ALBERT

Description: Introduction Classic Hodgkin's lymphoma (cHL) is a highly curable lymphoid malignancy. Most of the patients receive either bleomycin or brentuximab vedotin (BV) based therapies as a frontline treatment. Treatment alterations are common and can be related to toxicity, patient's preference, and/or clinical evidence of response. The aim of our study is to explore the frequency and characteristics of treatment alterations, especially bleomycin and BV, in frontline therapies used in newly diagnosed cHL. Methods This single center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Patients' charts were reviewed to assess frequency of treatment discontinuation at the time of frontline therapy and underlying reasons for any treatment alterations. The primary aims were to assess the frequency of treatment alterations and its effects on overall survival (OS), and progression-free survival (PFS). Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and lab measurements, and frequency counts and percentages for categorical variables such as race, gender, and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results In the studied period, 644 patients met the inclusion criteria. The median age at diagnosis was 33 years (range:9-85) with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients. Ninety-seven percent of patients had 0-1 Eastern Cooperative Oncology Group (ECOG) performance status. Histological subtype was predominately nodular sclerosis (83%). International prognostic index at the time of diagnosis was ≥4 in 13% of patients. Most of the patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%). Other therapies included brentuximab vedotin (BV)(13%) and checkpoint inhibitors (CPIs) (6%, as a part of clinical trial). Patient's demographics are outlined in Table.1. Treatment alteration, which included either addition or omission of drug/s, occurred in 26% of patients. The most common discontinued drugs were bleomycin (79%), and BV (15%). Of the patients who were started on ABVD based therapy, the frequency of bleomycin discontinuation was 26% (116 of 455 patients). The most common reasons for bleomycin discontinuation were: treatment response as per the RATHL study (49%), pulmonary toxicity (27%) and other treatment-related toxicity (9%). Of the patients who were started on frontline BV based therapy, the frequency of BV discontinuation was 26% (20 of 78 patients). The most common reasons for BV discontinuation were: peripheral neuropathy (65%), skin rash (10%) and other treatment-related toxicity (25%). Patients who discontinued bleomycin due to adverse events (AEs) had a higher chance of primary refractory disease at the end of frontline treatment (19% vs. 15%, p-value: 0.005) while patients who discontinued bleomycin due to treatment response had similar rates of primary refractory disease (13% vs. 15%, p-value: 0.57). The median cycles number of bleomycin based therapy were the same (6 cycles) among all the groups (those who continued bleomycin without AEs or discontinuation, patients who discontinued bleomycin for treatment response and patients who discontinued bleomycin for AEs) . Patients who discontinued BV due to AEs had similar outcome to the patients who continued the treatment without alterations. Conclusions Frontline treatment alterations in cHL are common. Positron emission tomography treatment response based bleomycin discontinuation was not associated with worse PFS or OS. However bleomycin discontinuation secondary to AEs was associated with a statistically significant higher rate of primary refractory disease and subsequent worse PFS and OS. BV discontinuation secondary to AEs didn't result in worse outcomes. Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Iyer:CRISPR:Research Funding;Spectrum:Research Funding;Merck:Research Funding;Afffimed:Research Funding;Rhizen:Research Funding;Seattle Genetics, Inc.:Research Funding;Legend Biotech:Consultancy;Daiichi Sankyo:Consultancy;Trillium:Research Funding;Curio Biosciences:Honoraria;Target Oncology:Honoraria.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Secura Bio:Other: Grant Support;Astra Zeneca:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Pulse Biosciences:Consultancy;Molecular Templates:Research Funding;BioInvent:Research Funding;VelosBio:Research Funding;Beijing Medical Award Foundation:Honoraria;Juno:Consultancy, Research Funding;Oncternal:Consultancy, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;InnoCare:Consultancy;Loxo Oncology:Consultancy, Research Funding;Verastem:Research Funding;Acerta Pharma:Research Funding;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;OncLive:Honoraria;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Nobel Insights:Consultancy;Guidepoint Global:Consultancy;Dava Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Targeted Oncology:Honoraria.Lee:Celgene:Research Funding;Guidepoint Blogal:Consultancy;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau;Oncternal Therapeutics:Research Funding;Seattle Genetics:Research Funding;Takeda:Research Funding.

