Abstract: In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed/refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared to the L-MIND registration clinical trial for TL.

Abstract: Systemic immunosuppressive treatment of pediatric chronic anterior uveitis ( CAU ), both juvenile idiopathic arthritis–associated and idiopathic anterior uveitis, varies, making it difficult to identify best treatments. The Childhood Arthritis and Rheumatology Research Alliance ( CARRA ) developed consensus treatment plans ( CTP s) for CAU for the purpose of reducing practice variability and allowing future comparison of treatments using comparative effectiveness analysis techniques. Methods A core group of pediatric rheumatologists, ophthalmologists with uveitis expertise, and a lay advisor comprised the CARRA uveitis workgroup that performed a literature review on pharmacologic treatments, held teleconferences, and developed a case‐based survey administered to the CARRA membership to delineate treatment practices. We held 3 face‐to‐face consensus meetings using nominal group technique to develop CTP s. Results The survey identified areas of treatment practice variability. We developed 2 CTP s for the treatment of CAU , case definitions, and monitoring parameters. The first CTP is directed at children who are naive to steroid‐sparing medication, and the second at children initiating biologic therapy, with options for methotrexate, adalimumab, and infliximab. We defined a core data set and outcome measures, with data collection at 3 and 6 months after therapy initiation. The CARRA membership voted to accept the CTP s with a 〉 95% approval (n = 233). Conclusion Using consensus methodology, 2 standardized CTP s were developed for systemic immunosuppressive treatment of CAU . These CTP s are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTP s in a prospective comparison effectiveness study should improve outcomes by identifying best practice options.

