Conservative management of appendicitis during COVID pandemic-our experience

Aims: Acute appendicitis is the most common surgical diagnosis with a lifetime prevalence of 7%. Appendicectomy is the gold standard treatment for acute appendicitis. Conservative management was advised and open appendicectomy recommended when surgery was unavoidable during the covid pandemic due to concerns of increased peri-operative mortality and spread of infection during aerosol generating procedures. This study describes the role of conservative management in appendicitis. Method(s): Retrospective analysis of patients who presented with right sided abdominal pain and a suspected appendicitis diagnosed clinically. Data was collected from patient notes, drug charts and operative sheet. Data was entered into an excel sheet and analysed. Result(s): 66 patients were admitted over a 6 month period from January 2020 to June 2020. There were 37 males and 29 females with a mean age of 36 years. The mean temperature was 38, mean WCC-12 and CRP-75. Antibiotics were given for 7.5 days. 48% (32 out of 66) of these patients required surgery. The total length of stay was 3.8 days. 16 patients (25%) managed conservatively were readmitted after an average of 7 days, then requiring surgery. Intra-operative findings for all patients were an inflammed or gangrenous appendix. The cost of managing patient conservatively was 1054, failed conservative followed by surgery was 3488. Conclusion(s): Appendicectomy is a procedure with a low complication rate. Nearly half the patients managed conservatively required surgery. The option of surgery versus conservative management can be discussed with patient. The cost of failed conservative management was more than three times of conservative management alone.

REAL WORLD DATA ON BORTEZOMIB-BASED THERAPY IN WALDENSTRÖM'S MACROGLOBULINAEMIA: EFFECTIVE EVEN IN MULTIPLY TREATED PATIENTS INCLUDING PRIOR BTKINHIBITORS

Background: Waldenström macroglobulinemia (WM) is an indolent lymphoma with a prolonged disease course which typically follows a remitting and relapsing trajectory, eventually leading to treatment resistance. Several treatment options exist including Bruton tyrosine kinase inhibitors (BTKi), rituximab-containing regimens, and bortezomibcontaining regimens. Treatment selection is based on patient performance status, disease characteristics, drug tolerability and availability. Aims: To assess the effectiveness and tolerability of bortezomib-based regimens in WM. Methods: Data for patients who had Bortezomib-containing regimens between 2010 and 2021 from 6 centres in the United Kingdom were retrospectively reviewed. Data was acquired from the WMUK Rory Morrison Registry. Research ethics approval was obtained. Results: Thirty-four patients were identified: 32/34 had Bortezomib-containing regimens once and 2/34 had >1 Bortezomib-containing regimens on separate occasions, giving a total of 38 subcutaneous Bortezomib-containing regimens administered at bi-weekly and weekly schedules. Median age was 62 years (37-87), with a median of 2 prior lines of therapy (0-7), at a median duration of 49.6 months from date of WM diagnosis (0.7-422). 5 patients received a prior BTKi, with the Bortezomib regimen prescribed following a median of 3 prior lines of therapy (2-5) in this group. Patients who were treated at first line had elected for non-chemotherapy regimens. Median performance status was 1 (0-2) in 23 evaluable patients. The median M-protein at initiation was 34.5g/l (8-60) with bone marrow infiltration 70%, and haemoglobin 94g/l (88-107). A median of 5 cycles (1-8) were delivered and 65% (13/20) received a dose of 1.6mg/m2 and 35% (7/20) received 1.3mg/m2. Grade (G) 1 to 2 neuropathy occurred in 19% (5/26) of evaluable patients but did not result in treatment cessation in any case. Six of 25 (24%) needed a dose reduction, the majority due to G1-2 neuropathy (67%;4/6). Gastrointestinal disturbance occurred in 12% (3/26) patients, 1 required admission with G4 diarrhoea and remaining cases were G1. Of 34 evaluable cases, major response rate (≥ PR) was 74% (5 CR, 6 VGPR, 14 PR). 62% (8/13) of patients receiving 1.6mg/m2 achieved a major response and 86% (6/7) of those who received 1.3mg/m2. Three of 5 patients who had prior BTKi achieved PR, 1 MR, 1 SD. Two patients had treatment discontinued due refractory disease. The overall median time to best response was 81 days from end of treatment. Six of 19 (26%) evaluable patients achieved best response during therapy. Two patients died during treatment due to infection (COVID;respiratory sepsis), not attributable to disease relapse. Eighteen patients (60%;18/30) had treatment after bortezomib regimens at a median of 5.3 months (0-75) and are alive. Median follow up was 30 months (1-111). Twenty-one evaluable patients (72%;21/29) were alive at the end of follow up. Image: Summary/Conclusion: This retrospective real-world analysis shows that bortezomib-containing regimens have utility in WM with effective major response rates even in those with multiple prior lines of therapy and heavy marrow infiltration including BTKi failures. Lower bortezomib doses are effective, and GI and neurotoxicity are manageable with dose reductions but no treatment discontinuations in this real-world cohort indicating an acceptable safety profile.

