Abstract: Introduction. Ibrutinib is a first-in-class, oral, once-a-day Bruton's tyrosine kinase inhibitor that achieves high overall response rates and durable remissions in patients with chronic lymphocytic leukemia (CLL) including those with high-risk features (unmutated IGHV, TP53 abnormalities, 11q deletion). Survival with continuous single-agent ibrutinib in previously-untreated CLL patients is comparable to an age-matched general population (Figure 1). IBRORS is an observational, retrospective, multicentre study to describe the characteristics and clinical outcomes of patients with CLL treated with single-agent ibrutinib in routine clinical practice in Spain. This present analysis reviews the subset of patients in IBRORS who received ibrutinib as the first-line of treatment. This series includes a significant number of patients with high risk cytogenetic/molecular alterations (del17p/TP53 M), which corresponds with the approved indication for first-line CLL patients in Spain at the time. Methods. Adult patients diagnosed with CLL treated with single-agent ibrutinib in first-line, or at first or second relapse since its commercialization in Spain (between January 2016 to January 2019) were included in the IBRORS study. Clinical characteristics of patients, efficacy and tolerability of ibrutinib as first-line treatment were analyzed here. A Kaplan-Meier analysis was performed for overall survival (OS) and progression-free survival (PFS). Results. 84 patients, from a total of 269 included in IBRORS, received single-agent ibrutinib as first-line treatment. The median age was 71.3 years (range 63-77) at the time of ibrutinib initiation. 56.3% of patients presented with an intermediate/high-risk Rai-Binet stage, and the majority of patients (98.6%) had an ECOG PS of 0-1. 91.7% of patients had at least 1 high risk molecular cytogenetic factor (unmutated IGHV, TP53 abnormalities, 11q deletion or complex karyotype) described in table 1. Baseline comorbidities of patients are described in table 2. Concomitant medication included anticoagulants (9.5% patients; vitamin K antagonist [n=4], Apixaban [n=1] and LMWH [n=3] patients), antiplatelet agents (11.9% patients), and antihypertensives (50% patients). The overall response rate (ORR) was 79.5%; 14/84 (16.6%) achieved a complete response (CR), 14/84 (16.6%) achieved CR unconfirmed, 27/84 (32.14%) achieved a partial response (PR) and 12/84 (14.2%) a PR + lymphocytosis. The median PFS and OS were not reached, and the estimated PFS at 24 months was 84.5% (73.4-95.6%). OS and PFS curves are represented in figure 2. The PFS of each patient subgroup with high-risk cytogenetic characteristics was similar to that of all patients in the first-line cohort: del17p/TP53 mutation (HR = 0.963 [95% CI 0.188-4.928]; p = 0.964), del11q (HR = 0.042 [95% CI 0.000-682.736] ; p=0.521), unmutated IGHV (HR = 0.391 [95% CI 0.110-1.394]; p = 0.148). The median duration of exposure to ibrutinib was 17.3 (11.9-25.6) months. Dose reduction of ibrutinib occurred in 17/84 (20.2%) patients, 8/84 (9.52%) due to toxicity (4 hematologic toxicity and 4 non-hematologic toxicity). 27/84 (32.1%) patients had temporary interruption of treatment. 15/84 (17.8%) patients permanently discontinued ibrutinib including 6 (7.14%) patients due to progression, 4 (4.76%) due to toxicity and 5 for other reasons. Safety: 49/84 (58.3%) patients developed at least one adverse event (AE), while 12/84 (14.2%) patients developed at least one serious adverse event (SAE). Twelve (14.3%) patients reported at least one haematological toxicity while 53 patients (63.1%) recorded at least one non-haematological toxicity. Only 1 patient experienced grade 3 atrial fibrillation, which did not lead to discontinuation. The most common AEs are described in table 3. Conclusion. This population of previously-untreated CLL patients, enriched for high-risk genomic features, reflects the initial approval of ibrutinib for the treatment of first-line patients with del17p in Spain. Single-agent Ibrutinib as the first-line treatment in this real world population was effective regardless of risk factors and well tolerated, with a low rate of discontinuation due to toxicity. Findings are consistent with those reported in clinical trials. Disclosures Loscertales: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria. Arguiñano:AbbVie: Honoraria; Janssen: Honoraria; BMS-Celgene: Honoraria; Novartis: Honoraria. Hernandez-Rivas:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Pérez Persona:Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Jannsen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Takeda: Consultancy. Loriente:Janssen Cilag: Current Employment. Villanueva:Janssen Cilag: Current Employment.

