ABSTRACT
Background: Previous studies had demonstrated that patients with hematologic malignancies had suboptimal antibody response after receiving COVID-19 vaccines, especially among those having previously treated with anti- CD20 monoclonal antibodies. Method(s): Adult patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL) were enrolled before receiving the second dose of SARS-CoV-2 vaccine. Determinations of anti-SARS-CoV-2 spike and nucleocapsid IgG titers were performed every 1-3 months, after they received the second and the third dose of SARS-CoV-2 vaccine, respectively. Patients were excluded from analysis if they were diagnosed with COVID-19. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from subsequent analyses. Result(s): A total of 85 participants were enrolled, including 42 (49.4%) with diffused large B-cell lymphoma, and 13 (15.3) with follicular lymphoma and 9 with CLL. 72 (84.7%) participants had received anti-CD20 monoclonal antibodies, with a median interval of 24 months between last anti-CD20 treatment and the second dose of vaccine, and 21 (24.7%) had HIV infection. Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/ mL within 12 weeks after the second dose of vaccine included HIV infection (adjusted odds ratio [aOR], 0.14;95% CI, 0.04-0.51), active hematologic disease (aOR, 5.50;95% CI 1.42-21.32), receipt of anti-CD20 monoclonal antibodies (aOR, 6.65;95% CI 1.52-29.07), and receipt of two doses of homologous mRNA vaccination (aOR, 0.17;95% CI 0.05-0.56). In the participants having previously treated with anti-CD20 regimen, only 8.6% achieved an antibody response ( >141 BAU/mL) in the first year, while 78.3% achieved anti-spike IgG titer > 141 BAU/mL after two years post B-cell depleting treatment. After the third dose of SARS-CoV-2 vaccine, 53.6% achieved an antispike IgG titer > 141 BAU/mL in the first year post anti-CD20 treatment. Conclusion(s): Our study demonstrated that previous treatment with anti-CD20 monoclonal antibodies was associated a lower antibody response among patients with lymphoproliferative disorders receiving two doses of SARS-CoV-2 vaccine. While two doses of SARS-CoV-2 vaccines might not be sufficient even one year apart from the last dose of rituximab, a third dose of vaccine may boost anti-spike IgG particularly in the subset of recent exposure to rituximab. Anti-spike IgG determined 1-3 months after the second (A) / third (B) dose of COVID-19 vaccine, stratified by the interval between last anti-CD20 regimen and the second / third dose of COVID-19 vaccine. (Figure Presented).
ABSTRACT
Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.
ABSTRACT
[Formula presented] [Formula presented] Fig. 1. Impact des anti-CD20 sur le risque de COVID-19 severeCopyright © 2023
ABSTRACT
Background. Rituximab (RTX) is a chimeric monoclonal antibody that binds the CD20 molecule on the surface of B cells and leads to B cell depletion. RTX is recommended by the European League Against Rheumatism (EULAR) as off-label in patients affected by idiopathic inflammatory myopathies (IIM). The real-world experience has shown that hypogammaglobulinemia occurring early after anti-CD20 treatment can be multifactorial (active disease, effect of other drugs) and usually transient, with a minimal increase in the risk of infections. The present study aimed to analyse the differences in the rate of RTX-associated hypogammaglobulinemia in a cohort of IIM patients in clinical practice, as well as the onset of major infections and its correlation with hypogammaglobulinemia. Methods. Patients followed at Rheumatology Unit of Siena University Hospital from January 2020 to September 2021 were retrospectively enrolled. Inclusion criteria were as follows: fulfilment of disease-specific classification criteria 2017 EULAR criteria and /or Peter and Bohan criteria for dermatomyositis (DM) and polymyositis (PM), positivity of anti-synthetase antibody and typical clinical features for anti-synthetase syndrome (ASS) and the measurement of serum Ig levels at the time of RTX administration (maximum 2 weeks before) (T0) and 6 (T1) to 12 (T2) months later, consistently with previous studies. Ig serum levels, measured by standard nephelometry (normal ranges: IgG 700-1600 mg/dL, IgM 40-240 mg/dL, IgA 70-400 mg/dL) were assessed as part of routine clinical care. Hypogammaglobulinemia was defined as moderate (serum IgG <600 mg/dL) and severe (IgG <400 mg/dL), as previously reported. Results. Seven patients (mean+/-SD, 57.3+/-19.7 years;7 female) were enrolled. Three of them had diagnosis of DM, three ASS and one PM. Two patients showed MDA5-positivity, two JO1-positivity, one TIF1-gamma-positivity, one PL7-positivity and the other one PM/Scl-positivity. All patients had at least two organs involved, and 4 out of 7 (57%) suffered from interstitial lung disease. Before starting RTX treatment, three and four patients underwent at least one and two synthetic immunosuppressants. All patients underwent low dosage of corticosteroids, and four patients underwent concomitant synthetic immunosuppressants (2 hydroxychloroquine and 2 MTX). IgG concentrations were statically lower at T2 compared to those at baseline (p=0.0391). None of them showed severe hypogammaglobulinemia. Similarly, IgM concentration significantly decreased at T2 compared to those at baseline (p=0.0078). Two patients showed major infections and two patients had paucisymptomatic COVID-19 (one of them had twice). Corticosteroids dosages were inversely correlated with IgG T2 concentrations (p=0.040, r=-0.919). Conclusion. Hypogammaglobulinemia following RTX is uncommon in IIM and is more likely in patients with high glucocorticoids, immunosuppressants and CYC exposure. IgG monitoring at least 6 months after RTX treatment may be useful in stratifying patients to identify those who require closer monitoring. These results shine a spotlight for increased awareness of the role of immunoglobulin measurement before maintenance doses of RTX.
ABSTRACT
Background and Importance On March 28th 2022, nirmatrelvir/ ritonavir was marketed in Spain. The Spanish Agency for Medicines and Medical Devices (AEMPS) established criteria to prioritise its administration in patients at high risk of progression to severe COVID. Data regarding the effectiveness and safety of nirmatrelvir in preventing severe coronavirus disease outcomes are limited. Aim and Objectives To assess the effectiveness and safety of nirmatrelvir/ritonavir in patients at high risk for severe COVID-19. Material and Methods Prospective descriptive study from April to August 2022 of patients treated with nirmatrelvir/ritonavir. Sociodemographic variables, vaccination status, hospital admission, high risk factors for progression and concomitant treatment were recorded. Readmissions were recorded within 30 days of the end of antiviral treatment. Results 53 patients were included with a mean age of 64 years, 51% women and 49% men. 57% were vaccinated with 3 doses, 17% with 2 doses, 9% with 4 doses, 6% with 1 dose and 11% were not vaccinated. 34% (18/53) were hospitalised at the time of initiation of treatment. The most prevalent high-risk criteria were: 24% active treatment with myelotoxic chemotherapy, 21% treatment in the previous 6 months with anti-CD20 drugs, 14% over 80 years vaccinated with some risk factor for progression, 7% patients with onco-haematological treatment and 7% in treatment in the previous 3 months with inhibitors of the proteinkinase. 3 treatments were performed off-label for persistent covid. The mean number of days from the onset of symptoms to the start of treatment was 1.6 days. 23% of patients required dose adjustment due to renal impairment. 53% required adjustment of chronic treatment for interactions, mainly with metamizole, statins, fentanyl and diazepam. 2 patients received remdesivir and sotrovimab, 2 remdesivir and another two sotrovimab. 4 (7%) patients were readmitted within 30 days after the end of treatment with nirmatrelvir ritonavir, 1 of them with persistent covid. One patient stopped treatment for hives. Conclusion and Relevance Nirmatrelvir ritonavir has been shown to be a safe and effective drug in high-risk patients of progression to severe covid.
