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Introduction: FL is the most common indolent non-Hodgkin lymphoma in the Western world. FL may cause disease-related symptoms, and patients with high-risk disease usually require systemic therapy. BR is commonly used as first-line therapy for high-risk FL, and the addition of bortezomib to a BR backbone has been studied (Evens A et al. Clin Can Res 2020). Little is known about how these therapeutic options impact patients' health-related quality of life (HRQL). To fill this gap, patient-reported outcomes (PROs) were administered to patients enrolled on E2408 to quantify symptom burden and effects of BR versus BVR induction on HRQL. Methods: Patients (n=258) randomized to receive 6 cycles of BR or BVR induction completed PROs assessing neurotoxicity (FACT/GOG-Ntx) at the beginning of each treatment cycle. Additional PROs measuring fatigue (FACT-F), lymphoma-specific concerns (FACT-Lym) and HRQL (Functional Assessment of Cancer Therapy-General; FACT-G) were completed at baseline, mid-treatment (MT; cycle 3/4) and end of induction (EOI; cycle 6). Paired t-test was used to assess PRO score changes from baseline to MT and EOI within BR or BVR group. Two-sample t-test was used to compare change scores between groups at MT and EOI, respectively. Univariate analyses with a linear model identified patient baseline characteristics and clinical factors (age, sex, stage, performance status, # extra nodal sites, FLIPI, GELF, bone marrow involvement, elevated LDH, palpable splenomegaly, B-symptoms, CRIS) associated with PRO change scores from baseline to EOI, adjusting for treatment group. A multivariate model was built with backward variable selection approach for each of the PROs. Results: As shown in Figure 1, compared with baseline, patients randomized to BVR reported significantly worse FACT/GOG-Ntx scores at cycle 4, which continued to end of induction (FACT/GOG-Ntx change scores -2.91 to -3.73; p < 0.001). Neurotoxicity remained stable for patients treated with BR (Ntx change scores -0.02 to -0.55). FACT-Fatigue scores indicated worse fatigue at MT compared to baseline for patients receiving BVR (-2.7, p<0.05), yet they remained stable for BR. FACT-Lym scores were significantly higher at MT (BR: 2.69, p<0.001; BVR: 2.71, p=0.007) and end of induction (BR: 3.32, p<0.001; BVR: 3.55, p<0.001) compared to baseline, signifying a reduction in lymphoma-related symptoms in both arms. FACT-G scores were comparable between treatment arms at each time-point and did not change significantly from baseline to end of induction. Univariate analyses among all patients identified older age and the absence of palpable splenomegaly at baseline as associated with worse FACT-Lym, FACT-Fatigue, and FACT-G change scores, signifying less improvement in lymphoma-related symptoms, fatigue and HRQL from baseline to end of induction (p<0.01). The presence of B-symptoms at baseline was associated with a greater reduction in lymphoma-related symptoms and fatigue from baseline to end of induction (p<0.01). Higher ECOG performance status was only associated with higher FACT-Fatigue change score, suggesting more improvement in fatigue for those with worse performance status at baseline. A multivariate model generated similar results. Conclusions: Despite worse treatment-related symptoms throughout induction, the addition of bortezomib was associated with comparable overall HRQL to those treated with BR. Both treatments were associated with a reduction in lymphoma-related symptoms from baseline to end of induction, likely contributing to stable HRQL throughout treatment despite treatment-related symptoms. Findings also suggest that a subgroup of patients, particularly those who are older, may experience fewer improvements in lymphoma-related symptoms. This underscores the potential need for closer monitoring and clinical management of these patients. Collectively, results are likely to be encouraging for patients experiencing lymphoma-related symptoms, for whom the symptom burden associated with treatment may be worth the trade-off given the potential for improved disease-related symptom control. Disclosures Evens: Merck: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; Epizyme: Consultancy, Honoraria, Research Funding; Mylteni: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding; Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy. Ansell:Trillium: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; AI Therapeutics: Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; ADC Therapeutics: Research Funding. Winter:Norvartis: Consultancy, Other: DSMB; Ariad/Takeda: Consultancy; CVS/Caremark: Consultancy; Delta Fly Pharma: Consultancy; Amgen: Consultancy; Epizyme: Other: DSMB; Merck: Membership on an entity's Board of Directors or advisory committees, Other: advisory board; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: advisory board. Cella:FACIT.org: Membership on an entity's Board of Directors or advisory committees, Other: President; Astellas: Consultancy, Honoraria; Pled Pharma: Research Funding; Janssen: Research Funding; Clovis: Research Funding; Alexion: Research Funding; Apellis: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Kiniksa: Consultancy; IDDI: Consultancy; BMS: Consultancy, Research Funding; ASAHI KASEI PHARMA CORP.: Consultancy; Oncoquest: Consultancy; Mei Pharma: Consultancy; Ipsen: Consultancy, Research Funding; Evidera: Consultancy; DSI: Consultancy, Research Funding; BlueNote: Consultancy; Abbvie: Consultancy, Research Funding; PROMIS Health Org: Membership on an entity's Board of Directors or advisory committees, Other. Kahl:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Acerta: Consultancy, Research Funding. Wagner:Celgene Inc.: Membership on an entity's Board of Directors or advisory committees; Connect Multiple Myeloma Registry: Membership on an entity's Board of Directors or advisory committees.

Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Castillo JJ, Am J Hematol. 2008) There has been a paucity of data suggesting that limited stage disease (Ann Arbor stage I-II) may have a more favorable prognosis. However, due to the rarity of this disease there have been no large-scale reviews to confirm this. Thus, many patients with limited stage disease are subject to the aggressive therapy recommendations based on the poor outcomes of PBL patients as a whole. (Loghavi S, J Hematol Oncol. 2015; NCCN Guidelines, version 2.2020; Al-Malki MM, BBMT. 2014) We attempted to determine the treatment patterns and outcomes of patients with limited stage PBL. Methods: We conducted a multi-center (13 US academic centers) retrospective study of patients with limited stage (Ann Arbor stage I-II) Plasmablastic lymphoma. Determination of limited stage and diagnosis of PBL was determined by the investigators at each individual center. Patients diagnosed between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcomes data were extracted by retrospective chart review. Kaplan Meier was utilized for time to event analysis. Results: Baseline characteristics are included in table 1. A total of 80 patients were identified with limited stage disease. With a median follow up of 34 months the 3-yr Progression free survival (PFS) and overall survival (OS) was 71.9% and 78.7% respectively (Figure 1A and 1B). Patients that received frontline chemotherapy with (n=29) and without RT (n=36) had a 3-yr PFS and OS of 84.6% and 96.2% as compared to 64.5% and 70.8%, respectively (Figure 2A and 2B; Figure 3A and 3B). The Hazard ratio (HR) for PFS and OS for chemo (reference) vs chemo-RT was 0.47 (95% CI 0.18-1.3; P=0.131) and 0.18 (95% CI 0.04-0.84; p=0.029) respectively. The HR for PFS and OS for CHOP (n=14, reference) vs EPOCH (n=33) based regimens was 0.37 (95% CI 0.11-1.2; p=0.106) and 0.36 (95% CI 0.079-1.6; p=0.182) respectively. Patients with stage I/IE disease (n=56) had a 3-yr PFS and OS of 73.1% and 81.2% respectively. Patients with stage II/IIE disease (n=24) had a 3-yr PFS and OS of 69.3% and 73.4% respectively. Patients that received aggressive treatment (n=17) with Hyper-CVAD based regimens and/or Auto-SCT as consolidation had a 3-yr PFS and OS of 63.6% and 72.7% respectively. Patients with concomitant HIV (n=16) had a 3-yr PFS and OS of 80.8% and 77.4% respectively. Seven patients received RT alone and 6 patients had surgical resection alone as frontline therapy; 1 patient received no therapy; 1 patient received HAART therapy only and remains in CR without any other treatment for PBL 29 months after diagnosis. There were 8 deaths (10%) related to PBL, 3 deaths (4%) related to treatment of PBL (2 during frontline chemo and 1 upon relapse with salvage chemo), and 9 deaths (11%) related to other causes. The 3-yr lymphoma free survival (LFS) of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (without including treatment related mortality (TRM) as an event) was 89.1%, 85.2%, and 100% respectively. The 3-yr LFS survival of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (including TRM as an event) was 85.1%, 80.0%, and 96.2% respectively. Discussion: Here we report the largest review to our knowledge of limited stage PBL. Outcomes appear to be excellent with 3-yr PFS and OS of 71.9% and 78.7% respectively and a 3-yr LFS of 89.1% (85.1% when attributing TRM as an event). There was no obvious benefit to receiving aggressive therapy with H-CVAD based regimens and/or Auto-SCT. Although this is a small, uncontrolled sample size the HR for OS was improved in patients receiving frontline chemo-RT vs chemo alone 0.18 (95% CI 0.04-0.84; p=0.029). However, this did not take into account TRM with or progression while receiving frontline chemotherapy. Patients who were HIV+ had similar PFS and OS outcomes compared to the entire cohort. This retrospective study clearly demonstrates the favorable outcomes in this patient population, especially in those able to receive definitive therapy for their disease. Disclosures Hess: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Chavez:Bayer: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Verastem: Consultancy; Pfizer: Consultancy. Hill:Beigene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Maddocks:Pharmacyclics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; OncLive: Honoraria. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Janssen Scientific: Consultancy, Other; Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; NCI: Research Funding. Portell:Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Takeda: Research Funding; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau. Castillo:TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding.

