Citations

This report presents the American Society of Clinical Oncology’s (ASCO’s) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.

AbstractBackgroundA reliable history is critical to establish accurate clinical diagnoses, prioritize investigations and select appropriate treatments; yet few studies have considered the factors that influence the reliability of medical histories. Recognizing this, we determined the accuracy of medical history in community‐dwelling older adults engaged in longitudinal studies of memory and aging.MethodThe association between participant‐specific factors and accurate reporting of stroke or diabetes were evaluated using multivariable logistic regression in 1,401 participants enrolled in studies at the Knight Alzheimer Disease Research Center (Saint Louis, Missouri), including 425 participants with dementia (30.3%). History was verified with a reliable collateral source in all participants. Stroke and diabetes were selected as index variables, as gold standard measures—brain MRI for stroke and hemoglobinA1c (HbA1c) for diabetes—were routinely obtained in participants.Result25/862 (2.9%) participants endorsed a history of stroke, which was confirmed on MRI in 8/25 (positive predictive value, 17.4%). Stroke was detected on MRI in 38/837 (4.5%) of those without reported stroke (negative predictive value, 95.5%). Older age (OR per decade=1.7, 95%CI: 1.2‐2.5) and use of an unrelated collateral source (OR=2.0, 95%CI: 1.03‐3.7) were associated with greater odds of inaccurate reporting of stroke history. 190/1322 (14.4%) participants reported a history of diabetes, which was confirmed with HbA1c in 105/190 (positive predictive value, 55.3%). HbA1c 6.5% was detected in 29/1132 (2.6%) of those who denied diabetes (negative predictive value, 97.4%). African Americans (OR=1.6, 95%CI: 1.02‐2.6) and those with hypertension (OR=2.6, 95%CI: 1.5‐4.2) or HbA1c compatible with impaired glucose tolerance (OR=4.2, 95%CI: 2.7‐6.4) had greater odds of reporting a history of diabetes. Cognitive impairment was not associated with inaccurate reporting of stroke or diabetes.ConclusionThe accuracy of reported history of diabetes and stroke was low in older community‐dwelling participants, independent of cognitive status. A history of diabetes or stroke should be objectively confirmed when relevant to decision making in clinical and research settings.

Germ line mutations in H3F3A and H3F3B cause a previously unidentified neurodevelopmental syndrome.

Abstract Background Dyspnea on exertion (DOE) is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations (Effort/work of breathing, Chest tightness, Air hunger) that vary in intensity elicited by physical activity. Although DOE is a common presenting symptom in patients pertaining to cardiovascular and respiratory disorders, its prognostic importance in patients with no prior cardiovascular (CV) or respiratory disorders is unclear. Purpose The purpose of this study is to determine the prognostic significance of dyspnea on exertion (DOE) in patients with no prior diagnosis of CV or respiratory disorders. Methods We reviewed the Mayo Integrated Stress Center database for the period September 1993 through November 2010. Residents of Minnesota with no known heart disorders and no known history of COPD or other respiratory disorders were included in the study. Patients with abnormal ECG findings were excluded to rule out possible undiagnosed CV disorders. Limiting symptoms of DOE with reduced exercise capacity (FAC<90%). Our primary outcome was mortality which was adjusted for age, sex, smoking history, diabetes, hypertension, obesity, negative chronotropic medications. Statistical analysis was performed to evaluate hazard ratio using Cox regression models in SAS Studio. Results A total of 101,455 exercise tests were reviewed to identify 18960 patients (female = 6755, 35.6%) who met the study criteria. Mean age at the time of referral was 51.2±10 years (mean ± SD) and mean follow-up was 12±10 years (mean ± SD). There were 1331 (7%) deaths from all causes, out of which 368 (27.6%) deaths are from DOE patients, and there were 428 (2.2%) deaths from cardiac causes, out of which 141 (32.9%) deaths are from DOE patients. We found that DOE was an independent predictor of mortality from all causes with hazard ratio [95% CI] = 1.690 [1.488–1.918], p≤0.0001, and from cardiac causes with hazard ratio [95% CI] = 1.997 [1.613–2.473], p≤0.0001. Product-limit survival estimates of patients with and without DOE are shown in Figure 1. Conclusion Based on our study findings, we conclude that dyspnea on exertion is an independent predictor of mortality in patients with no baseline CV or respiratory disorders. Patients presenting with dyspnea alone as a presenting compliant should be evaluated thoroughly and treated accordingly to reduce the associated mortality outcomes. Figure 1. Kaplan-Meier Plot Funding Acknowledgement Type of funding source: None