ABSTRACT
Background: Multiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use;however, there is little data in our Middle East and North Africa region (MENA) identifying clinical characteristics of MS associated with worse COVID-19 outcomes. Material(s) and Method(s): This a nationwide, multicenter, retrospective cohort study conducted between March 2020 and February 2021 and included MS patients with a suspected or confirmed COVID-19. Using data collected from the MENACTRIMS registry and local COVID-19 registries, the association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes and severity of COVID-19 illness were evaluated by multivariate logistic models. Result(s): A total of 600 MS patients with suspected (n=58) or confirmed (n=542) COVID-19 (mean age: 36.4 +/- 10.16 years;414 (69%) females;mean disease duration: 8.3+/- 6.6 years) were analyzed. Seventy-three patients (12.2%) had a COVID-19 severity score of 3 or more, and 15 patients (2.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 559 patients (93.2%) were receiving disease-modifying therapy (DMT). There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients treated with DMTs relative to untreated patients (82.9% vs 17.1%;P < .001), from whom the majority (n=117;19.7%) were maintained on anti-CD20 therapies such as ocrelizumab and rituximab. Comorbidities mainly hypertension and cardiovascular diseases, progressive MS, disease duration, and EDSS were associated with severe or worse COVID-19 disease outcome. Multivariate logistic regression analysis showed that older age (odds ratio per 10 years, 1.5 [95%CI, 1.1-2.0]), male gender (OR, 2.1 [95%CI. 1.2-3.8]), obesity (OR, 2.8 [95%CI, 1.3-5.8]), and treatment ocrelizumab/rituximab (OR for ocrelizumab, 4.6 [95%CI. 1.2-17.7], OR for rituximab, 14.1 [95%CI, 4.8-41.3]) or off-label immunosuppressive medications such as azathioprine or mycophenolate mofetil (OR, 8.8 [95%CI. 1.7-44.0]) were risk factors for moderate to severe COVID-19 requiring hospitalization. Surprisingly, smoking and diabetes were not identified as risk factors for severe COVID-19 disease in our cohort. Conclusion(s): In this registry-based cohort study of patients with MS, age, sex, EDSS, obesity, progressive MS were independent risk factors for severe COVID-19. Moreover, there was an association found between exposure to anti-CD20 DMTs and COVID-19 severity. Knowledge of these risk factors may help improve the clinical management of MS patients with COVID-19 infection.Copyright © 2022
ABSTRACT
Background: By depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines' humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear. Objective: To estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients. Methods: This retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were <25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2. Findings: Forty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients. Conclusions: Nine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Immunoglobulin G , Retrospective Studies , Rituximab/adverse effects , SARS-CoV-2ABSTRACT
The review presents the results of a combined analysis of literature data and own clinical observations regarding the safety and feasibility of using monoclonal anti-CD20 antibodies in the treatment of B-cell lymphoproliferative diseases during the COVID-19 pandemic. The main points of the pathogenesis of the influence of monoclonal anti-CD20 antibodies on the course of COVID-19 are described. The current trends in the modification of the accepted algorithms of lymphoproliferative diseases therapy with the inclusion of monoclonal anti-CD20 antibodies are summarized, and the possibilities of specific prevention by vaccination against COVID-19 are also considered. Copyright © 2022 ABV-Press Publishing House. All rights reserved.
ABSTRACT
Purpose: We examined a positivity of corona virus antibody in kidney transplant recipients who received two-doses BNT162B2 (mRNA) vaccination during the beginning 6 months in 2021. Method(s): The subjects include 111 kidney transplant recipients who received two-doses BNT162B2 (mRNA) vaccination, consisting of 61 male and 50 females, 53.7+/-14.7 years old on average. Healthy 10 volunteers were also enrolled in this study as a control group. We adopted LABScreen COVID plus beads (One Lambda) as an antibody reagent to detect antibodies against corona viruses including 5 types structural proteins such as extracellular domain (ECD), Spike 1, Spike 2, receptorbinding domain (RBD) and nucleoside. Result(s): Among 111 recipients, 46 recipients showed positivity (41%), whilst all control showed positivity (100%). Among 100 recipients taking tacrolimus, 37 recipients showed positivity, although 9 recipients out of 10 taking cyclosporine showed positivity (90%). It is noteworthy that recipients receiving rituximab (CD20 antibody) significantly shows lower rate of antibody positivity. The period between vaccination and rituximab administration is closely related to the positivity of antibody positivity. In recipients without rituximab administration, lower trough level for tacrolimus and MMF is related to higher positivity of antibody production. Positivity pattern in 5 protein fragments shows individually various different in transplant recipients, while it shows stable pattern in healthy volunteers. Conclusion(s): Kidney transplant recipients showed lower positivity of corona virus antibody compared to healthy volunteers, which is deeply related to immunosuppression in the past. This assay in this study yields reproductive excellent results for corona virus antibody. The assay helps us to find the appropriate booster vaccination time and doses on the basis of these past results. (Figure Presented).