SummaryAlthough new multiple myeloma (MM) therapies are effective in alleviating some disease‐associated symptoms (e.g. bone pain, fatigue, functional decline), they can result in additional toxicities, further impacting health‐related quality of life (HRQoL). Here, we compared HRQoL and safety of lenalidomide‐bortezomib‐dexamethasone [RVd (n = 445)], bortezomib‐melphalan‐prednisone [VMP (n = 77)] and Vd or VMP (n = 588) in patients with newly diagnosed MM (NDMM) from the Connect® MM Registry, a large, USA, multicentre, prospective observational cohort study. Functional Assessment of Cancer Therapy‐Multiple Myeloma subscale, EuroQol‐5D overall score and Bone Pain Inventory HRQoL scores were significantly improved with RVd versus Vd/VMP. Serious adverse event rates were similar in all groups. Treatment with RVd maintained HRQoL in this real‐world, largely community‐based population of patients with NDMM.

AbstractIntroductionThe proximal humerus is a common site of primary and metastatic disease in the upper extremity. Historically, the goal of a hemiarthroplasty reconstruction was to provide a stable platform for hand and elbow function, with limited shoulder function. Techniques utilizing a reverse endoprosthesis (endoprosthetic replacement [EPR]) and allograft‐prosthetic composite (APC) have been developed; however, there is a paucity of comparative studies.MethodsA total of 83 (42 females, 41 males) patients undergoing an intraarticular resection of the humerus were reviewed. Reconstructions included 30 reverse and 53 hemiarthroplasty; including hemiarthroplasty EPR (n = 36) and APC (n = 17), and reverse EPR (n = 20) and APC (n = 10).ResultsReverse reconstructions had improved forward elevation (85° vs. 44°, p < .001) and external rotation (30° vs. 21°; p < .001) versus a hemiarthroplasty. Reverse reconstructions had improved American Shoulder and Elbow Surgeons scores (65 vs. 57; p = .01) and Musculoskeletal Tumor Society 93 scores (72 vs. 63; p < .001) versus hemiarthroplasty. Subluxation of the reconstruction was a common (n = 23, 27%), only occurring in hemiarthroplasty patients (EPR [n = 13, 36%] and APC [n = 10, 59%]).ConclusionThe current series highlights the improved functional outcome in patients undergoing reconstruction with a reverse arthroplasty compared to the traditional hemiarthroplasty. Currently reverse shoulder arthroplasty (APC or EPR) is our preferred methods of reconstruction in this patient population.

Background. A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way. Methods. The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2–2.5 L/min and 28–30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support. Results. Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment. Conclusions. These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.

Study Design: Retrospective database review. Objectives: The incidence and risk factors for surgical delay of multilevel spine fusion for adult spinal deformity (ASD), and the complications corresponding therewith, remain unknown. The objectives of this study are to assess the incidence and risk factors for unexpected delay of elective multilevel spinal fusions on the date of surgery as well as the postoperative complications associated with these delays. Methods: We conducted a retrospective review of the ACS-NSQIP database on patients undergoing elective spinal instrumentation of greater than 7 levels for ASD between the years 2005 and 2015. Preoperative risk factors for delay and postoperative complications were compared between the cohorts of patients with and without surgical delays. Results: Multivariate analysis of 1570 (15.6%) patients identified advanced age, male sex, American Society of Anesthesiologists (ASA) Class 4, and history of smoking as independent risk factors for delay. Patients experiencing surgical delay demonstrated longer operative times, increased intraoperative bleeding, longer hospitalizations, and significantly higher rates of postoperative complications. Patients experiencing delay demonstrated an almost 7-fold increase in mortality rate (3.4% vs 0.5%, P < .001). Conclusions: Delays in elective surgical care for spinal deformity are negatively related to patient outcomes. Advanced age, male sex, increased ASA class, and a history of smoking cigarettes place patients at risk for surgical delay of multilevel spinal fusion. Patients experiencing surgical delay are at higher risk for postoperative complications, including a 7-fold increase in mortality. These findings suggest that ASD surgery should be postponed in patients experiencing a delay, until modifiable risk factors can be medically optimized, and perhaps postponed indefinitely in those with nonmodifiable risk factors.

Abstract Background Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. Methods The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Results Of 9719 eligible women with hormone receptor–positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Conclusions Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.

Abstract Aim Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. Methods This is a multi‐institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan–Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. Results Two‐hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% ( n = 115/180) of women remained recurrence free at median follow‐up of 14.6 months (IQR, 3–37). In unadjusted analysis, recurrence‐free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. Conclusion This retrospective multi‐institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.