Description: Introduction Vitamin D deficiency is a modifiable risk factor for multiple malignancies. There is growing evidence that associates vitamin D deficiency with progression-free survival (PFS) and overall survival (OS) in patients with classic Hodgkin lymphoma (cHL). Supplemental ergocalciferol/cholecalciferol may improve chemosensitivity of malignant cells to chemotherapy as evidenced by reduction in the rate of tumor growth in a cHL- xenograft animal model. The goal of our study is to explore the association of pretreatment vitamin D levels on survival outcomes of patients with cHL. Methods We retrospectively reviewed the records of patients who were first seen at The University of Texas MD Anderson Cancer Center between January, 2016 and May, 2020 for newly diagnosed cHL. Patient charts were reviewed to assess demographic information, clinical staging at the time of vitamin D assessment, pretreatment 25-hydroxyvitamin D (25(OH) D) level and vitamin D supplementation. Vitamin D deficiency was defined as a 25(OH)D level 〈 30 nmol/L. PFS and OS outcomes were evaluated for these patients. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and 25(OH) D level, and frequency counts and percentages for categorical variables such as race, gender, vitamin D supplementation and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results 644 patients met the inclusion criteria of which 483 patients had their vitamin D levels assessed at the time of initial visit to this center. The median patient age at diagnosis was 33 years with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients of which the International Prognostic Score was ≥4 in 13% of patients. Patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%) and other agentss (6%). Patient demographics are outlined in Table.1. Pretreatment 25(OH)D level was assessed in 75% of the patients. The median 25(OH)D level was 25 nmol/L (range: 2-78 nmol/L). Vitamin D deficiency was present in 320 of 483 (66%) patients. Ergocalciferol/cholecalciferol supplementation was used in 29% of patients. There was no statistically significant association of vitamin D deficiency with advanced stage (p-value: 0.64). PFS rate at 10 years was significantly longer in patients with normal 25(OH)D level (40% vs 27%, p-value: 0.0481). Ergocalciferol/cholecalciferol supplementation was associated with a 6% improvement of PFS, however this difference was not statistically significant. No OS difference was noted between vitamin D deficient and non-deficient patients, an observation that persisted in patients on vitamin D supplementation versus not on supplementation. Conclusions Vitamin D deficiency was associated with inferior PFS with a 13% difference in vitamin D deficient versus non-deficient patients. There was a numerical PFS benefit associated with ergocalciferol/cholecalciferol supplementation. An OS benefit was not observed as the duration of follow up may not have been sufficient to observe the differential impact of vitamin D levels. Vitamin D screening and replacement is done in patients with newly diagnosed cHL and should be encouraged given the potential benefit from such approach. Prospective studies are warranted to establish the relationship between vitamin D level, supplementation and outcomes in cHL patients. Figure Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Beijing Medical Award Foundation:Honoraria;OncLive:Honoraria;Molecular Templates:Research Funding;Verastem:Research Funding;Dava Oncology:Honoraria;Guidepoint Global:Consultancy;Nobel Insights:Consultancy;Oncternal:Consultancy, Research Funding;InnoCare:Consultancy;Acerta Pharma:Research Funding;VelosBio:Research Funding;BioInvent:Research Funding;Juno:Consultancy, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;Loxo Oncology:Consultancy, Research Funding;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding.Lee:Takeda:Research Funding;Seattle Genetics:Research Funding;Oncternal Therapeutics:Research Funding;Guidepoint Blogal:Consultancy;Celgene:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau.

