemotherapy ≤ 14 days before death, 21.6% had at least one ICU admission ≤ 30 days before death, and 38.0% died in the hospital. 49.5% of the study population experienced at least one indicator of high-intensity medical care near the EOL. The rate of hospice use was 24.2%. In univariable analyses among those who had EOL discussions (n=235), having the first GOC discussion 〉 30 days before death was significantly associated with a lower likelihood of ICU admission ≤ 30 days before death (14.1% vs. 40.8%, p

Description: Lymphomas represent nearly 70 distinct diseases with unique clinical presentations, therapeutic responses and underlying biology. There is a pressing shortage of publically available cell line and in vivo models of nearly all of these diseases, which has severely hampered efforts to understand and target their biology. To address this issue, we have established a repository of patient-derived xenografts (PDX) of lymphomas by engrafting human tumors into immunodeficient NOD/SCID/IL2rgnull (NSG) mice. These lymphomas, along with a spectrum of other PDXs of hematologic malignancies, are available to collaborators through the online portal PRoXe (Public Repository of Xenografts) at http://PRoXe.org. Blood and bone marrow specimens involved with tumor are injected by tail vein (IV) injection. Lymph node and extranodal biopsy specimens are implanted under the renal capsule as a 1x1x2mm tumor seed (renal), which maintains the in situ microarchitecture. A full description of xenografted lymphomas is included in the Table. Table 1.DiseaseType of implant# in 1st passage# in 2nd passage or higherT-cell prolymphocytic leukemiaIV1Angioimmunoblastic T-cell lymphomaIV11Mantle cell lymphomaIV12Double-hit DLBCLIV2Sézary SyndromeIV1Adult T-cell Leukemia/LymphomaIV1Diffuse large B cell lymphomaIV2Diffuse large B cell lymphomarenal2Marginal zone lymphomarenal11NK/T-cell lymphomarenal1Peripheral T-cell lymphoma-NOSrenal1Breast implant-associated anaplastic large cell lymphomarenal1 Engrafted PDXs have been extensively characterized by immunohistochemistry, flow cytometry, transcriptome sequencing and targeted DNA sequencing. Flow cytometric analysis of patient tumors and their respective xenografts consistently revealed highly concordant immunophenotypes compared to the original tumors. Similarly, immunohistochemistry of involved tissues confirmed retention of tumor immunophenotypes, architecture, and even tissue tropism in the PDXs. Examples include a Sézary syndrome PDX that was injected by tail vein and trafficked to spleen, bone marrow, blood and skin, a diffuse large B-cell lymphoma (DLBCL) PDX that infiltrated the CNS, and a second DLBCL PDX that was implanted into the renal capsule of the left kidney and progressed within 8 weeks to bilateral renal involvement. Other notable models include a breast implant-associated, ALK-negative anaplastic large cell lymphoma implanted under the renal capsule that metastasized to the liver and spleen while uniformly retaining CD30 positivity. Two double-hit lymphoma (DHL) PDXs maintained their CD20-negative phenotype through serial passage to P1. A peripheral T-cell lymphoma-NOS (PTCL) specimen implanted under the renal capsule engrafted in the spleen, with a notable admixture of nonmalignant T cells and scattered EBV-positive B cells. T-cell receptor gene rearrangement PCR performed on this PTCL demonstrated an identical rearrangement pattern in the primary tumor and the PDX. Luciferized mantle cell lymphoma and DHL PDXs clearly home to bone marrow, lymph nodes, spleen, and liver as early as two weeks after injection. These findings support the utility of these PDX lines as in vivo models that more accurately recapitulate the human disease than commonly used subcutaneous cell line models. In addition to generating PDXs that remain faithful to their source tumors, we have witnessed interesting examples of in vivo histologic transformation, opening the door to studies of disease progression. One primary follicular lymphoma specimen injected into a cohort of mice transformed to DLBCL in one mouse and a lymphoblastic lymphoma-like disease in another mouse, as confirmed by IHC and flow cytometry. Further xenografting of primary tumors is underway with the goal of establishing a large repository of lymphoma PDXs useful for biologic interrogation and preclinical trials. Disclosures Davids: Genentech: Other: ad board; Pharmacyclics: Consultancy; Janssen: Consultancy. Shipp:Gilead: Consultancy; Sanofi: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees.