TREATING BING-NEEL SYNDROME USING A TAILORED APPROACH: EXPERIENCE OF A SPECIALIST NEUROHAEMATOLOGY CLINIC

Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Global Waldenström's Macroglobulinemia Patient-Derived Data Registry, Whimsical, Highlights Real-World Treatment Outcomes and COVID-19 Data

Introduction: WhiMSICAL (Waldenström's Macroglobulinemia Study Involving CArt-wheeL) is the first global Waldenström's Macroglobulinemia (WM) registry capturing patient-derived data to complement scarce clinical trials data in this rare cancer (Tohidi-Esfahani et al, Am J Hematol 2021). The registry was interrogated to identify real-world first line treatment outcomes, quality of life (QoL) and coronavirus disease 2019 (COVID-19) data. Methods: The registry captures data through www.cart-wheel.org, an online rare cancer database, utilizing a tailored questionnaire developed by clinician and patient investigators. WM patients complete consent online, then enter symptom, pathology, treatment, QoL (EORTC QLQ-C30) and COVID-19 data, and can return to update their data on an ongoing basis. Recruitment is driven by social media messaging by the International Waldenström's Macroglobulinemia Foundation investigators. Time to next treatment (TTNT) was assessed from start of first therapy to start of second therapy. Patients without a documented second therapy were censored at the time of last edit to their account. COVID-19 questions included testing, disease severity, vaccination and impact on WM management. Results: As of July 2021, 558 patients from 20 countries have participated in the registry, predominantly from USA (50%), Australia (22%) and the UK (9%). Median age at diagnosis was 61 years (range 24-83) with male predominance (61%). 371 patients documented first-line therapies, with a total of 54 unique therapeutic combinations listed. The seven most common therapies were: bendamustine rituximab (BR, n=94), rituximab monotherapy (Rit., n=52), dexamethasone rituximab cyclophosphamide (DRC, n=33), ibrutinib (n=25), bortezomib dexamethasone rituximab (n=15), rituximab cyclophosphamide vincristine prednisolone (n=14) and chlorambucil (n=10). Comparison of TTNT was limited to the four most common first-line therapies: BR, Rit., DRC, with zanubrutinib (n=5) and ibrutinib plus rituximab (n=2) adding to the first line Bruton tyrosine Kinase inhibitor (BTKi) cohort (n=32). Median ages for the BR, BTKi, DRC and Rit. cohorts were 65, 66, 61 & 65 years, respectively. More patients in the BR cohort listed comorbidities (37%), with BTKi-treated patients reporting the least (19%). Pre-treatment disease burden (median IgM and hemoglobin) trended to being higher in the BR and DRC cohorts (figure 1B-D, IgM p=0.24, Hb p=0.27). At median follow up ranging from 31 to 39 months, BR had superior TTNT to DRC (median: not reached and 104 months, p=0.007, figure 1C) and Rit. (median 26 months, p < 0.0001, figure 1D), and trended to superiority compared to BTKi (median not reached, p=0.08, figure 1B). Median TTNT for the entire cohort (n=371) was 108 months (median follow up 55 months, figure 1A). Assessment of QoL was conducted in all patients (any line of treatment) and compared between patients currently on BTKi therapy (n=64) and patients not exposed to BTKi and treated within the last 12 months (n=84). The expanded BTKi cohort reported better QoL, with mean EORTC QLQ-C30 global scale of 82 ± 14.4 compared to the BTKi-naïve cohort mean 73.4 ± 20.9, p=0.005. This was despite more prior lines of treatment (median 2 [IQR 1-4] compared to 1 [IQR 1-1];p<0.0001). 324 (58%) patients responded to the COVID-19 questions. 144/324 (44%) had undergone testing for COVID-19, with 11 (8%) returning a positive result;none after vaccination. Median length of symptoms was seven days (range 2-30), with two hospitalized, one requiring intensive care. Both hospitalized patients were on second line ibrutinib. Of 211 responses regarding vaccination status, 15 (7%) were not vaccinated, eight due to availability, five due to personal choice and two due to clinician advice. Regarding impact of the pandemic on their WM management, 5% had treatment schedule disruption and 53% reported reduced face-to-face consultations. Conclusion: The WhiMSICAL registry provides a scientifically robust and ethically approved portal for the patients' voice. The data highligh the real-world efficacy of combination chemoimmunotherapy, particularly first-line BR, and suggest a better QoL with BTKi than other therapies. As this global data platform grows, the breadth of data allows for new insights into WM with patient reported outcomes advancing knowledge and facilitating treatment decisions for clinicians and patients. [Formula presented] Disclosures: D'Sa: Sanofi: Honoraria;BeiGene: Honoraria, Research Funding;Janssen Cilag: Honoraria, Research Funding. Kersten: Roche: Consultancy, Honoraria, Other: Travel support, Research Funding;Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support;Novartis: Consultancy, Honoraria, Other: Travel support;BMS/Celgene: Consultancy, Honoraria;Takeda: Research Funding;Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding;Celgene: Research Funding. Thomas: Acerta Pharma: Research Funding;Ascentage Pharma: Research Funding;BeiGene: Membership on an entity's Board of Directors or advisory committees;BMS: Research Funding;Pharmacyclics: Membership on an entity's Board of Directors or advisory committees;X4 Pharma: Research Funding;Genentech: Research Funding. Palomba: Ceramedix: Honoraria;Rheos: Honoraria;Nektar: Honoraria;Priothera: Honoraria;Lygenesis: Honoraria;WindMIL: Honoraria;Wolters Kluwer: Patents & Royalties;Juno: Patents & Royalties;BeiGene: Consultancy;Kite: Consultancy;Magenta: Honoraria;Seres: Honoraria, Other: Stock, Patents & Royalties, Research Funding;PCYC: Consultancy;Notch: Honoraria, Other: Stock;Novartis: Consultancy;Pluto: Honoraria. Olszewski: Acrotech Pharma: Research Funding;Celldex Therapeutics: Research Funding;TG Therapeutics: Research Funding;PrecisionBio: Research Funding;Genentech, Inc.: Research Funding;Genmab: Research Funding. Trotman: PCYC: Research Funding;roche: Research Funding;BMS: Research Funding;TAKEDA: Research Funding;JANSSEN: Research Funding;beigene: Research Funding.