Description: BACKGROUND: Classic Hodgkin lymphoma (cHL) Nodular Sclerosis (NS) is the most common subtype of cHL and has a good prognosis. However, an uncommon variant of cHL NS, the syncytial variant (cHL NS-SV), represents an entity with a worse clinical outcome with conventional frontline cytotoxic therapy. Nevertheless, in the pivotal phase III study ECHELON-1, Brentuximab Vedotin (BV), doxorubicin, vinblastine, and dacarbazine (BV+AVD) while demonstrating a superior efficacy, unfortunately more febrile neutropenia (FN) and peripheral neuropathy (PN) were observed compared to bleomycin+AVD (ABVD) as frontline treatment of advanced-stage classical Hodgkin's lymphoma (cHL) (Straus et al Blood 2020). It is unknown whether BV combined with chemotherapy would improve the inferior prognosis of cHL NS-SV. METHODS: After obtaining institutional research approval, we retrospectively reviewed the characteristics and outcomes of adult cHL NS-SV patients, treated per physician preference with frontline BV combined with cytotoxic therapy, either as standard of care (SOC) or in a clinical trial (NCT01712490, NCT03646123 and NCT01060904) between 7/2010 and 7/2020. cHL NS-SV diagnosis was based on morphology and Immunophenotype. Bulky disease was defined as mass〉10cm or mediastinal mass 〉1/3 of thoracic diameter at T5-T6. Lymph node regions were defined by the German Hodgkin Study Group (GHSG). Treatment consisted of 0.9 or 1.2 mg/kg of BV and standard dose ABVD or AVD or D, intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. All patients received support with pegfilgrastim. Response assessment was based on positron emission tomography/computerized tomography (PET/CT). Follow-up time was calculated from the date of pre-treatment baseline lab measurement to relapse date or death date, whichever happened first. Patients with no event were censored at the last follow-up date. RESULTS: Among the 11 patients included in the analysis, the median age was 29 (range 19-59 years), 27.2% were female, and 90.9% were Caucasian. All patients had Eastern Cooperative Oncology Group (ECOG) 0-1, 72.7% of patients had B-symptoms and 81.9% had stage III or IV disease. The median size of the largest lesion was 9.0 cm, 45.5% of patients had bulky disease, 63.6% had extranodal disease, 72.7% had 〉3 GHSG involved nodal sites and median International Prognostic Score was 4. Overall, all patients received 6 cycles of therapy, 63.6% received BV+AVD, 27.3% received BV+ABVD and 1 patient received SOC BV with dacarbazine because of previous anthracycline exposure. The interim PET/CT showed response in all patients with Deauville score (DS) of 2-3 in 45.5% and 4 in 54.4%. The end-of-therapy PET/CT showed DS of 1-3 in 90.1% and 4 in 8.9%. The latter patient had the most voluminous bulk of this study. To date, no patient received additional systemic therapy or consolidative radiotherapy after completion induction therapy. With a median follow-up time of 14 months (range 5-82 months), no patient had relapse and all were still alive (Progression-Free Survival and Overall Survival of 100%). CONCLUSIONS: BV combined with cytotoxic therapy such as BV+AVD is a highly effective treatment strategy for patients with cHL NS-SV. Further studies are required to evaluate whether frontline therapy of BV+AVD could improve the outcome of the higher-risk subgroup cHL NS-SV. Table Disclosures Lee: Oncternal Therapeutics:Research Funding;Guidepoint Blogal:Consultancy;Aptitude Health:Speakers Bureau;Takeda:Research Funding;Seattle Genetics:Research Funding;Celgene:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding.

Description: Introduction The pathogenesis of classic Hodgkin's lymphoma (cHL) is largely unsettled. Previous studies have provided limited support to the possible association between tobacco smoking and outcome in cHL with inadequate evidence of a dose-outcome relationship. Smoking can result in a multitude of preventable malignancies, thus we studied the association between smoking, the initial stage of cHL and survival outcomes. Methods This single-center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Patients' charts were reviewed to assess the history of active smoking, former smoking and the amount of smoking (measured as pack-year). Former smoking was defined as history of smoking prior to the diagnosis of cHL and no active smoking at the time of diagnosis. The primary aims were to assess overall survival (OS), progression-free survival (PFS) and frequency of advanced disease at the time of diagnosis. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, amount of smoking and lab measurements, and frequency counts and percentages for categorical variables such as race, gender, history of current/prior smoking and response were analyzed. Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results Between 2016 and 2020, 644 patients met the inclusion criteria. The median age at diagnosis was 33 years (range: 9-85 years) with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients. Ninety-seven percent of patients had 0-1 Eastern Cooperative Oncology Group (ECOG) performance status. Histological subtype was predominately nodular sclerosis (83%). International Prognostic Index was =〉4 in 13% of patients. Most of the patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%)and checkpoint inhibitors (CPIs) based therapy (6%). Patient's demographics are outlined in Table.1. The percentage of active smoking was low at 6% (median age of active smokers: 33.5). History of prior smoking occurred in 21% of patients. The mean amount of smoking was 1.87 pack-year (rang :0. 05-54 pack-year). Active smoking was associated with advanced stage (9.5% vs. 4.9%, p-value: 0.033). PFS rate at 5 years was similar in smokers and non smokers (52% vs. 54%, p-value 0.9). OS rate at 10 years was better in never smokers when compared to former smokers (95% vs. 77%, p-value: 0.017). Univariable Cox proportional hazards model for OS showed a significant association between amount of smoking and OS with hazard ratio of 1.04 (95% CI: 1.005 1.07, p-value: 0.025). Conclusions We report the largest analysis of smoking status and impact on advanced stage and cHL clinical outcomes. Smoking history is associated with inferior 10 year OS (18% lower OS in patients with history of former smoking). Active smoking was associated with advanced stage however the frequency of active smoking in our patient database was low at 6% compared to previous reports of higher incidence of up to 20%. Patients should be counseled against smoking to avoid worse outcome associated with smoking in many clinical conditions including cHL. Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Iyer:Legend Biotech:Consultancy;CRISPR:Research Funding;Rhizen:Research Funding;Curio Biosciences:Honoraria;Target Oncology:Honoraria;Afffimed:Research Funding;Merck:Research Funding;Spectrum:Research Funding;Trillium:Research Funding;Daiichi Sankyo:Consultancy;Seattle Genetics, Inc.:Research Funding.Nieto:Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support;Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Guidepoint Global:Consultancy;Dava Oncology:Honoraria;Loxo Oncology:Consultancy, Research Funding;Verastem:Research Funding;Beijing Medical Award Foundation:Honoraria;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;OncLive:Honoraria;Molecular Templates:Research Funding;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;MoreHealth:Consultancy;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;BioInvent:Research Funding;Lu Daopei Medical Group:Honoraria;Juno:Consultancy, Research Funding;VelosBio:Research Funding;Acerta Pharma:Research Funding;InnoCare:Consultancy;Oncternal:Consultancy, Research Funding;Nobel Insights:Consultancy.Lee:Celgene:Research Funding;Seattle Genetics:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau;Guidepoint Blogal:Consultancy;Takeda:Research Funding;Oncternal Therapeutics:Research Funding.

Description: Introduction Classic Hodgkin's lymphoma (cHL) is a highly curable lymphoid malignancy. Epstein-Barr virus (EBV) is associated with cHL, with a variable rate of detection in Hodgkin and Reed-Sternberg (HRS) cells among different histologic types and geographic areas.Although most adults worldwide are EBV seropositive, only a minority of patients infected with EBV will develop cHL. EBV is thought to be one of the causative agents for the development of cHL with an important pathobiology role. The goal of this study was to compare the presentation and the outcomes of patients with EBV+ HRS cells at the time of initial diagnosis of cHL. Methods This single-center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Pathology was confirmed and analyzed for positivity of EBV (EBV +ve) in all patients by immunohistochemical (IHC) staining for by Epstein-Barr virus-encoded small RNA (EBER) with available paraffin blocks. The primary aims were to assess overall survival (OS), progression-free survival (PFS) and frequency of advanced disease. Descriptive statistics for categorical and continues variables were analyzed. Kaplan-Meier method was used for time-to-event analysis, including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results Between 2016 and 2020, 644 patients met the inclusion criteria. Three hundred and fifty six patients (55%) had enough/available tissue to undergo testing for EBV at the time of initial diagnosis. The median age at diagnosis was 36 years with 51.4% males. Eighty-eight patients had positive EBV (25%) at diagnosis. The median age of +ve EBV was 37 years (Range: 18-83 years) compared to 33 years (Range: 18-85 years) for patients with -ve EBV. Mixed cellularity histology was more frequent in patients with +ve EBV when compared to the whole group of