Citations

Abstract Introduction: Patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) who cannot tolerate or who are not eligible for autologous or chimeric antigen receptor T cell (CAR-T) therapy have limited therapeutic options and suboptimal long-term outcomes. In patients who were not eligible for HSCT, the rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) regimen (and variations using methylprednisolone or carboplatin/oxaliplatin) have shown an overall response rates (ORR) of ~50%, a complete response (CR) rate of ~25% (Gopal, Leuk Lymphoma, 2010), and a median progression-free survival (PFS) and an overall survival (OS) of 3 and 9 months, respectively (Crump, Hematol Oncol Clin N Am. 2016; Gopal Leuk Lymphoma, 2010; Ng, Br J Cancer, 2005; Sirohi, Hematology, 2007; Barton, Eur J Haematol. 2015; Moccia Leuk Lymphoma, 2017). Selinexor is an oral small molecule selective inhibitor of exportin-1 (XPO1) mediated nuclear export (SINE) compound leading to activation of tumor suppressor proteins and reduction in oncoprotein levels. It also reduces the expression of deoxyribonucleic acid (DNA) damage repair proteins and therefore potentiates DNA damage-based therapies leading to an increased death of cancer cells. Selinexor has synergistic effects with gemcitabine and cisplatin, and enhanced anti-lymphoma effects with dexamethasone. In the SADAL study (n=134), single-agent oral selinexor 60 mg twice weekly induced an ORR of 29% and a CR rate of 13% in patients with RR DLBCL. The response rates were consistent across various subgroups including patients <70 vs ≥70 years old, those with de novo and transformed DLBCL, and GCB and non-GCB subtypes of DLBCL. The median duration of response (DOR) was 9.3 months, and 23 months for patients who achieved CR. OS was 9.0 months. In June 2020, selinexor monotherapy was approved in the US for the treatment of adult patients with RR DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor in combination with R-GDP was evaluated in a Phase 1 clinical trial (SELINDA), in which patients with DLBCL received either 40 or 60 mg selinexor once or twice weekly in combination with standard dose R-GDP. The recommended phase 2 dose for further exploration was 40 or 60 mg once weekly with an ORR of 60-80%. Therefore, combining selinexor with R-GDP is expected to improve response rates, and continuation of treatment with single-agent selinexor is expected to prolong the duration of responses, improve PFS (and potentially OS) in patients with RR DLBCL. Materials and methods: XPORT-DLBCL-030 is a Phase 2/3, multicenter study. The Phase 2 portion of the study is an open-label randomized study to identify the optimal dose of selinexor (40 or 60 mg) in combination with R-GDP in patients (n=120) with RR DLBCL. Patients ≥18 years with 1-3 prior lines of therapy and ECOG performance status ≤2 who are not intended for HSCT or CAR-T therapy are randomized 1:1:1 to one of 3 treatment arms: Arm 1: selinexor 40 mg+R-GDP (S40+R-GDP); Arm 2: selinexor 60 mg+R-GDP (S60 + R-GDP); Arm 3: R-GDP. Combination treatment will be given for up to 6 cycles (21 days/cycle). After completing the SR-GDP combination therapy (EoC), patients in Arms 1 and 2 who reach at least partial response (PR), will receive weekly single-agent selinexor 60 mg (28 days/cycle) as "continuous therapy" until disease progression (PD) or unacceptable toxicity. After PD, patients will be followed up for survival. Patients in the R-GDP arm will be followed up for PD and survival. Patients who are ineligible for HSCT due to an active disease, or those who have primary refractory DLBCL, defined as no response or relapse within 6 months after ending first-line treatment, will be allowed to enroll in the study (up to 15% and 25%, respectively of all patients enrolled). The primary endpoint of the study is ORR according to the Lugano 2014 criteria. Secondary endpoints include PFS, OS, ORR-EoC, DOR and incidence and severity of adverse events. Figure 1 Figure 1. Disclosures Pinto: Takeda: Consultancy; MSD: Honoraria; Incyte: Honoraria; Roche: Honoraria, Speakers Bureau; Bristol Myers Squibb-CELGENE: Honoraria. Yimer: Texas Oncology: Current Employment; Pharmacyclics: Speakers Bureau; Amgen: Speakers Bureau; Sanofi: Speakers Bureau; GSK: Speakers Bureau; Beigene: Speakers Bureau; Janssen: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau. Manda: Morphosys: Honoraria; Genmab: Current equity holder in publicly-traded company. Canales: Sanofi: Consultancy; Incyte: Consultancy; Novartis: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; iQone: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria; Eusa