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Background: Diffuse large B-cell lymphoma (DLBCL) is frequently curable after frontline therapy, however, relapses can occur after achievement of a PET-negative complete remission (CR). Early detection of relapse may be associated with improved outcomes with second-line curative intent therapy or novel therapies. Controversy exists regarding the utility of post-therapy surveillance imaging which is associated with patient (pt) anxiety, radiation exposure, false-positive results, and cost. A retrospective study found that serial minimal residual disease (MRD) monitoring during DLBCL surveillance could identify pts at risk of relapse before clinical evidence of disease (Roschewski, Lancet Oncol, 2015). In this multicenter prospective study, we assessed whether a next-generation sequencing (NGS)-based MRD assay could be used for early detection of molecular relapse in DLBCL. Methods: Eligible pts with DLBCL or high-grade B-cell lymphoma (HGBCL) who received anthracycline-containing chemotherapy were enrolled across five cancer centers. In pts who achieved a PET-negative CR, serial peripheral blood samples were obtained every 3 months (mos) and CT scans every 6 mos for 2 years (yrs) post-treatment. The clonoSEQ® next generation sequencing (NGS) MRD assay (Adaptive Biotechnologies, Seattle, WA) that leverages multiplex PCR followed by NGS to identify and track rearrangements of IgH, V-J, D-J and IgK/L loci and translocations in Bcl1/2-IgH was used. MRD positive was defined as any detectable rearrangement and MRD negative as no evidence of rearrangement. We also reported MRD positivity above the limit of detection (LOD) (observations required to have 95% reproducibility). Interim futility analysis was performed after approximately 50% of anticipated relapses occurred to assess the preliminary sensitivity of the assay. Progression-free survival (PFS) was defined as time from treatment start date to relapse or death. Results: 501 pts were enrolled and 401 were evaluable (pre-treatment tumor pathology available, completed frontline treatment, and achieved PET-negative CR at end-of-treatment). Baseline characteristics were median age of 62 yrs (range 19-95), male sex 58%, advanced stage 61%, and poor-risk by R-IPI 40% (Table 1). Histologies included DLBCL, NOS (86%), primary mediastinal B-cell lymphoma (6%), HGBCL (5%), T-cell rich B-cell lymphoma (1%), and other (1%). Pts received regimens including RCHOP x 6 cycles (36%), REPOCH x 6 cycles (20%), clinical trial (15%), combined modality therapy (RCHOP+RT) (10%), and other RCHOP variations (19%). Among the 401 evaluable pts, 44 relapses have occurred as of June 1, 2020. In 47% of pts (18/38), clinical relapse was detected using surveillance imaging alone (typically CT CAP with IV contrast) in an otherwise asymptomatic pt with a normal physical exam and laboratory evaluation. Clinical relapse was detected by clinical symptoms alone in 11% (4/28), by the evaluation of an oncologist alone in 0%, and by imaging and clinical symptoms and/or evaluation by an oncologist in 42% (16/38) (missing data in 6 pts). With a median follow-up of 2.2 yrs, the 2-yr PFS was 88.1% (84.8, 91.4) (Figure 1). Advanced age, advanced stage, and poor-risk R-IPI were associated with inferior PFS. Of the 44 relapses, 43 pts were included in the interim analysis and tumor-specific clonotypes were identified in 39 pts (91%). In 56% (22/39), the MRD assay was positive at or before clinical relapse. In 38% (15/39), the MRD assay was positive above the limit of detection at or prior to clinical relapse, with only 10 relapses detected more than 3 mos prior to relapse, reflecting the poor clinical sensitivity of the assay. The NGS-MRD assay was more sensitive in the acellular (plasma cell-free DNA) than in the cellular (circulating leukocytes) compartment. Results: Overall outcomes are excellent for DLBCL and HGBCL pts who achieve PET-negative complete remission. In interim analysis, surveillance MRD assessment using the clonoSEQ® assay fails to consistently identify pts at risk of recurrence before clinical evidence of relapse in