ABSTRACT
Background: Severe presentation of ANCA vasculitis is a life-threatening disease despite aggressive immunodepression therapy. Complement hyperactivation is involved in pathogenesis;thus, the effect of the C5 inhibitor (eculizumab) used in severe forms of ANCA vasculitis may be a treatment option. Method(s): This is a retrospective study. Nine patients were included. Period of study: from May 2017 to May 2022. All patients received at least 3 drugs (steroids, rituximab and mycophenolate or cyclophosphamide) before eculizumab. Eculizumab was indicated as an off-label indication due to lack of improvement or clinical worsening. Result(s): Mean (SD) age: 62 (15) years. Female: 4. Three patients showed serum antiproteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) and 5 (myeloperoxidase: MPO-ANCA) and one was ANCA-negative. Six patients had an estimated glomerular filtration rate (eGFR) < 10 ml/min/1.73 m2 at presentation. Five patients had pulmonary involvement. The mean (min-max) time of follow-up after the onset of eculizumab was 27 (1-60) months. One patient ANCA-negative microscopic polyangiitis with diffuse alveolar hemorrhage needed orotracheal intubation and had a satisfactory evolution after eculizumab;however, 20 days after, the patient developed a COVID-19 infection and died. One patient who needed urgent dialysis at presentation did not recover renal function and showed a complement factor H mutation. The evolution of the other 7 patients was as follows: the median (p25-p75) eGFR increased from baseline to the end of the follow-up: 9.1(4.8-21.7)ml/min/1.73m2 to 31(13-45)ml/min/1.73m2, respectively (P=0.018) and the mild proteinuria disappeared in all patients. Alveolar hemorrhage improved in all patients within seven days after the first eculizumab administration. The median (p25-p75) doses of eculizumab administered were 1800(1800-3600) mg. One patient required eculizumab for two different periods. Conclusion(s): One patient died due to a COVID-19 infection, and one remained in chronic renal replacement therapy. Alveolar hemorrhage was well controlled in all patients. The eGFR increased significantly in 7/9 patients, and in 4/6 patients, dialysis could be withdrawn. In severe ANCA vasculitis, eculizumab should be considered for improving outcomes.
ABSTRACT
Background: Strategies for locally advanced rectal cancer LARC usually consisted of neoadjuvant concomitant chemoradiotherapy (CRT) followed by adjuvant chemotherapy, or short-course radiotherapy (SCRT). TNT is a novel approach for LARC, with several randomized clinical trials exploring its role and paving the way for implementation in clinical practice. Nevertheless, the COVID-19 pandemic represented a challenge for a timely diagnosis, implementation and follow-up of new treatment strategies in these pts. Methods: Records of all the pts diagnosed with LARC and stage IV rectal cancer evaluated in the Oncology department of Vall d’Hebron Hospital between Jan 1st, 2017 and Dec 31th 2021 were included. The period 2017-19 was considered pre-pandemic (PP) and 2020-2021 during-pandemic (DP). Patients with LARC receiving neoadjuvant and/or adjuvant treatment were analyzed, including those treated with SCRT, CRT, and TNT. Data regarding demographics, diagnosis and staging, preoperative treatment received, surgical outcomes, including treatment response, and pathological stage were collected. Results: 390 patients were included (31.28% female, 68.71% Male, median age 69). LARC pts characteristics included 123 (31.54%) either cT4 or cN2, 59 low rectal cancers, 4 with signet ring cells. Neoadjuvant treatment was done in 160 pts (CRT) and 59 pts (TNT). pCR was achieved in 20% and 22% for CRT, and TNT respectively (p0.84). 32 pts received only SCRT with 6.25% pCR. An increased ratio of stage IV pts compared to LARC was evident during the pandemic (stage IV 26.38% 2017-2019, 37.14% 2020-2021, p=0.044). The proportion of high risk LARC increased during pandemic (34.89% PP vs 39.04% DP, p=0.041). No difference was found in terms of pCR amongst the PP and DP patients (25.3% vs 27%, p=0.83) nor different strategies (TNT: 26.47% PP and 26.6% PD, p=0.98 and CRT 23.89% PP and 27.27 % PD, p=0.82). Conclusions: Efficacy of LARC neoadjuvant treatment measured by pCR was maintained in pts before and during COVID-19 pandemic despite an increasing proportion of new LARC high-risk pts. Evaluation of TNT impact in LARC outcomes was challenging because of pandemic confounding role. Real-world data in a post-pandemic setting is essential to evaluate outcome trends in LARC pts;an increase in high-risk LARC and metastatic pts should be expected. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosures: A. García Álvarez: Speaker Bureau / Expert testimony: ANGELINI PHARMA ESPAÑA;Travel / Accommodation / Expenses: Pfizer, Ipsen, Eisai Europe. All other authors have declared no conflicts of interest.