Abstract: Background Allogeneic (off the shelf) chimeric antigen receptor (CAR) T-cell therapy addresses the logistical challenges, availability (including insufficient T-cell yields from low baseline absolute lymphocyte count), and variable product quality of autologous CAR T therapy. ALLO-501A is a genetically modified anti-CD19 AlloCAR T™ cell product that uses TALEN ® gene editing to disrupt the T-cell receptor alpha constant gene (TRAC) and the CD52 gene to reduce the risk of graft-versus-host disease (GvHD) and permit the use of ALLO-647, an anti-CD52 monoclonal antibody (mAb), for selective and transitory host lymphodepletion (LD). Here we present an update on the preliminary safety, efficacy, and correlative data. ALLO-501A uses Cellectis technologies. Methods ALPHA2 (NCT04416984) is a single-arm, open-label, Phase 1/2 trial of ALLO-501A in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL including [R/R] diffuse LBCL [DLBCL] , transformed follicular lymphoma [tFL], marginal zone lymphoma [tMZL] , primary mediastinal B-cell lymphoma [PMBCL], follicular lymphoma grade 3B [FL3B] ) who received ≥2 prior lines of therapy (including an anthracycline and anti-CD20 mAb), have an ECOG performance status of 0 or 1. Subjects with donor specific antibodies are excluded. Following LD with ALLO-647, fludarabine 30 mg/m 2/d x 3d (F), and cyclophosphamide 300 or 500 mg/m 2/d x 3d (C), either a single (40 [DL1] or 120 [DL2] x 10 6 viable CAR T cells) or consolidation dose of ALLO-501A (DL2) are given. For consolidation dose, pts with ≥stable disease (SD) at day 28 receive consolidation with second ALLO-647 (no chemo) for LD and ALLO-501A (DL2) cell infusion. Results As of July 9, 2021, 20 pts were enrolled; 15 pts were treated with ALLO-501A (12 evaluable and 3 pending D28 assessment); 3 pts pending treatment; 2 pts withdrew due to adverse event (AE)/progressing disease (PD) prior to dosing. Patients were heavily pretreated with advanced-stage disease (Stage III: 4 [22.2%], Stage IV: 8 [44.4%] ), median number of prior treatments was 3 with a high of 7. Three pts (16.7%) had primary refractory disease. Safety profile was manageable in both single dose and consolidation cohorts. Events of interest in the single dose cohort have been previously reported (ASCO 2021). In the consolidation cohort (13 enrolled, 9 pts dosed thus far), no cytokine release syndrome (CRS), no GvHD, no immune effector cell-associated neurotoxicity syndrome (ICANS), no dose-limiting toxicities (DLTs), no dose reductions, no Grade (Gr) 3+ infections and no related serious adverse events (SAEs) occurred, and infusion-related reactions were Gr 1. Among all treated, cytopenias were the most common AE and occurred in 72% of pts. Of the 12 evaluable pts (6 each treated in the single dose and consolidation dose cohort), both the overall response rate (ORR) and complete response (CR) were 50% (95% CI: 21.1, 78.9). In the consolidation cohort, both ORR and CR rate were 66.7% (95% CI: 22.3, 95.7) with 3/3 partial responses (PRs) converting to CR after consolidation; 1 pt had CR at days 28 and 56 post consolidation and 2 pts had PD at month 1 and did not receive consolidation. In single dose cohort, 2 pts have ongoing CR at 9 and 12+ months. CAR T expansion was greater in pts who achieved a CR with a geometric mean area under the curve (AUC) at D1-28 of 206,990 copies/ug*days (n=6; GSD 4.94) compared to pts who did not achieve a CR with AUC at D1-28 of 3,571 copies/ug*days (n=3; GSD 2.41). Pts who received the consolidation dose continued to have CAR T expansion after the 2 nd CAR T infusion with geometric mean AUC from D30-56 of 92,893 copies/ug*days (n=4; GSD 5.42). Conclusions ALLO-501A with consolidation dosing demonstrated comparable safety and an improved efficacy profile compared to single dosing with all 4 pts who received consolidation remaining in CR. Persistence of CAR T at D28 and expansion after consolidation dose was observed in addition to the observed deepening of responses in pts whose initial response was PR. Additional follow up is needed to determine whether consolidation also improves the durability of response. Consolidation was well tolerated and given the generally favorable overall safety profile, ALLO-501A may have the potential to be given in the outpatient setting. Enrollment is ongoing. Updated efficacy and follow-up will be presented at the meeting. Currently, an ALLO-501A Phase 2 trial is planned. Disclosures Locke: Cowen: Consultancy; Umoja: Consultancy, Other; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Janssen: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Legend Biotech: Consultancy, Other; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; EcoR1: Consultancy; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties. Hamadani: Janssen, Incyte, ADC Therapeutics, Omeros, Morphosys, Kite: Consultancy; Sanofi, Genzyme, AstraZeneca, BeiGene: Speakers Bureau; Takeda, Spectrum Pharmaceuticals and Astellas Pharma: Research Funding. Frank: Allogene Therapeutics: Research Funding; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Research Funding. Popplewell: Novartis: Other: Travel; Pfizer: Other: Travel; Hoffman La Roche: Other: Food. Abramson: Bluebird Bio: Consultancy; Kymera: Consultancy; BeiGene: Consultancy; Incyte Corporation: Consultancy; Astra-Zeneca: Consultancy; Allogene Therapeutics: Consultancy; Seagen Inc.: Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; Morphosys: Consultancy; Kite Pharma: Consultancy; C4 Therapeutics: Consultancy; Genmab: Consultancy; EMD Serono: Consultancy; Bristol-Myers Squibb Company: Consultancy, Research Funding; Genentech: Consultancy. Munoz: Pharmacyclics/Abbvie: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Gilead/Kite Pharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Juno/Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Alexion: Consultancy; Beigene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Debiopharm: Consultancy; Karyopharm: Consultancy; Genmab: Consultancy; ADC Therapeutics: Consultancy; Epizyme: Consultancy; Servier: Consultancy; Merck: Research Funding; Portola: Research Funding; Incyte: Research Funding; Genentech: Research Funding, Speakers Bureau; Millennium: Research Funding; Targeted Oncology: Honoraria; OncView: Honoraria; Physicians' Education Resource: Honoraria; Roche: Speakers Bureau; AstraZeneca: Speakers Bureau; Verastem: Speakers Bureau; Acrotech/Aurobindo: Speakers Bureau. Shin: Allogene Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Loomis-Navale: Allogene: Current Employment, Current equity holder in publicly-traded company. Miklos: Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Patents & Royalties. OffLabel Disclosure: Discussion of fludarabine and cyclophosphamide in combination with ALLO-647 as conditioning regimen prior to administration of ALLO-501A in patients with R/R LBCL.