Abstract: Introduction. The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Chimeric antigen receptor (CAR) T-cell therapy is approved for R/R DLBCL (≥3 rd line) in Spain since April 2019, based on data from single-arm phase 2 trials that showed complete response (CR) rates between 40-50% and prolonged remissions in 30-40% of patients. Real-world (RW) data from different countries have shown similar efficacy to pivotal trials, but there are no studies focused on the global Spanish experience, including different constructs with a large number of patients and no comparative studies have been carried out in Spain between commercial CAR-T therapy and the standard treatment of the pre-CAR era. Methods This is a multicenter, retrospective, observational study that included all patients with R/R DLBCL treated with CAR-T therapy who were registered in the GELTAMO/GETH database of patients treated with CAR-T therapy in Spain (n=255). The main objective was to analyze efficacy in terms of response rates and survival and analyze prognostic factors influencing survival. In addition, this cohort was compared with a historical population of R/R DLBCL patients from the GELTAMO-IPI study (Montalbán et al, Br J Haematol 2017), treated in the pre-CAR era (n = 158). From both cohorts, refractory patients according to the Scholar-1 criteria (primary refractoriness, refractoriness to last treatment, or early relapse after autologous stem-cell transplant) were identified and included in the comparative analysis. Results Characteristics of the CAR-T group at diagnosis and at infusion are shown in Table 1. From the 255 patients registered, 13 were excluded due to absence of follow up data and 4 for mantle cell lymphoma histology. Finally, 238 patients were included in the intention-to-treat analysis and 226 received the CAR-T infusion (124 axicabtagene ciloleucel, 101 tisagenlecleucel and 1 lisocabtagenemaraleucel). Median time from official approval to infusion was 60 days (34-363), and median time from apheresis to infusion was 46 days (16-349). Regarding adverse events of special interest, 79% of patients had cytokine release syndrome (7% ≥ grade 3), and 32% of patients had neurotoxicity (13.7% ≥ grade 3). Best response rates after CAR-T infusion were: CR 42%, partial response (PR) 27%, stable disease (SD) 7% and progressive disease (PD) 24%. With a median follow up from infusion of 8 months, median progression-free survival (PFS) was 3.5 months (95% CI: 1.9-5), and median overall survival (OS) was not reached, with a 12-month OS of 53% (95% CI: 45-62); 12-month OS and PFS for patients who achieved CR was 86% (Figure 1) and 78% respectively. Factors influencing PFS and OS in the univariate analysis are shown in table 2. In the multivariate analysis, the factors with independent influence on both PFS and OS were R-IPI and Eastern Cooperative Oncology Group-Performance status (ECOG-PS) pre-CAR, and presence of refractory disease to last treatment, as shown in table 3. Regarding the comparative analysis with the historical cohort, the groups were well balanced, except for age and median follow up (Table 4). The survival for this analysis was calculated since the failure to last treatment. Patients treated with CAR T-cells vs standard of care pre-CAR had significantly better PFS (median of 7.9 vs 5.7 months, p=0.002), and OS (median of 16 vs 9.2, p & lt;0.001). Conclusions: We conclude that efficacy results obtained from RW CAR T-cell therapy in Spain are comparable to the pivotal trials. The results of the comparative analysis suggest that the efficacy of CAR-T therapy in refractory patients is superior to that of the treatments available in the pre-CAR era. Figure 1 Figure 1. Disclosures Bastos-Oreiro: F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau. Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Corral: Gilead: Consultancy; Novartis: Consultancy; Gileqd: Honoraria. Terol: Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Roche: Consultancy; Hospital Clinico Valencia: Current Employment; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; BMS: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Mussetti: Gilead: Other: Unspecified, Research Funding; Novartis: Honoraria, Other: Unspecified; Takeda: Honoraria. Luzardo Henriquez: Kyte/Gilead. Takeda. Roche: Honoraria. Sancho: F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees. Salar: Roche: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Gilead: Research Funding; Janssen: Consultancy, Speakers Bureau. Herrero: Novartis: Consultancy, Honoraria. Sureda: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Support for attending meetings and/or travel; 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; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Consultancy; GSK: Consultancy, Honoraria, Speakers Bureau; Janssen: 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; 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; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau. Barba: Novartis: Honoraria; BMS: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Gilead: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Gilead: Consultancy, Honoraria; Morphosys: Consultancy; Kyowa Kirin: Consultancy; Clinigen: Consultancy; Eusa Pharma: Consultancy; Novartis: Consultancy; Takeda: Honoraria; Incyte: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).