DLBCL. In a prospective analysis, a substantial proportion (47%) of clinical relapses are detected by imaging in asymptomatic pts, supporting the value of CT surveillance imaging in DLBCL, particularly for pts with advanced stage or high-risk disease. Additional analyses are forthcoming for MRD assessment in all pts, including those in remission. Disclosures Kumar: Celgene: Research Funding; Pharmacyclics: Research Funding; Adaptive Biotechnologies,: Research Funding; AbbVie: Research Funding; Seattle Genetics: Research Funding; Celgene: Honoraria, Other: Honoraria for Advisory Board; Astra Zeneca: Honoraria, Other: Honoraria for Advisory Board; Kite Pharmaceuticals: Honoraria, Other: Honoraria for Advisory Board. Westin:Kite: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy; Astra Zeneca: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; 47: Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Nowakowski:Curis: Consultancy; Seattle Genetics: Consultancy; Nanostrings: Research Funding; MorphoSys: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Kite: Consultancy; Denovo: Consultancy; Kymera: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other. Lossos:Verastem: Consultancy, Honoraria; Seattle Genetics: Consultancy, Other; NCI: Research Funding; Stanford University: Patents & Royalties; Janssen Biotech: Honoraria; Janssen Scientific: Consultancy, Other. Batlevi:Life Sci, GLG, Juno/Celgene, Seattle Genetics, Kite: Consultancy; Janssen, Novartis, Epizyme, Xynomics, Bayer, Autolus, Roche/Genentech: Research Funding. Drullinsky:Roche: Research Funding; Novartis: Research Funding. Gerecitano:Janssen: Current Employment. Hamlin:Celgene: Consultancy; Karyopharm: Consultancy; Juno Therapeutics: Consultancy; Portola: Research Funding; Molecular Templates: Research Funding; Incyte: Research Funding; J&J Pharmaceuticals: Research Funding; Portola Pharmaceutics: Consultancy. Horwitz:ASTEX: Consultancy; Affirmed: Consultancy; Vividion Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; Miragen: Consultancy; Kura Oncology: Consultancy; Janssen: Consultancy; GlaxoSmithKline: Consultancy; Daiichi Sankyo: Research Funding; C4 Therapeutics: Consultancy; Beigene: Consultancy; Portola: Consultancy, Research Funding; Mundipharma: Consultancy; Innate Pharma: Consultancy; Corvus: Consultancy; Trillium: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Forty Seven: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Aileron: Consultancy, Research Funding; ADCT Therapeutics: Consultancy, Research Funding. Jacob:Adaptive Biotechnologies: Current Employment, Current equity holder in publicly-traded company. Joffe:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees. von Keudell:Bayer: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding. Lahoud:MorphoSys: Other: Advisory Board. Matasar:Bayer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Rocket Medical: Consultancy, Research Funding; Teva: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Daiichi Sankyo: Consultancy; IGM Biosciences: Research Funding; Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Immunovaccine Technologies: Honoraria, Research Funding; Merck: Consultancy; Juno Therapeutics: Consultancy; Genentech, Inc.: Consultancy, Honoraria, Research Funding. Mullins:Adaptive Biotechnologies: Current Employment, Other: shareholder. Noy:Pharmacyclics: Research Funding; NIH: Research Funding; Rafael Pharma: Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy; Medscape: Consultancy; Targeted Oncology: Consultancy; Morphosys: Consultancy. Straus:Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; ASH: Other: Conference in December 2019 on HL to other physicians during ASH; Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer; OncLive: Speakers Bureau; Takeda Pharmaceuticals: Research Funding, Speakers Bureau; NY Lymphoma Rounds: Consultancy; Targeted Oncology: Consultancy, Speakers Bureau; Imedex, Inc.: Speakers Bureau; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees. Younes:Takeda: Consultancy; HCM: Consultancy; AstraZeneca: Current Employment; Novartis: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Consultancy; Epizyme: Consultancy; BMS: Consultancy; BioPath: Consultancy; Curis: Consultancy. Zelenetz:MEI Pharma: Research Funding; MorphoSys: Research Funding; Sandoz: Research Funding; Celgene: Research Funding; Roche: Research Funding; Gilead: Research Funding; Genentech/Roche: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Adaptive Biotechnology: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees.