Pharma: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria. Jurczak: European Medicines Agency, Sandoz-Novartis, Janssen China R&D, BeiGene, Epizyme, Acerta, AstraZeneca: Consultancy; AbbVie, AstraZeneca, Bayer, BeiGene, Celtrion, Celgene, Debbiopharm, Epizyme, Incyte, Janssen, Loxo Oncology, Merck, Mei Pharma, Morphosys, Novo Nordisk, Roche, Sandoz, Takeda, TG Therapeutics, Pharmacyclics, Affirmed, Gilead Sciences, Nordic Nanovecto: Research Funding; Jagiellonian University: Ended employment in the past 24 months; Maria Sklodowska-Curie National Research Institute of Oncology: Current Employment; AstraZeneca, BeiGene, Janssen, Loxo Oncology, Sandoz, Roche: Membership on an entity's Board of Directors or advisory committees. Sureda: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau. Ma: Karyopharm Therapeutics Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Li: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Ingalls: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Arriola: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Arazy: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: CD19 CAR T cell therapies have demonstrated high initial complete remission (CR) rates of 70-80% in relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with durable remissions observed in a subset of patients. Despite the remarkable initial CR rate, relapses occur in 20-45% of patients and with increasing use of CD19 CAR T cell therapies in ALL, a key remaining clinical question is the role of post-CAR HCT. Methods: Patients up to 26 years treated with the commercial (i.e., tisagenlecleucel) or investigational CD19 CAR T cell products from 2014 to 2019 in the United States were included. The objectives were to examine the impact of post-CAR HCT on mortality, disease-free survival (DFS), leukemia relapse, GVHD and transplant related mortality among HCT recipients. The intent of HCT was analyzed as consolidation when there was no evidence of post-CAR T cell relapse prior to HCT. Cox regression multivariable analysis used HCT as time-dependent variable along with age, performance status and time from diagnosis to CAR-T cell infusion to evaluate its impact on outcomes. Results: We identified 347 patients who received CD19 CAR T cells from 86 centers. Median age was 13 (range, 0.4-26 years) with 39% of patients from Hispanic or Latino ethnic origin. Patients were high risk and heavily pretreated; 56% had poor cytogenetics, 51% had ≥3 line of prior therapies and 34% had prior HCT. Most of the patients (74%) received tisagenlecleucel. Disease burden at the time of CAR T cell infusion included morphologic disease (≥5% bone marrow blasts) (65%), measurable residual disease (MRD) positive (16%) and negative CR (18%). CRS of all grades was observed in 57.6% and grade 3-4 CRS in 13%; neurotoxicity of all grades was observed in 25% and grade 3-4 in 8%. With a median follow-up of 12.7 months (range, 2.2-60.3), DFS at 3, 6 and 12 months following CAR T cell infusion was 80.9% % (95% CI: 76.6%-84.9%), 71.2% (95% CI: 66.1%-76.0%) and 57.6% (95% CI: 51.8%-63.3%), respectively. OS at 3, 6 and 12 months was 93.6% (95% CI: 90.8%-96.0%), 89.8% (95% CI: 86.4%-92.8%) and 79.4% (95% CI: 74.7%-83.6%), respectively. Incidences of relapse without censoring at subsequent HCT at month 3, 6 and 12 were 18.5% (95% CI: 14.5%-22.8%), 28.2% (95% CI: 23.5%-33.3%), and 40.6% (95% CI: 35.0%-46.3%), respectively. Of the 347 patients who received CD19 CAR therapy, 62 patients (18%) had subsequent HCT in CR as a consolidation post-CAR with a median time from CAR T to HCT of 4.7 months (range, 1.1-18.6). 36% had a prior HCT (i.e., pre-CAR), 87% received myeloablative regimen and among the 57 patients with MRD evaluation 56 were negative (98%). Frequencies of post-CAR HCT did not change during the 5-year study period. Overall, transplant related mortality (TRM) at month 6 was 8.9% (95% CI: 3.6-16.1), and grade 2-4 acute GvHD was observed in 38.0% (95% CI: 28.4-48.2) of patients at month 6. Post-CAR HCT used as a consolidation was associated with lower relapse (hazard ratio (HR) 0.37; p=0.037) but no significant impact on mortality (HR 0.75, p=0.51) or DFS (HR=0.46, p=0.057). When accounting for any HCT performed after CAR T cell, HCT was associated with higher mortality (Figure). Conclusions: This is the largest clinical series to date examining the impact of post-CAR HCT on clinical outcome of R/R B-ALL patients. We found that 18% of the patients had post-CAR HCT as a consolidation therapy with a favorable safety profile of 8.9% TRM rate despite a prior transplant rate of 36%. Consolidation HCT after CAR T cell resulted in significant reduction in leukemia