Abstract: 7505 Background: Pola-G-Len may enhance anti-tumor immune response in R/R FL. We report a pre-planned interim analysis of the safety/efficacy of induction and maintenance with Pola-G-Len in pts with R/R FL in a phase Ib/II study. Methods: Pts received induction treatment with 6x 28-D cycles of: G 1000mg IV (C1: D1, D8, D15; C2–6: D1); Pola 1.4mg/kg or 1.8mg/kg (dose escalation [DE]) or RP2D (expansion) IV (D1); and Len 10–20mg (DE) or RP2D (expansion) PO (D1–21). Pts with CR/PR/SD at the end of induction (EOI) received G 1000mg (D1 every 2mo, for 24mo), and Len (10mg, D1–21 monthly, 12mo). Primary endpoints: C1 DLTs, safety/tolerability, CR rate at EOI (modified Lugano criteria). Results: At the interim data cut-off (7/6/2018), 52 pts were enrolled: 9 discontinued the study (adverse events [AE] , n=3; death due to PD, n=4; pt withdrawal, n=1; other, n=1). Median pt age was 62 (range 32–87) years; 58% FLIPI 3–5; 79% ≥2 prior therapy lines; 50% refractory to last treatment. Grade ≥3 AEs were experienced by 75% of pts: neutropenia (46%), thrombocytopenia (17%), anemia (12%) and infections (12%) were most common. AEs leading to Len dose reduction/interruption occurred in 31%/52% of pts. One Grade 5 AE was reported (septic shock after PD in pt receiving subsequent therapy). RP2D: Pola 1.4mg/kg + Len 20mg. Preliminary efficacy data suggest high activity (Table). Median PFS not reached (median follow-up duration 8.95mo; efficacy-evaluable population [EEP]). Conclusions: The safety profile of Pola-G-Len is consistent with known profiles of the individual drugs. Response rates at EOI with Pola-G-Len are promising, with high CR compared with available R/R FL treatments. Responses at EOI (EEP; RP2D; N=18). Clinical trial information: NCT02600897. [Table: see text]

Abstract: The SRealCLL study aimed to obtain real-world evidence on the clinical characteristics and treatment patterns of patients with chronic lymphocytic leukemia (CLL) using natural language processing (NLP). Electronic health records (EHRs) from seven Spanish hospitals (January 2016–December 2018) were analyzed using EHRead® technology, based on NLP and machine learning. A total of 534 CLL patients were assessed. No treatment was detected in 270 (50.6%) patients (watch-and-wait, W & W). First-line (1L) treatment was identified in 230 (43.1%) patients and relapsed/refractory (2L) treatment was identified in 58 (10.9%). The median age ranged from 71 to 75 years, with a uniform male predominance (54.8–63.8%). The main comorbidities included hypertension (W & W: 35.6%; 1L: 38.3%; 2L: 39.7%), diabetes mellitus (W & W: 24.4%; 1L: 24.3%; 2L: 31%), cardiac arrhythmia (W & W: 16.7%; 1L: 17.8%; 2L: 17.2%), heart failure (W & W 16.3%, 1L 17.4%, 2L 17.2%), and dyslipidemia (W & W: 13.7%; 1L: 18.7%; 2L: 19.0%). The most common antineoplastic treatment was ibrutinib in 1L (64.8%) and 2L (62.1%), followed by bendamustine + rituximab (12.6%), obinutuzumab + chlorambucil (5.2%), rituximab + chlorambucil (4.8%), and idelalisib + rituximab (3.9%) in 1L and venetoclax (15.5%), idelalisib + rituximab (6.9%), bendamustine + rituximab (3.5%), and venetoclax + rituximab (3.5%) in 2L. This study expands the information available on patients with CLL in Spain, describing the diversity in patient characteristics and therapeutic approaches in clinical practice.