Description: Background: Although there is an increasing focus on the provision of quality end of life (EOL) care for cancer patients, little is known about the factors that influence hospice use for patients with lymphoma. Utilization of palliative services is also felt to be lower in hematologic oncology. We aimed to characterize the prevalence and predictors of hospice enrollment in a large population of patients with B-cell non-Hodgkin lymphoma (NHL). Methods: We conducted a retrospective analysis using the Surveillance Epidemiology and End Results (SEER)-Medicare database. Patients ≥ 65 years of age who were diagnosed with any B-cell NHL, lived for at least 30 days, and died between January 1, 2000 and December 31, 2010 were eligible. We divided the cohort into three groups: those with indolent NHL (chronic lymphocytic leukemia and follicular, marginal zone, and lymphoplasmacytic lymphoma), aggressiveNHL (diffuse large B-cell, Burkitt, primary mediastinal B-cell, and primary effusion lymphoma), and mantle cell lymphoma (MCL). MCL was considered a unique group because, while it is largely incurable like indolent NHL, it often has a more aggressive clinical course. We first characterized the prevalence and covariates of hospice use in the cohort. Next, we fit a multivariable logistic regression model to characterize factors associated with hospice use, including NHL type (indolent, aggressive, MCL) and patient sociodemographic characteristics with p 〈 0.05 in univariable analyses. Results: A total of 18, 815 patients were eligible, of which 9,666 had indolent NHL, 8,241 had aggressive NHL, and 908 had MCL. Of the total cohort, 7,820 (42%) enrolled in hospice, with 6,450 (34% of the total cohort) enrolled ≥ 3 days before death. There were significant differences in hospice use by NHL type, with 39% of indolent NHL patients, 44% of aggressive NHL patients, and 48% of MCL patients enrolling in hospice respectively (p 〈 0.001). Multivariable associations of patient characteristics with hospice use are shown below. Figure 1 *Multivariable model adjusted for all covariates in table and time from diagnosis to death. The median time from diagnosis to death was significantly longer for patients who enrolled in hospice (37.5 months) compared with those who did not enroll (31.8 months, p 〈 0.001); effects were similar in analyses stratified by lymphoma type. Conclusions: In this large cohort of patients with B-cell NHL, the rate of hospice use ≥ 3 days before death (34%) was substantially lower than the 2007 national average of 43% for all cancer decedents (National Hospice and Palliative Care Organization Facts and Figures, 2012). This finding is provocative: it suggests either the need for improvements in enrollment and/or that our current hospice model is not meeting the specific needs of lymphoma patients in the United States. We also found disparities in hospice use similar to those previously observed in solid malignancies, with non-white patients and those of lower socioeconomic status less likely to enroll. Moreover, patients who enrolled were more likely to have lived longer after their diagnosis, perhaps due to increased experience withand thus desire to avoidthe burden of additional treatments. Finally, the fact that patients with MCL had the highest rate of enrollment may reflect its increased symptom burden, and often aggressive course in the context of being incurable. These may be clearer indicators of the EOL phase and the need for hospice. Disclosures No relevant conflicts of interest to declare.