Background: The prognosis for patients (pts) with relapsed T-ALL and T-LL is dismal; the primary goal of T-ALL/T-LL treatment is to prevent relapse. AALL1231 was a COG phase 3 clinical trial that randomized children and young adults (age 1-30 years) to a modified augmented BFM (aBFM) backbone +/- the proteasome inhibitor bortezomib during induction and delayed intensification (DI) (1.3mg/m2 x 4 doses per block). Bortezomib was tested in frontline therapy based on strong preclinical data and data in relapse on COG AALL07P1. Pts were stratified as standard (SR), intermediate (IR), or very high risk (VHR), primarily based on disease response: morphologic and minimal residual disease (MRD) at end induction and end consolidation (T-ALL) and radiographic response (T-LL). To eliminate cranial radiation (CXRT) in all pts, (except VHR: Day 29 M3 marrow or EOC MRD >0.1% or pts with overt CNS leukemia at diagnosis, CNS3), the aBFM backbone was modified to use dexamethasone (dex) as the sole corticosteroid and an extra pegaspargase dose was added in both induction and DI, following the MRC strategy. IR pts received a second interim maintenance (IM) phase (one Capizzi MTX; one HD-MTX). Following consolidation, VHR pts received 3 BFM high-risk intensification blocks in lieu of IM. Results: AALL1231 accrued 847 patients (824 eligible and evaluable) of 1400 anticipated from 2014 until early closure in 2017 when COG AALL0434 established that nelarabine (NEL) improved DFS in T-ALL (AALL1231 did not include NEL). The 3-year EFS for Arm A (no bortezomib) vs Arm B (bortezomib) were 81.7±2.4% and 85.1±2.2 % (HR=0.782, p=0.074) (3/31/20 data cut-off; see Table 1 for additional outcomes). SR and IR pts, who account for 95% of pts, had significantly improved EFS on Arm B as compared with Arm A. Yet, VHR patients had improved EFS on Arm A. Patients with T-LL had improved EFS and OS with bortezomib: 3-year EFS (76.5±5.9% vs 88.3±4.5%; p = 0.01); 3-year OS (78.0±5.8% vs 89.5±4.2%, p = 0.007). A similar improvement in EFS and OS was not seen in T-ALL; however, with longer follow-up this may change. No excess toxicity was seen on Arm B. A dex-based Induction did result in lower MRD rates; more T-ALL pts on AALL1231 had Day 29 MRD <0.1% as compared with AALL0434 which used a prednisone-based Induction (AALL1231 Arm A: 69.6%; Arm B: 72.2%; AALL0434: 64.6%; p = 0.02). However, this did not translate into improved survival. Indeed OS, but not EFS was worse on AALL1231 than AALL0434. On-going analyses are investigating the increased mortality on AALL1231, but preliminary analyses suggest a combination of increased toxic deaths and overall poor outcome in the VHR group. On AALL0434, 90.8% of T-ALL pts received CXRT. On AALL1231, 9.5% of subjects were scheduled to receive CXRT (CNS3 T-ALL/T-LL: 5.7%; VHR T-ALL: 4.1%). A comparison of AALL0434 pts that received CXRT with similar AALL1231 pts not receiving CXRT on AALL1231 demonstrated similar EFS (p = 0.14) and OS (p = 0.42) (Table 2). CNS relapse rates were higher in these pts on AALL1231 (4.5%) as compared with AALL0434 (1.7%), but overall relapse rates were the same (6.5% vs 6.4%). Notably the benefit of NEL in AALL0434 was due to reduction of CNS relapses. 128 AALL1231 pts came off protocol therapy after the study was closed for physician or patient/parent choice. Data collection is underway to understand the reasons for removal, including if it was to receive NEL. Conclusions: Outcomes for SR and IR pts with T-ALL and T-LL treated with bortezomib were excellent despite the elimination of prophylactic CXRT. Bortezomib significantly improved 3-year EFS for these groups, comprising ~95% of pts. Outcomes for VHR pts were dismal and worse on the bortezomib arm. T-LL pts had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. This is the first trial to demonstrate an OS benefit for de novo pediatric T-LL with a new agent; however, longer follow-up is needed. Therapy intensification allowed elimination of CXRT in the majority of pts without excessive relapse. These results should be interpreted cautiously as the 3-yr OS on AALL1231 was inferior to