patients (32% vs. 7%; p-value: 0.03). Human immunodeficiency virus (HIV) was positive in a minority of the patients (8 patients out of 498 patients with available results) (1.6%) however 50% of the patients with HIV had +ve EBV at the time of diagnosis. Baseline demographics are summarized in Table 1. EBV was associated with the initial stage (stage II 38% in EBV +ve vs. 53% in EBV -ve, stage III 25% in EBV +ve vs. 14% in EBV -ve, stage IV 24% in EBV +ve vs. 31% in EBV -ve; p-value 0.0001). Most of the patients were treated with doxorubicin, bleomycin, vinblastine and decarbazine (ABVD) based therapy (77%). Other therapies included brentuximab vedotin (BV) (13%) and checkpoint inhibitors (CPIs) (6%). Median follow up was 1.97 years (range: 0.047- 44.09 years). PFS rate difference at 5 years was not statistically significant (64% in EBV +ve vs. 52% in EBV -ve; p-value 0.14). OS rate at 5 years was significantly lower in patients with +ve EBV (89% vs. 98%, p-value: 0.0014). OS rates at 10 years were similar (89% in EBV +ve vs. 88% in EBV -ve). Conclusions EBV at the time of diagnosis was associated with lower prevalence of localized cHL and inferior survival rates at 5 years of follow up (9% lower OS rate at 5 years). Implementation of different frontline therapy treatment algorithms specific to EBV +ve patients may help in improving the survival outcomes. Further research is needed to understand the biological significance of +ve EBV in cHL to help in developing novel agents targeting EBV positive cHL population with the ultimate goal of improving outcome. Disclosures Parmar: Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Iyer:Rhizen: Research Funding; CRISPR: Research Funding; Seattle Genetics, Inc.: Research Funding; Merck: Research Funding; Legend Biotech: Consultancy; Daiichi Sankyo: Consultancy; Trillium: Research Funding; Curio Biosciences: Honoraria; Target Oncology: Honoraria; Afffimed: Research Funding; Spectrum: Research Funding. Nieto:Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support. Chuang:Sage-Evidence=Based Medicine & Practice: Consultancy. Wang:Beijing Medical Award Foundation: Honoraria; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Nobel Insights: Consultancy; Verastem: Research Funding; Dava Oncology: Honoraria; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Molecular Templates: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Targeted Oncology: Honoraria; Lu Daopei Medical Group: Honoraria; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Juno: Consultancy, Research Funding; OncLive: Honoraria; Guidepoint Global: Consultancy. Lee:Celgene: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau; Seattle Genetics: Research Funding; Oncternal Therapeutics: Research Funding; Guidepoint Blogal: Consultancy.

Description: HDC/ASCT is standard treatment of chemosensitive relapsed HL, with worse results for high-risk relapses (HRR) than for low-risk relapses. Aiming to improve the results of BEAM, we have studied newer HDC regimens seeking synergistic inhibition of DNA damage repair: gemcitabine/busulfan/melphalan (GBM) (Nieto, 2012) and vorinostat + GBM (SAHA/GBM) (Nieto, 2015). We wished to describe the evolution of results in HRR HL over the last 15 years and identify prognostic features. Methods We retrospectively analyzed all pts with HRR HL treated at MDACC with HDC/ASCT between 1/1/2005-12/31/2019. HRR HL was defined by ≥1 of the modified AETHERA criteria: primary refractory disease, relapse within 1 year of completing initial therapy, extranodal extension at relapse, B symptoms at relapse, or requiring 〉 1 salvage therapy line. All pts underwent similar pre-SCT evaluation and met eligibility criteria as per our institutional guidelines. HDC regimens included BEAM, busulfan/melphalan (BuMel), GBM and SAHA/GBM. Post-ASCT consolidative radiotherapy (RT) was considered for bulky relapses and/or PET+ lesions at ASCT. We evaluated age, gender, ASCT year, primary refractory disease, prior disease-free interval (DFI), prior radiotherapy (RT), relapse within prior RT field, extranodal extension at relapse, B symptoms at relapse, bulky relapse (largest lesion 〉5 cm), No. prior relapses, No. prior lines of therapy, prior brentuximab vedotin (BV), prior anti-PD1, PET results at ASCT, post-ASCT maintenance BV and post-ASCT RT. Differences by regimen cohort were tested with Kruskal Wallis or chi-square tests. Outcomes were compared with the log-rank test. Univariable and multivariable Cox regression analyses evaluated factors associated with progression-free survival (PFS) and overall survival (OS). Results A total of 501 pts, treated with BEAM (N=146), BuMel (N=38), GBM (N=189) and SAHA/GBM (N=128), were analyzed (Table 1). The GBM and SAHA/GBM cohorts had significantly more high-risk criteria (P=0.0006), with more pts with primary refractory disease (P=0.001) and bulky relapse (P