Description: Background The two most commonly accepted approaches for limited stage, non-bulky diffuse large B-cell lymphoma (DLBCL)—an abbreviated course of chemoimmunotherapy (CIT) with radiation (RT) or an extended course of CIT alone—are largely based on studies performed prior to the widespread use of rituximab. Little is known about the comparative effectiveness of these treatment approaches, especially for the elderly. Methods We conducted a retrospective analysis using the Surveillance Epidemiology and End Results database linked to Medicare claims (SEER-Medicare). Patients 〉 65 years of age diagnosed with stage I or II DLBCL between January 1, 1999 and December 31, 2009 were eligible. Patients who received RT prior to CIT or 6 to 8 cycles of CIT plus RT were excluded, as we considered these to be surrogates for bulky disease. We characterized the prevalence and covariates of treatment types initiated within 180 days of diagnosis: standard treatment (3 to 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [RCHOP] plus RT or 6 to 8 cycles of RCHOP), nonstandard treatment (any therapy except standard treatment), and no treatment. We also characterized disability status, defined as “poor” if there were any claims for mobility aids, oxygen therapy supplies, home care services or skilled nursing facility admissions in the 12 months prior to diagnosis. Next, using propensity-score weighted Cox regression models that included available sociodemographic and clinical characteristics (see Table), we compared treatment-free (TFS) and overall survival (OS) for patients who received one of the two standard treatments. TFS was defined as freedom from one of two events: evidence of subsequent treatment (any new claim for chemotherapy occurring 〉 90 days after the completion of initial therapy) or death. We also assessed the odds of hospitalization and of developing poor disability status in the year following therapy for both standard treatments. Results A total of 4,035 patients were eligible: 24% received standard treatment, 66% received nonstandard treatment and 10% received no treatment. Among the patients with nonstandard treatment, 13% received RT alone, 26% received 〈 6 cycles of RCHOP and no RT, 9% received 1, 2 or 5 cycles of RCHOP plus RT, and 52% received therapy other than RCHOP. Of those who received standard treatment, 439 received 3 to 4 cycles of RCHOP plus RT and 530 received 6 to 8 cycles of RCHOP. Characteristics of the standard treatment groups are shown below (see Table). In the propensity score analysis, TFS and OS for patients who received abbreviated CIT plus RT compared to an extended course of CIT alone were not significantly different (see Figure 1; propensity score adjusted hazard ratio [HR] for TFS 0.90, 95% CI [0.72, 1.12], p = 0.33; HR for OS 1.18, 95% CI [0.92, 1.53], p = 0.19). In addition, the odds of hospitalization was not different for patients who received abbreviated CIT plus RT compared to extended CIT (OR 0.90, 95% CI [0.70, 1.16], p = 0.43) and neither were the odds of developing poor disability status (OR 1.37, 95% CI [0.97, 1.94], p = 0.10). Conclusion In this large cohort of elderly patients with a potentially curable disease, a significant proportion received non-standard therapy or no treatment at all. For those able to complete standard treatment, there was no difference in TFS or OS comparing 3 to 4 cycles of RCHOP plus RT with 6 to 8 cycles of RCHOP, confirming clinical trial findings from the pre-rituximab era. Moreover, the lack of differences in subsequent hospitalizations or changes in disability status suggests similar tolerability, and thus similar effectiveness of both treatments. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Hematologic malignancies have been associated with poor performance on standard measures of quality of end-of-life (EOL) care in oncology (eg, Hui, Cancer, 2014); however, these measures were originally developed primarily for solid tumors, and they may not appropriately address EOL quality issues for patients with blood cancers. We sought to explore hematologic oncologists' perspectives regarding the acceptability of current oncology EOL quality measures, hypothesizing that they would report them to be largely unacceptable. Methods: In 2014, we mailed a 30-item survey to a national sample of hematologic oncologists randomly selected from the American Society of Hematology clinical directory. The survey was developed