AALL0434. Nevertheless, incorporating bortezomib into standard therapy for de novo T-LL appears advantageous. Future COG T-ALL/T-LLy trials will build on the positive findings from AALL0434 and AALL1231, balancing intensity while mitigating toxicity to maintain high cure rates without routine cranial radiation. (MLL, SPH, EAR contributed equally) Disclosures Teachey: Amgen: Consultancy; Janssen: Consultancy; La Roche: Consultancy; Sobi: Consultancy. Dunsmore:Dexcom: Current equity holder in publicly-traded company. Galardy:Abbott: Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company. Harker-Murray:Regerenon Pharmaceuticals: Consultancy. Hermiston:Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Shimano:Novartis: Research Funding; Daiichi Sankyo: Research Funding; Pfizer: Research Funding; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. McKay:Immunogen: Current Employment. Bollard:Mana Therapeutics: Other: IP. Loh:Medisix Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Institutional Research Funding. Hunger:Novartis: Consultancy; Amgen Inc.: Current equity holder in publicly-traded company, Honoraria. Raetz:Celgene/BMS: Other; Pfizer: Research Funding. OffLabel Disclosure: Bortezomib for the treatment of acute lymphoblastic leukemia under an IND

Background: Chimeric Antigen Receptor (CAR) T-cell therapy has changed the treatment landscape for patients with Non-Hodgkin Lymphoma (NHL). Despite the excellent responses in relapsed or refractory (R/R) aggressive NHL (aNHL), the outcome of patients (pts) that fail CAR T-cell therapy remains poor, and there is not a clear path for management of their disease. Methods: We conducted a retrospective analysis of aNHL pts treated with axicabtagene ciloleucel (axi-cel) at the Mayo Clinic campuses in Arizona and Florida between June 2018 and August 2020. We evaluated the predisposing factors, management, toxicities, and response after CAR T-cell therapy failure. Statistical calculations using parametric tests were performed, and survival curves were estimated using the Kaplan-Meier method and compared statistically using the log-rank test and Pearson's correlation. Results: Thirty-four pts with aNHL received axi-cel. The median age was 53 years [IQR 42-63], and 62% were male. All pts received inpatient axi-cel infusions and the median length of hospital stay was 14 days (IQR: 11-17). Cytokine Release Syndrome (CRS) was observed in 91% of pts (3% grade ≥3), while Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) was observed in 41% (24% grade ≥3). At day 30 response assessment, 16 pts (47%) had complete responses (CR), 9 (26%) had a partial response (PR), 4 (12%) had stable disease (SD), 4 (12%) showed progression with primary refractory disease (PD) and 1 (3%) died before assessment due to grade 5 ICANS (Table 1). After a median follow-up of 178 days, we observed PD in 12 (35%) pts. The median time-to-progression was 72 days (IQR 58-93) and most of the pts (83%) progressed during the first 3 months. None of the patients with more than 5 months of sustained response developed progression of disease. The likelihood of progression during the first 6 months after axi-cel infusion was 19%, 57%, 50% for pts that initially achieved a CR, PR, SD, respectively. Expression of CD19 was observed in 66% (4/6) of pts with available biopsies after axi-cel suggesting a failure mechanism other than antigen escape. The mortality rate of the R/R aNHL group was 58% with a median survival time of 83 days (IQR: 50-109). There was no association between age, stage, number of previous therapies, time from previous therapy to axi-cel infusion, time from apheresis to infusion, use of tocilizumab, or steroids with progression of disease. Of note, no correlation between CRS or ICANS with progression of disease was found (2-way ANOVA test F (1, 4) = 3.802, p=0.1230). Maintaining a response to axi-cel treatment (CR, PR, or SD) for ≥ 3 months was a strong predictor of durable response with an HR of 0.05 (p= <0.0001). Eleven R/R pts received subsequent therapies with a median time to retreatment of 76 days. Those treatments included: Radiotherapy (n=7), pembrolizumab (n=3), polatuzumab-rituximab with (n=3) and without (n=1) bendamustine, obinutuzumab with (n=1) or without (n=1) lenalidomide, Hyper-CVAD (n=2), R-GemOx (n=1), rituximab with lenalidomide (n=1) and intrathecal methotrexate (n=1). Only 2 (17%) patients have responded to salvage therapy achieving PR (one patient treated with radiotherapy and the other with rituximab-lenalidomide after two other salvage therapies). Conclusion: Our experience demonstrates the majority of aNHL patients respond to axi-cel. If patients maintain their response for more than 3 months, the likelihood of progression is very low - 15%. Similar to what has been previously reported in the literature, our series showed that 35% of patients progressed after axi-cel, and subsequently have a poor prognosis with median survival after a relapse of only 83 days (IQR: 50-109). Therapy options following axi-cel were limited due to severe cytopenias, only 2 of 11 patients have responded to salvage therapy, suggesting that conventional treatments are probably not effective/safe in this high-risk group of patients. Interestingly, the majority of R/R pts with available biopsies showed persistent CD19 expression suggesting that CAR T-cell exhaustion, poor in vivo expansion, and inhibitory signals of the tumor microenvironment may contribute to resistance. Additional strategies for monitoring of axi-cel persistence and its immunophenotypic profile could be helpful for prognosis and management of CAR T-cell pts receiving axi-cel. Disclosures Kharfan-Dabaja: Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Castro:Fate Therapeutics: Research Funding; Kite Pharma: Research Funding; Pharmacyclics: Research Funding.

Introduction Primary mediastinal large B cell lymphoma (PMBCL) is a rare non-Hodgkin lymphoma (NHL) with a female predominance; often presenting with a large anterior mediastinal mass. Though PMBCL has clinical and molecular features overlapping with Hodgkin lymphoma, it is a distinct entity defined by the World Health Organization classification. PMBCL is heterogeneously treated, and most patients receive front line therapy with either rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with radiotherapy (RT), or the more intensive etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with rituximab (EPOCH-R) regimen. Diagnosis of PMBCL is made using clinicopathologic criteria and radiographic imaging, however gene expression profiling (GEP) studies reveal a characteristic genotypic signature distinct from diffuse large B cell lymphoma (DLBCL). Molecular classification of PMBCL using the Lymph3Cx assay from formalin-fixed paraffin-embedded tissue (FFPE) is feasible, reproducible, and highly concordant in a training and validation cohort (Mottok et al. Blood 2018). Using a multicenter cohort of patients, we sought to estimate the rate of mis-match among patients with a clinical diagnosis of PMBCL using Lymph3Cx, and describe treatment selections and outcomes for each group. Methods Patients were identified from a cohort of patients with newly diagnosed NHL from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource, and the Lymphoma Epidemiology of Outcomes cohort. Patients were enrolled between 2002-2019, and included if they had clinically defined PMBCL. FFPE was retrieved from hematopathology archives of participating academic centers. All diagnoses of PMBCL were based on expert hematopathology review at the time of therapy, and all cases underwent classification by GEP using the Lymph3Cx assay. Lymph3Cx was performed in the clinical lab at the Mayo Clinic in Arizona: Contiguous unstained sections were deparaffinized and macrodissected to enrich for tumor content before RNA isolation;100-200 ng of total RNA was used in an nCounter Elements XT, hybridized, and processed the following day using the nCounter FLEX system. Raw counts were processed through the Lymph3Cx algorithm and results reported as probability of PMBCL (≥0.90 as PMBCL, ≤0.10 as DLBCL all other results "Unclear PMBCL/DLBCL") (A. Mottok et al, Blood, 2018). For cases classified as DLBCL, the Lymph2Cx cell-of-origin classifier results was