ABSTRACT
Background: SARS-CoV-2 outbreak has impacted on the management of oncological p, leading to treatment delays in a considerable number of cases. The aim of this study was to evaluate if oncological T affected negatively COVID-19 outcome. Methods: We retrospectively analyzed clinical data from p with solid tumors under active systemic T (received in the last 6 months) that were diagnosed with SARS-CoV-2 infection (defined as positive PCR) between March and 11th May 2020 in our center. Study endpoint was death due to COVID-19. We divided the patients in two groups;those who had received treatment in the last 4 weeks and those who had not. Descriptive and univariate analysis were performed to detect the effect of T type and other variables on COVID-19 related mortality. Results: A total of 70 p were included with a median follow-up of 28 days (10-47) and active oncological T had been administered in the past 4 weeks to 44 p. Median age was 66 (IQR 56-74), 23 p (52.27%) were female and 41 (93.2%) had a baseline ECOG≤1. The most frequent primary site was lung tumor (12 p [27.3%]), followed by breast (11 p [25%]) and gastrointestinal (5 p [11.4%]). Thirty-one p (70.5%) had metastatic disease and 13 (29.5%) were included in clinical trials. Twenty-four p (54.5%) received chemotherapy (CT), 14 (31.8%) targeted therapies, 9 (20.4%) immunotherapy (IT), 5 (11.4%) radiotherapy and 6 (13.6%) hormonotherapy. A total of 13 p (29.5%) received different combinations of oncological T. Death due to COVID-19 occurred in 5/22 (22.7%) p receiving CT and 6/21 (28.5%) p in the non-CT (p>0.05). Only 1/9 (11.1%) p treated with IT died compared to 11/35 (31.4%) p in the rest of the cohort (p>0.05). Age>71, comorbidities such as chronic obstructive pulmonary disease and ECOG status>2 were associated to a higher mortality. The distribution of these variables between the anticancer T groups was not different. Conclusions: Our results suggest that CT and other anticancer T might not worsen COVID-19 related mortality;nevertheless, the number of patients was small. and decision making has to be individualized. Our findings may warrant further investigation in larger studies. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie;AstraZeneca;Blueprint medicines;Boehringer Ingelheim;Bristol-Myers Squibb;Celgene;Eli Lilly;Guardant Health;Janssen;Medscape;Merck KGaA;Novartis;Pfizer;Roche;Takeda;Touchtime;Research grant/Funding (self), Research grant/Funding (institution): Fundación Merck Salud;Oncology Innovation EMD Serono. J. Carles: Advisory/Consultancy, Speaker Bureau/Expert testimony: Johnson & Johnson;Bayer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Astellas Pharma;Advisory/Consultancy: Pfizer;Sanofi;MSD Oncology;Advisory/Consultancy, Research grant/Funding (self): Roche;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZéneca;Speaker Bureau/Expert testimony: Asofarma;Research grant/Funding (self), Travel/Accommodation/Expenses: BMS;ravel/Accommodation/Expenses: Ipsen;Roche;Research grant/Funding (self): AB Science;Aragon Pharmaceuticals;Pharmaceuticals;INC;Blueprint Medicines Corporation;N Immunotherapeutics INC;Boehringer Ingelheim España, S.A.;Clovis Oncology;Cougar Biotechnology INC;Deciphera Pharmaceuticals LLC;Exelixis INC;F. Hoffmann-La Roche LTD;Genentech INC;Glaxosmithkline;Incyte Corporation;Janssen-Cilag International NV;Karyopharm Therapeutics INC;Laboratoires Leurquin Mediolanum SAS. J. Tabernero: Honoraria (self): Array Biopharma;AstraZeneca;Bayer;BeiGene;Boehringer Ingelheim;Chugai;Genentech;Genmab A/S;Halozyme;Imugene Limited;Inflection Biosciences Limited;Ipsen;Kura Oncology;Lilly;MSD;Merck Serono;Menarini;Merrimack;Merus;Molecular Partners;Novartis;Peptomyc;Pfizer;Pharmacyclics;ProteoDesign SL;Rafael Pharmaceuticals;F. Hoffmann-La Roche Ltd;): Sanofi;eaGen;Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. All other authors have declared no conflicts of interest.