through focus groups (n=20) and cognitive debriefing (n=5) with hematologists whose practices focus on patients with blood cancers. In the resulting survey, we provided a list of standard EOL quality measures (Earle, JCO, 2003; Keating, Cancer, 2010; Phelps, JAMA, 2009; see table) and two novel hematology-based measures (no red cell transfusions ≤ 7 days before death, and no platelet transfusions ≤ 7 days before death) and asked "Please indicate whether or not you feel each is an acceptable indicator of good quality EOL care for patients with hematologic malignancies." We decided a priori that we would consider a measure to be "highly acceptable" if there were at least 75% agreement among hematologic oncologists on its acceptability. Worrying that they might reject them all, we also asked them to identify three measures they would choose in a scenario where three had to be adopted. Results: We received 349 surveys from 48 states (response rate: 57.3%). Non-responders were not significantly different across known variables (gender and region of practice). Among respondents, median age was 52 years, median time in practice was 25 years, and 43% practiced primarily in tertiary centers. Eighty-seven percent were board-certified in oncology, 81% in hematology, and 71% in both specialties. The table below shows acceptability of the quality measures as rated by respondents. In the exercise where three measures had to be chosen, the one chosen most often was no CPR within 30 days of death (54%), followed by enrollment in hospice 〉7 days before death (46%). Conclusions: In contrast to our hypothesis, all of the measures we presented were considered acceptable by a substantial proportion of the hematologic oncologists in our national cohort. Moreover, while four of the measures reached our a priori designation of being highly acceptable, the two hematology-focused measures did not meet this same threshold. These data suggest that in hematologic oncology, resources should be directed towards addressing barriers to performance on established EOL quality measures in addition to creating new ones. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.

Description: Background: End-of-life (EOL) care has been shown to be more intensive for blood cancers compared to solid tumors (e.g. Hui, Cancer, 2014); however, data are sparse regarding predictors of intensive care unit (ICU) use in the last 30 days of life and hospice enrollment among patients with specific hematologic malignancies. Moreover, little is known about EOL care specifically for the myelodysplastic syndromes (MDS), which are distinguished among the blood cancers by their relative indolence in many patients and high rate of transfusion dependence. Methods: We conducted a retrospective analysis using the Surveillance Epidemiology and End Results (SEER)-Medicare database. Patients ≥ 65 years of age who had a primary diagnosis of MDS between 2006 and 2011, lived for at least 30 days after their diagnosis, and died prior to December 31, 2012 were eligible for inclusion. Outcomes were two well-established quality measures for EOL care in oncology (Earle, JCO, 2003; Keating, Cancer, 2010): ICU admission within the last 30 days of life (an indicator of poor quality), and enrollment in hospice for any length of time (an indicator of good quality). After determining their overall prevalence, we fit multivariable logistic regression models to investigate sociodemographic and clinical associations (see table) with each outcome. Results: A total of 6,955 MDS patients were eligible. Overall, 28% were admitted to the ICU in the last month of life, and 49% had enrolled in hospice. In multivariable analyses, transfusion-dependent patients were more likely to be admitted to the ICU and less likely to enroll in hospice (both p