relapse with a trend towards better DFS. Consolidation HCT seem safe and incurred a benefit by reducing disease relapse. Further studies in understanding the role of consolidation HCT as planned, or post-CAR T cell response-based strategy or treatment for early B-cell recovery are needed to further define the best candidates for HCT after tisagenlecleucel . Figure 1 Figure 1. Disclosures Park: BMS: Consultancy; Affyimmune: Consultancy; Kite Pharma: Consultancy; Curocel: Consultancy; Novartis: Consultancy; Minerva: Consultancy; Innate Pharma: Consultancy; PrecisionBio: Consultancy; Intellia: Consultancy; Amgen: Consultancy; Autolus: Consultancy; Servier: Consultancy; Artiva: Consultancy; Kura Oncology: Consultancy. Nikiforow: Kite/Gilead: Other: ad HOC Advisory Boards; Novartis: Other: ad Hoc Advisory Boards; Iovance: Other: ad Hoc Advisory Boards; Glaxo Smith Kline (GSK): Other: ad Hoc Advisory Boards. Hu: Kite/Gilead: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Ahmed: Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding; Xencor: Research Funding. Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees. Cairo: Servier: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Jazz Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees; Nektar: Membership on an entity's Board of Directors or advisory committees. Dholaria: Janssen: Research Funding; Takeda: Research Funding; Jazz: Speakers Bureau; MEI: Research Funding; Pfizer: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; Celgene: Speakers Bureau. Grover: Kite: Other: Advisory Board; Genentech: Research Funding; ADC: Other: Advisory Board; Tessa: Consultancy; Novartis: Consultancy. Locke: Gerson Lehrman Group: Consultancy; Emerging Therapy Solutions: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Calibr: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; Novartis: Consultancy, Other, Research Funding; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Takeda: Consultancy, Other; EcoR1: Consultancy; Cowen: Consultancy; Umoja: Consultancy, Other; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding. Murthy: CRISPR Therapeutics: Research Funding. Mussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Pulsipher: Jasper Therapeutics: Honoraria; Adaptive: Research Funding; Equillium: Membership on an entity's Board of Directors or advisory committees. Qayed: Novartis: Membership on an entity's Board of Directors or advisory committees; Medexus: Membership on an entity's Board of Directors or advisory committees; Mesoblast: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; BMS: Other. Reshef: Gilead, BMS, Precision, Immatics, Atara, Takeda, Shire, Pharmacyclics, Incyte: Research Funding; Gilead and Novartis: Honoraria; Bayer, BMS, Regeneron, TScan, Synthekine, Atara, Jasper: Consultancy. Rizzieri: Kite: Honoraria, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acrotech: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria; Pharmacyclics: Honoraria. Sharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Medexus Inc: Consultancy; CRISPR Therapeutics: Other, Research Funding; Vindico Medical Education: Honoraria; Spotlight Therapeutics: Consultancy; Novartis: Other: Salary support paid to institution. Schultz: BMS DSMB: Other: payment; Sobi: Membership on an entity's Board of Directors or advisory committees. Turtle: Century Therapeutics Ad hoc advisory boards (last 12 months): Nektar Therapeutics, Allogene, PACT Pharma, Astra Zeneca, Amgen: Membership on an entity's Board of Directors or advisory committees; Precision Biosciences: Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Membership on an entity's Board of Directors or advisory committees; Caribou Biosciences: Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees; ArsenalBio: Membership on an entity's Board of Directors or advisory committees; Minerva: Other; Nektar Therapeutics: Other; Juno Therapeutics/BMS: Other: Payments, Patents & Royalties: Patent licensed to Juno Therapeutics.; Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, Myeloid Therapeutics, ArsenalBio: Current holder of stock options in a privately-held company. Pasquini: Kite Pharma: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Research Funding. Perales: MorphoSys: Honoraria; Cidara: Honoraria; Bristol-Myers Squibb: Honoraria; Miltenyi Biotec: Honoraria, Other; Sellas Life Sciences: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Omeros: Honoraria; Nektar Therapeutics: Honoraria, Other; Equilium: Honoraria; Novartis: Honoraria, Other; NexImmune: Honoraria; Incyte: Honoraria, Other; Kite/Gilead: Honoraria, Other; Merck: Honoraria; Servier: Honoraria; Medigene: Honoraria.