reported (Scott et al, JCO, 2016). Time to event endpoints were described with Kaplan-Meier plots by groups defined by mismatch status and compared with a logrank test. Binary outcomes will be presented with 90% exact confidence intervals. Results Fifty patients were identified. Median age was 35 years (range 19-70). Sixty four percent were women. Median follow up was 47 months. Treatments included R-CHOP (44%), EPOCH-R (44%), and MACOP-B [methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin] (6%), other (4%). Ten patients (20%) had events (defined as progression or death). Three patients in the entire cohort (6%) died. The Kaplan-Meier estimated survival at 47 months (median follow-up) is 92%. The Lymph3Cx assay yielded gene expression data of sufficient quality in 47/50 cases (94%, 90% CI=85.2, 98.3%). Of 47 cases clinically identified as PMBCL, 5 unclear were DLBCL/PMBCL and 1 was Germinal Center B cell subtype of DLBCL. Among these 6 patients, 4 received R-EPOCH (66%), 1 received R-CHOP (16.6%). One patient had missing treatment data. One patient had an event requiring subsequent therapy; all patients remain alive. Conclusions Using 47 patients with PMBCL defined by histology, clinical and radiographic findings, and molecular features, we demonstrate high concordance between clinical phenotype and molecular genotype of PMBCL by Lymph3Cx. Among the 6 patients not classified as PMBCL, most received R-EPOCH. Differences in outcome by mis-match status await longer follow-up and further accrual of subjects to our data base. Our data suggest molecular genotyping may have a role in mediastinal presentations of large cell lymphoma to optimize treatment decision making. Disclosures Maurer: Nanostring: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding. Flowers:AbbVie: Consultancy, Research Funding; Kite: Research Funding; Burroughs Wellcome Fund: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; V Foundation: Research Funding; Bayer: Consultancy; National Cancer Institute: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Astellas: Consultancy; Bayer: Consultancy; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy; Roche: Other: Travel expenses; Seattle Genetics: Research Funding.

Background:Case reports suggest photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an effective treatment for refractory mycosis fungoides (MF). No prospective trials have examined the use of ALA-PDT in MF. Objective:We aimed to assess the efficacy of ALA-PDT in refractory MF. Methods:This was a prospective study at Mayo Clinic in Scottsdale, Arizona in patients ≥ 18 years with plaque-stage treatment-refractory MF. Monthly sessions of ALA with blue light PDT were administered for up to six months. Responses were measured by Composite Assessment of Index Lesion Severity (CAILS) and Physician Global Assessment (PGA). Ad hoc analysis with modified CAILS (mCAILS) was performed, eliminating hyperpigmentation from scoring. Results:Eleven patients (30 total lesions) were treated. Six patients completed the trial per protocol. Objective response rates were 36.4% by PGA (10.9-69.2%), 18.2% by CAILS (2.3-51.8%), and 36.4% by mCAILS (10.9-69.2%). Limitations:Five patients did not complete all six PDT cycles per protocol, possibly accounting for reduced efficacy. Conclusion:ALA-PDT with blue light irradiation was moderately effective and well tolerated in refractory plaque stage MF. Lower response rates compared to similar trials may be partially explained by utilization of strict lesional assessment criteria and other variations in methodology. Disclosures Mangold: MiRagen:Research Funding;Sun Pharma:Research Funding;Elorac:Research Funding;Kirin:Membership on an entity's Board of Directors or advisory committees;Solagenix:Research Funding. OffLabel Disclosure: Photodynamic therapy is a two-step therapy in which a drug that acts as a photosensitizer is administered to target a diseased tissue, followed by illumination with visible light to activate the drug and destroy the target tissue. PDT has been used to treat internal cancers as well as treatment of cancer and precancer of the skin.