Description: Background: Classical Hodgkin lymphoma (cHL) displays near-universal genetic deregulation of PD-1 ligand expression, and relapsed/refractory (R/R) cHL is uniquely sensitive to PD-1 blockade. However, such treatment for patients (pts) who relapse after or are ineligible for autologous stem cell transplantation (ASCT) appears to be rarely, if ever, curative. Deploying PD-1 blockade early after ASCT could leverage the remodeling immune landscape and minimal residual disease state to increase the cure rate of ASCT. We therefore conducted a phase 2 multi-center single-arm study of the anti-PD-1 monoclonal antibody pembrolizumab (pembro) in pts with chemosensitive R/R cHL after ASCT. Another arm of this study enrolled pts with R/R DLBCL and will be presented separately. Methods: Adult pts with R/R cHL who had received 2-3 lines of prior therapy and ASCT and who were chemosensitive prior to ASCT were enrolled on this study. In addition to meeting standard eligibility criteria for pembro treatment, pts had to have recovered from ASCT toxicities and begin study treatment within 60 days of stem cell infusion (goal within 21 days). They received pembro 200mg IV every 3 weeks for 8 cycles. PET-CT scans were obtained at post-ASCT baseline, after 3 and 7 cycles, then at 12 and 18 months post-ASCT. The primary endpoint was the progression-free survival rate (PFS) at 18 months after ASCT, assessed using International Harmonization Project 2007 criteria. Results: 31 pts were enrolled and 1 withdrew consent before starting treatment. Among the 30 eligible patients, median age was 33 (20-69). 26 pts (87%) were high-risk by virtue of primary refractory disease (57%), relapse within 12 months (17%), extranodal disease at relapse (27%) or absence of metabolic CR at ASCT (10%). At study baseline post-ASCT, 97% were in CR. 24 pts (80%) completed 8 cycles of pembro per protocol. 6 pts (20%) stopped pembro early for pt choice (n=2, including 1 pt with gr2 pneumonitis) or toxicity (n=4, including 2 pts with gr3 hepatitis, 1 with g3 pneumonitis, 1 with g2 diplopia). 9 pts (30%) experienced a total of 28 gr3 or higher adverse events (AEs). The most common gr4 AE was neutropenia (10%). 3 patients (10%) experienced 7 gr3-4 AEs at least probably related to pembro (gr3 diarrhea and gr3 eosinophilic colitis in 1 pt, gr3 leukopenia and gr4 neutropenia in 1 pt, gr3 leukopenia and gr3 ALT and AST elevation in 1 pt). 11 pts (37%) experienced at least one immune-related AE of gr2 or higher severity: pneumonitis (n=2 gr2, n=1 gr3), thyroid dysfunction (n=1 gr2), transaminitis (n=2 gr3), colitis/diarrhea (n=1 gr2, n=2 gr3), rash (n=2 gr2), pulmonary hemorrhage (n=1 gr3), arthritis (n=1 gr2), and increased creatinine (n=1 gr2). There was no treatment-related death. Among the 30 eligible pts, 2 were lost to follow-up after their 12m assessments (both in CR). 27 pts (90%) were evaluable for the primary endpoint (the last pt is still in follow-up and results will be updated for the meeting). 6 patients (20%) relapsed at a median of 8 months (3-18) from ASCT, and all other evaluable patients were in CR at the 18m timepoint. The KM estimate of 18m PFS for high-risk patients was 78% (95%CI 54-91). The 18m overall survival was 100%. Tumor biopsies from a pt who progressed on study demonstrated an increase in the %age of PD1+ T cells at progression, as well as an increase in the %age of PD-L1+ macrophages and PD-L1+ Reed-Sternberg cells (Figure). Other correlative studies including immune reconstitution and MRD analyses are ongoing. Conclusions: Pembrolizumab administered after ASCT in patients with R/R cHL has a safety profile that appears similar to its use in the R/R setting, although possibly with a higher rate of neutropenia. The 18-month progression-free rate in this high-risk cohort compares favorably with previous published studies, and supports the hypothesis that PD-1 blockade in this setting may increase the efficacy of ASCT. This should be tested in a randomized trial. Figure. Figure. Disclosures Armand: Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy; Adaptive: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Chen:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Consultancy; Magenta Therapeutics: Consultancy; REGiMMUNE: Consultancy. LaCasce:Humanigen: Consultancy, Honoraria; Research to Practice: Speakers Bureau; Bristol-Myers Squibb: Other: Data safety and monitoring board; Seattle Genetics: Consultancy, Honoraria. Jacobson:Pfizer: Consultancy; Humanigen: Consultancy; Precision Bioscience: Consultancy; Novartis: Consultancy; Kite: Consultancy; Bayer: Consultancy. Jacobsen:Merck: Consultancy; Seattle Genetics: Consultancy. Rodig:Bristol-Meyers-Squibb: Research Funding; KITE Pharma: Research Funding; Affimed Inc.: Research Funding; Merck & Co., Inc.: Research Funding. Shipp:AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Merck: Research Funding. Herrera:BMS: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; KiTE Pharma: Consultancy, Research Funding; Seattle Genetics: Research Funding; Immune Design: Research Funding; Astra Zeneca: Research Funding.