Abstract: Background: The current standard of care for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is R CHOP; however, approximately 40% of patients are not cured. The CD79b-targeting antibody-drug conjugate, polatuzumab vedotin, is approved in relapsed/refractory DLBCL in combination with bendamustine and rituximab, and has also demonstrated promising first line activity and safety when combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) in a Phase Ib/II study (Tilly, et al. Lancet Oncol 2019). Thus, in the Phase III POLARIX study (NCT03274492) we compared pola-R-CHP with R-CHOP in patients with previously untreated DLBCL. Methods: In this double-blind, placebo-controlled, international study, patients with previously untreated DLBCL and an International Prognostic Index (IPI) of 2-5 were randomized 1:1 to receive six cycles of pola-R-CHP (with a vincristine placebo) or R-CHOP (with a polatuzumab vedotin placebo); all patients also received two additional cycles of rituximab. Patients received polatuzumab vedotin 1.8mg/kg or vincristine 1.4mg/m² administered on Day 1, plus intravenous rituximab 375mg/m2, cyclophosphamide 750mg/m², doxorubicin 50mg/m², and placebo on Day 1, and oral prednisone 100mg once daily on Days 1-5. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included investigator-assessed event-free survival (EFS), independent review committee-assessed complete response (CR) rate at the end of treatment by positron emission tomography-computed tomography (PET-CT), disease-free survival (DFS), overall survival (OS), and safety. Results: Overall, 879 patients were randomized, 440 to pola-R-CHP and 439 to R-CHOP. Median age was 65 (range 19-80) years, and the majority of patients had IPI 3-5 (62.0%). At the data cut-off of June 28, 2021, and after a median follow-up of 28.2 months, PFS was superior with pola-R-CHP vs R CHOP (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57-0.95; P & lt;0.02). The 2-year PFS rate was 76.7% (95% CI: 72.7-80.8) with pola-R-CHP vs 70.2% (95% CI: 65.8-74.6) with R-CHOP. EFS favored pola-R-CHP compared with R-CHOP (HR 0.75; 95% CI: 0.58-0.96; P=0.02). The end-of-treatment PET-CT CR rate was not significantly different with pola-R-CHP vs R-CHOP (78.0% vs 74.0%; P=0.16); however, DFS suggested responses were more durable with pola-R-CHP than with R-CHOP (HR 0.70; 95% CI: 0.50-0.98). There was no difference in OS between treatment arms (HR 0.94; 95% CI: 0.65-1.37; P=0.75). At the time of data cut-off, 99 (23%) and 133 (30%) patients in the pola-R-CHP and R-CHOP arms, respectively, had received at least one subsequent anti-lymphoma therapy. Fewer patients in the pola-R-CHP than the R-CHOP arm received subsequent anti-lymphoma treatments (radiotherapy, 9.3% vs 13.0%; stem cell transplantation, 3.9% vs 7.1%; chimeric antigen receptor T-cell therapy, 2.0% vs 3.6%). The safety profile was comparable for pola-R-CHP vs R-CHOP, including rates of grade 3-4 adverse events (AEs; 57.7% vs 57.5%), serious AEs (34.0% vs 30.6%), grade 5 AEs (3.0% vs 2.3%), and AEs leading to dose reduction (9.2% vs 13.0%), respectively. The frequency and severity of peripheral neuropathy were similar for pola-R-CHP vs R-CHOP (any grade, 52.9% vs 53.9%; grade 3-4, 1.6% vs 1.1%). Conclusion: The pola-R-CHP combination demonstrated a 27% reduction in the relative risk of disease progression, relapse, or death compared with R-CHOP, with a similar safety profile in the first-line treatment of patients with DLBCL. Disclosures Tilly: Karyopharm: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Other: Meeting attendance and travel, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Morschhauser: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Genentech, Inc.: Consultancy; Janssen: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees. Sehn: Novartis: Consultancy; Genmab: Consultancy; Debiopharm: Consultancy; Teva: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; AbbVie: Consultancy; Acerta: Consultancy; Amgen: Consultancy; Apobiologix: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Kite: Consultancy; Karyopharm: Consultancy; Lundbeck: Consultancy; Merck: Consultancy; Morphosys: Consultancy; Sandoz: Consultancy; Seattle Genetics: Consultancy; Takeda: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy. Friedberg: Bayer: Membership on an entity's Board of Directors or advisory committees; Acerta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Trněný: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria. Sharman: AbbVie: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Bristol-Myers Squibb: Consultancy; Lilly: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; TG Therapeutics: Consultancy; Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Velos: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Herbaux: Takeda: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria; Janssen: Honoraria. Burke: Verastem: Consultancy; AstraZeneca: Consultancy; Morphosys: Consultancy; Adaptive Biotechnologies: Consultancy; Epizyme: Consultancy; Kura: Consultancy; AbbVie: Consultancy; BeiGene: Consultancy, Speakers Bureau; Kymera: Consultancy; Bristol-Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Speakers Bureau; Gilead: Consultancy; Genentech, Inc.: Consultancy. Matasar: Memorial Sloan Kettering Cancer Center: Current Employment; Merck Sharp & Dohme: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; IGM Biosciences: Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Rocket Medical: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Honoraria. Rai: Chugai Pharmaceutical Co., Ltd: Speakers Bureau; ONO Pharmaceutical Co., Ltd: Speakers Bureau; Janssen Pharmaceutical: Speakers Bureau; Eisai Co., Ltd: Speakers Bureau. Izutsu: AbbVie: Honoraria; Allergan Japan: Honoraria; AstraZeneca: Honoraria, Research Funding; Bayer: Research Funding; BeiGene: Research Funding; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Fuji Film Toyama Chemical: Honoraria; Genmab: Honoraria, Research Funding; Huya Biosciences: Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; MSD: Research Funding; Novartis: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Pfizer: Research Funding; Solasia: Research Funding; Symbio: Honoraria; Takeda: Honoraria, Research Funding; Yakult: Research Funding. Mehta-Shah: C4 Therapeutics: Consultancy; Kiowa Hakko Kirin: Consultancy; Karyopharm: Consultancy; Ono Pharmaceuticals: Consultancy; Secura Bio: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; AstraZeneca: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Innate Pharmaceuticals: Research Funding; Roche/Genentech: Research Funding; Corvus Pharmaceuticals: Research Funding; Verastem: Research Funding. Oberic: Celgene: Honoraria; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; Janssen: Honoraria, Other: Support for attending meetings and/or travel; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; AbbVie: Other: Support for attending meetings and/or travel; Incyte: Membership on an entity's Board of Directors or advisory committees. Jurczak: Maria Sklodowska-Curie National Research Institute of Oncology: Current Employment; Jagiellonian University: Ended employment in the past 24 months. Greil: Sandoz: Honoraria, Research Funding; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding. Pinto: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; MSD: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau. Abrisqueta Costa: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hirata: Genentech, Inc.: Current Employment; Genentech/Roche: Current holder of stock options in a privately-held company. Jiang: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Yan: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Lee: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Flowers: AbbVie: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Epizyme: Consultancy; Roche/Genentech: Consultancy, Research Funding; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; Seattle Genetics: Consultancy; Spectrum: Consultancy; 4D: Research Funding; Acerta: Research Funding; Adaptimmune: Research Funding; Allogene: Research Funding; Amgen: Research Funding; Cellectis: Research Funding; EMD: Research Funding; Guardant: Research Funding; Iovance: Research Funding; Janssen: Research Funding; Kite: Research Funding; Morphosys: Research Funding; Nektar: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Ziopharm: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Pharmacyclics: Research Funding. Salles: Bayer: Honoraria; AbbVie: Consultancy, Honoraria; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Debiopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ipsen: Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Loxo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Consultancy; Morphosys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rapt: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Velosbio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allogene: Consultancy. OffLabel Disclosure: Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b on malignant B-cells. Polatuzumab vedotin in combination with bendamustine and rituximab (pola-BR) improved complete response rate and overall survival compared with BR alone in patients with relapsed/refractory diffuse large B-cell lymphoma. Pola-BR is approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies.

Abstract: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881–0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity. Presented to Association of Surgeons in Training (ASiT) International Conference 2018 (Edinburgh, UK), European Society of Coloproctology (ESCP) International Conference 2018 (Nice, France), SARS (Society of Academic and Research Surgery) 2020 (Virtual, UK).