Abstract Introduction: Patients with coronavirus disease 2019 (COVID-19) have an increased risk for venous thromboembolic events. Thrombotic events contribute to the morbidity and mortality associated with COVID-19 infection, and have prompted investigation into strategies for mitigating thrombosis risk in patients hospitalized with COVID-19 infection. Our team reviewed the charts of patients hospitalized with COVID-19 pneumonia at a tertiary hospital in metropolitan Phoenix Arizona between 2020-2021, to assess frequency and efficacy of utilizing a VTE prophylaxis algorithm designed to prevent thrombosis in patients infected with COVID-19. Methods: A total of 846 patients were retrospectively evaluated to determine if they were treated with guideline-appropriate anticoagulation while hospitalized with COVID-19, as well as if they developed venous or arterial thrombotic events, or major or minor bleeds. 317 patients were excluded for taking therapeutic anticoagulation prior to admission, or for having a COVID-19 diagnosis >7 days after admission. Appropriate anticoagulation was determined by an institutionally designed COVID-19 thromboprophylaxis algorithm, based on platelet count, d-dimer, bleeding risk, and level of medical care required. Regimen options included: no anticoagulation, prophylactic enoxaparin (40 mg SQ daily) or heparin in the setting of kidney dysfunction, weight-based dosing of enoxaparin (40 mg SQ BID if BMI>40), intermediate intensity enoxaparin without thrombus (30 mg BID if BMI<40, or 40 mg BID if BMI>40), and therapeutic anticoagulation (for example enoxaparin 1 mg/kg BID) with thrombus. Demographics: Demographic data and clinical characteristics were collected for 529 patients. Average age was 59 years old, and the majority were men (58.4%). Most patients were White (58.3%), followed by Hispanic (17.8%), or Native American (15.7%). Fewer patients had a normal BMI (21.3%; BMI 18.5 - 24.9) compared to those who were overweight (31.2%; BMI 25-29.9) or obese (43.1% BMI > 30). Other comorbidities included Type 1 or Type 2 diabetes mellitus (N= 172, 32.5%), hypertension (N = 271, 51.2%), and hyperlipidemia (N = 176, 33.3%). Results: A total of 42 patients (8%), were diagnosed with a venous thrombosis during hospitalization. Patients admitted to the ICU were significantly more likely to have a thrombotic event of any type compared to non-ICU patients (21.6% to 5.7%; p < 0.001). Specifically, critically ill patients had higher incidences of deep vein thrombosis (9.5% to 0.7%), pulmonary emboli (8.1% to 4.8%), and superficial thrombi (2.7% to 0.2%). Only 1.1% of patients (6/529) experienced any bleeding, of which 3 were classified as a major bleed. Discussion: Among patients hospitalized at our institution with COVID-19, the majority were anticoagulated appropriately according to the COVID-19 thromboprophylaxis algorithm. Overall incidence of thrombosis in the study population was 8%. A significantly higher percent of critically ill patients had thrombi, supporting reports of correlation between severity of illness and thrombosis risk. The two regimens of anticoagulation least adhered to were weight-based and intermediate-based dosing, likely reflecting a departure from the hospital's thromboprophylaxis regimens prior to COVID-19 pandemic. Further studies are needed to characterize whether identifiable risk factors correlate with the incidence of thrombosis, and whether treatment with lower than recommended doses of anticoagulation, based on the COVID-19 thromboprophylaxis algorithm, were associated with thrombosis. Disclosures No relevant conflicts of interest to declare.