Abstract: 2529 Background: Allogeneic CAR T cell therapy addresses logistical/manufacturing challenges inherent in autologous (auto) CAR T therapy. ALLO-501A, which uses Cellectis technologies, is an allogeneic anti-CD19 CAR T cell product whose a) disrupted TCRα gene may reduce GvHD risk, and b) edited CD52 gene may permit use of ALLO-647 (a humanized anti-CD52 mAb) to selectively deplete host T cells. Methods: The ongoing ALPHA2 study is a single-arm, open-label, 2 phase study of ALLO-501A in non-HLA matched patients (pts) with R/R LBCL and ≥2 prior lines of therapy. Prior auto CD19 CAR T therapy is allowed if tumors remain CD19 + . Following lymphodepletion (LD) with ALLO-647 (60 mg or 90 mg), fludarabine 30 mg/m 2 /d x 3d (Flu), and cyclophosphamide 300 mg/m 2 /d x 3d (Cy), escalating doses of ALLO-501A (40 [DL1] or 120 [DL2] x 10 6 viable CAR T cells) were administered. Retreatment was allowed for PD or SD with suboptimal CAR T expansion. Pts who had ≥SD at D28 could receive a second dose in a consolidation cohort. Phase 1 assessed safety/tolerability and cell kinetics of escalating doses of ALLO-501A following LD. Results: By 1/15/21, 11/11 enrolled pts received ALLO-647 (60 mg: n=6; 90 mg: n=5). Mean duration from enrollment to start of therapy was 6 days. After LD, 1 and 9 pt(s) were treated with ALLO-501A at DL1 and DL2, respectively; 1 pt developed CNS lymphoma and was not treated. Of 10 pts treated, 1 pt received retreatment and 4 pts were enrolled in the consolidation cohort. Pts had a median age of 60 years; 8 were ≥ stage III at diagnosis, 5 had IPI scores ≥3, and 3 had baseline LDH 〉 2x ULN. Median number of prior therapies was 3 (range 2 – 7); 3 pts had received auto CD19 CAR T cell therapy. 4/8 evaluable pts had rapidly PD at study entry. Median FU was 1.7 months. No dose modifications were required and no pt experienced DLTs. The most common AEs were anemia, leukopenia, neutropenia and thrombocytopenia (73%); and lymphopenia (64%). No GvHD or ICANS were reported. CRS was seen in 2 (18%) pts, both Grade 〈 3. Infusion-related reactions, all grade 〈 3, were observed in 4 (36%) pts. D28 response data are available for 8 pts: 1 died of PD before D28; 4 additional pts had PD, including 2 who progressed 2 and 3 mos. after auto CAR T; 1 had SD; and 2 (both DL2) had CR. Of those in CR, 1 had peak ALLO-501A expansion at D14, persistence until D42, and ongoing CR at 4 mo; 1, with a 4-mo response to prior auto CAR T, had peak expansion at D28 and remains in ongoing CR at D56 after ALLO-501A with pending persistence. Conclusions: This dose escalation cohort contained heavily pretreated, actively progressing pts, some of whom had failed auto CAR T. Preliminary data suggest an acceptable safety profile following ALLO-501A and ALLO-647 and early signs of efficacy in LBCL. Enrollment into the consolidation cohort is ongoing; updated clinical/biomarker data of resistance and clinical activity will be presented. Clinical trial information: NCT04416984.

Abstract: 122 Background: Retinoblastoma (Rb) survivors are at risk for adverse oculo-visual outcomes. Limited data are available regarding long-term visual functioning among adult Rb survivors. Methods: Rb survivors, diagnosed from 1932–1994 and treated in New York, completed a comprehensive questionnaire that included the National Eye Institute Visual Function Questionnaire (VFQ-25), which measures self-reported vision-targeted health in individuals with chronic eye diseases. Items are scored from 0–100 with 100 representing the best possible score. Results: 470 adult Rb survivors participated (53.6% with bilateral disease; mean age at study 43.3 yrs, standard deviation [SD] 11); 86% had at least one eye removed (one eye: 74.5%; both eyes: 11.5%) and 53.4% were treated with radiotherapy. 61.3% rated their eyesight as excellent/good while 16.5% reported complete blindness. Among Rb survivors with some vision, 4% described staying home “most of the time” due to their eyesight and 12% reported often feeling frustrated due to their visual status. The overall VFQ composite score for all Rb survivors was 89.2 (SD 10.1) [unilateral Rb survivors: 92.2 (SD 6.3); bilateral Rb survivors: 84.1 (SD 13.0); p 〈 0.001).Survivors with bilateral disease were significantly more likely to report inferior visual functioning in all domains when compared to those with unilateral disease (Table 1). Conclusions: Rb-related ocular problems continue to impact survivors’ functional status into adulthood, particularly among those with bilateral disease. [Table: see text]

Abstract: Survival rates for individuals diagnosed with retinoblastoma (RB) exceed 95% in the United States; however, little is known about the long-term psychosocial outcomes of these survivors. Patients and Methods Adult RB survivors, diagnosed from 1932 to 1994 and treated in New York, completed a comprehensive questionnaire adapted from the Childhood Cancer Survivor Study (CCSS), by mail or telephone. Psychosocial outcomes included psychological distress, anxiety, depression, somatization, fear of cancer recurrence, satisfaction with facial appearance, post-traumatic growth, and post-traumatic stress symptoms; noncancer CCSS siblings served as a comparison group. Results A total of 470 RB survivors (53.6% with bilateral RB; 52.1% female) and 2,820 CCSS siblings were 43.3 (standard deviation [SD], 11) years and 33.2 (SD, 8.4) years old at the time of study, respectively. After adjusting for sociodemographic factors, RB survivors did not have significantly higher rates of depression, somatization, distress, or anxiety compared with CCSS siblings. Although RB survivors were more likely to report post-traumatic stress symptoms of avoidance and/or hyperarousal (both P 〈 .01), only five (1.1%) of 470 met criteria for post-traumatic stress disorder. Among survivors, having a chronic medical condition did not increase the likelihood of psychological problems. Bilateral RB survivors were more likely than unilateral RB survivors to experience fears of cancer recurrence (P 〈 .01) and worry about their children being diagnosed with RB (P 〈 .01). However, bilateral RB survivors were no more likely to report depression, anxiety, or somatic complaints than unilateral survivors. Conclusion Most RB survivors do not have poorer psychosocial functioning compared with a noncancer sample. In addition, bilateral and unilateral RB survivors seem similar with respect to their psychological symptoms.