Abstract INTRODUCTION Central nervous system (CNS) relapse is a challenging situation in diffuse large B-cell lymphoma (DLBCL). High CNS-International Prognostic Index (IPI), activated B-cell (ABC) subtype and MYD88 L265P mutation, features often found in transformed Waldenström macroglobulinemia (WM), are associated with a higher risk for developing CNS relapse. This study was aimed to describe CNS involvement in a large cohort of transformed WM. METHODS This international multicenter retrospective study included patients with a diagnosis of WM and a concurrent or sequential histological diagnosis of DLBCL. CNS disease was diagnosed by detection of DLBCL cells in the cerebrospinal fluid and/or by brain biopsy. Patients with CNS involvement by lymphoplasmacytic cells (Bing-Neel syndrome) were excluded. Of 254 identified patients with a diagnosis of histological transformation (HT) between 1988 and 2020, 19 were excluded due to lack of data on extranodal involvement. The first part of the analysis focused on baseline CNS involvement. Clinicobiological characteristics were compared between groups using Chi-square or Fisher's exact tests or Mann Whitney tests as appropriate. We analyzed CNS recurrence in the second part of the study. Forty-eight additional patients were excluded due to baseline CNS involvement (n = 25), absence of treatment at HT (n = 14) and lack of details on follow-up (n = 9). Cumulative incidence of CNS relapse was analyzed using competing-risk models that accounted for other events like systemic relapse or death from any cause, reporting sub-hazard ratio (SHR). RESULTS Baseline CNS involvement was present in 25 patients (11%) with transformed WM, including 10 (4%) with parenchymal disease, 10 with leptomeningeal, 4 (2%) with both, and 1 with unspecified CNS involvement. Characteristics associated with baseline CNS involvement were performance status 2-4 (P=0.03) and ≥2 extranodal sites (P=0.02). Median survival after HT was 1 year [0.7-2.5], comparable to the one of patients without CNS disease (1.8 year [1.2-2.6], P=0.74). We observed no difference in survival based on isolated CNS involvement (n = 10) compared to CNS and systemic involvement (n = 15) (P=0.94). Twenty-three CNS relapses occurred (12%). The 2-year and 3-year rates of CNS relapse were 9% (95% CI, 6-14) and 11% (95% CI, 7-16) (Figure 1). The median time to relapse in the CNS was 11 months (95% CI, 7-25). Thirteen CNS recurrences (57%) occurred during the first year of follow-up. Seventy percent were isolated CNS relapses. The location was leptomeningeal in 43% of cases, parenchymal in 35%, both in 17%, and unspecified in 4%. According to CNS-IPI risk groups (data available for 20 patients), 9 patients (45%) belonged to the high-risk group, 10 (50%) to the intermediate-risk group and 1 (5%) to the low-risk group. Prior to CNS relapse, 87% of patients had received rituximab, and 39% had received CNS prophylaxis (30% intrathecal chemotherapy, 4% high-dose methotrexate (HD-MTX), and 4% both). After CNS recurrence, 96% of patients received salvage treatment: combination of HD-MTX and HD-cytarabine (48%), HD-MTX alone (30%), or HD-cytarabine alone (9%). Four patients underwent consolidative autologous stem cell transplantation. The median survival after CNS relapse was 5.6 months. Factors associated with 3-year cumulative incidence of CNS recurrence in univariate analysis were involvement of kidney/adrenal glands (HR, 4.4; P=0.01) and MYD88 L265P mutation (P=0.01) (Figure 2A and B). Of note, among 74 patients (over 187, 40%) with data available for MYD88 mutation status, 11 CNS relapses occurred in patients with MYD88 L265P mutation (n = 54, 20%) whereas no relapse were observed in MYD88 WT cohort (n = 20). A trend toward higher risk of CNS relapse for ≥2 extranodal sites (HR, 2.3, 95% CI 0.98-5.3; P=0.06) was observed. Cumulative incidence according to CNS-IPI risk groups (0% in the low-risk, 9% in the intermediate-risk and 14% in the high-risk group) was not statistically significant (P=0.47). CONCLUSION CNS involvement occurs frequently in transformed WM. Rate of CNS relapse seems similar to DLBCL patients belonged to the CNS-IPI high-risk group. Special attention should be paid to patients with kidney/adrenal involvement and MYD88 L265P mutation. Figure 1 Figure 1. Disclosures Vos: Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel reimbursement. Treon: X4: Research Funding; Janssen: Consultancy, Research Funding; Dana Farber Cancer Institute: Current Employment; BMS: Consultancy, Research Funding; Self: Patents & Royalties: Holder of multiple patents related to testing and treatment of MYD88 and CXCR4 mutated B-cell malignancies; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Dimopoulos: Janssen: Honoraria; Beigene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Takeda: Honoraria. Kapoor: Cellectar: Consultancy; Karyopharm: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Background Fetal posterior cerebral artery (FPCA) occlusion is a rare but potentially disabling cause of stroke. While endovascular treatment is established for acute large vessel occlusion stroke, FPCA occlusions were excluded from acute ischemic stroke trials. We aim to report the feasibility, safety, and outcome of mechanical thrombectomy in acute FPCA occlusions. Methods We performed a multicenter retrospective review of consecutive patients who underwent mechanical thrombectomy of acute FPCA occlusion. Primary FPCA occlusion was defined as an occlusion that was identified on the pre‐procedure computed tomography angiography or baseline angiogram whereas a secondary FPCA occlusion was defined as an occlusion that occurred secondary to embolization to a new territory after recanalization of a different large vessel occlusion. Demographics, clinical presentation, imaging findings, endovascular treatment, and outcome were reviewed. Results There were 25 patients with acute FPCA occlusion who underwent mechanical thrombectomy, distributed across 14 centers. Median National Institutes of Health Stroke Scale on presentation was 16. There were 76% (19/25) of patients who presented with primary FPCA occlusion and 24% (6/25) of patients who had a secondary FPCA occlusion. The configuration of the FPCA was full in 64% patients and partial or “fetal‐type” in 36% of patients. FPCA occlusion was missed on initial computed tomography angiography in 21% of patients with primary FPCA occlusion (4/19). The site of occlusion was posterior communicating artery in 52%, P2 segment in 40% and P3 in 8% of patients. Thrombolysis in cerebral infarction 2b/3 reperfusion was achieved in 96% of FPCA patients. There were no intraprocedural complications. At 90 days, 48% (12/25) were functionally independent as defined by modified Rankin scale≤2. Conclusions Endovascular treatment of acute FPCA occlusion is safe and technically feasible. A high index of suspicion is important to detect occlusion of the FPCA in patients presenting with anterior circulation stroke syndrome and patent anterior circulation. Novelty and significance This is the first multicenter study showing that thrombectomy of FPCA occlusion is feasible and safe.

Meniscus injury and meniscectomy are strongly related to osteoarthritis, thus there is a clinical need for meniscus replacement. The purpose of this study is to create a meniscus scaffold with micro-scale circumferential and radial fibres suitable for a one-stage cell-based treatment. Poly-caprolactone-based scaffolds with three different architectures were made using melt electrowriting (MEW) technology and their in vitro performance was compared with scaffolds made using fused-deposition modelling (FDM) and with the clinically used Collagen Meniscus Implants® (CMI®). The scaffolds were seeded with meniscus and mesenchymal stromal cells (MSCs) in fibrin gel and cultured for 28 d. A basal level of proteoglycan production was demonstrated in MEW scaffolds, the CMI®, and fibrin gel control, yet within the FDM scaffolds less proteoglycan production was observed. Compressive properties were assessed under uniaxial confined compression after 1 and 28 d of culture. The MEW scaffolds showed a higher Young’s modulus when compared to the CMI® scaffolds and a higher yield point compared to FDM scaffolds. This study demonstrates the feasibility of creating a wedge-shaped meniscus scaffold with MEW using medical-grade materials and seeding the scaffold with a clinically-feasible cell number and -type for potential translation as a one-stage treatment.