ABSTRACT
SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after transplantation. While there is evidence that hematologic malignancy is associated with increased severity in COVID-19 infection, there is little description of PTLD and COVID-19. CASE PRESENTATION: A 68-year-old man and a 68-year-old female, both of whom had prior renal transplantation, were admitted to the hospital with COVID-19 pneumonia. Both patients were vaccinated against COVID-19, though were negative for spike protein antibodies. The man was treated with remdesivir and the woman was treated with remdesivir and dexamethasone. Both patients improved and were discharged. Within a month, both had recurrent symptoms of dyspnea and fever requiring re-admission. They were hypoxic, the man requiring high flow nasal cannula and the woman requiring nasal cannula to maintain SpO2>90%. They had positive COVID-19 PCR tests, with cycle threshold lower than in their initial admissions, as well as chest imaging with bilateral infiltrates. The man had a pleural effusion with cytology consistent with PTLD and perinephric mass and retroperitoneal lymphadenopathy with biopsy confirming PTLD. The woman had a renal sinus mass with biopsy confirming PTLD. Both patients were treated with another 5 days of remdesivir and started on dexamethasone. The medical team discussed monoclonal antibody treatment, but the patients did not meet EUA criteria and compassionate use request was denied. To treat PTLD, both were initiated on Rituximab, Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP). Since then, both patients have had complicated and prolonged hospital courses. The woman developed renal failure and severe C.diff colitis complicated by toxic megacolon requiring total colectomy. The man developed renal failure, CMV viremia, and pseudomonas UTI. The patients were able to be weaned to room air, though ultimately the woman had to be intubated due to poor mental status and remains on low oxygen settings. Both patients continue to be persistently positive for COVID-19 by PCR. DISCUSSION: This case illustrates diagnosis and treatment of PTLD in two patients with COVID-19 infection. Of particular interest was the use of Rituximab, an anti-CD-20 antibody which impairs humoral immunity, in the treatment of PTLD, as the drug has been associated with increased risk of severe COVID-19 infection. Rituximab was particularly concerning as both patients had persistent COVID-19 without development of immunity despite prior vaccination, and both continue to be positive despite two months of active infection. The patients had improvement of their respiratory status, though have had poor and complicated clinical courses with renal and infectious complications. CONCLUSIONS: Treatment of PTLD in patient's with active COVID-19 may impair ability to clear virus, though impact on outcomes is unclear. Reference #1: Simpson-Yap, S., de Brouwer, E., Kalincik, T., Rijke, N., Hillert, J. A., Walton, C., Edan, G., Moreau, Y., Spelman, T., Geys, L., Parciak, T., Gautrais, C., Lazovski, N., Pirmani, A., Ardeshirdavanai, A., Forsberg, L., Glaser, A., McBurney, R., Schmidt, H., … Peeters, L. (2021). Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis. Neurology, 97(19). https://doi.org/10.1212/WNL.0000000000012753 Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A… Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1). https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Passamonti, F., Cattaneo, C., Arcaini, L. Bruna, R., Cavo, M., Merli, F., Angelucci, E., Krampera, M., Cairoli, R., della Porta, M. G., Fracchiolla, N., Ladetto, M., Gambacorti Passerini, C., Salvini, M., Marchetti, M., Lemoli, R., Molteni, A., Busca, A., Cuneo, A., … Corradini, P. (2020). Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. The Lancet Haematology, 7(10). https://doi.org/10.1016/S2352-3026(20)30251-9 DISCLOSURES: No relevant relationships by Ian Mahoney No relevant relationships by Caroline Motschwiller
ABSTRACT
SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The SARS-CoV-2 pandemic quickly spread throughout the world after it was first identified in Wuhan, China in 2019. Severe cases of hypoxic respiratory failure have since filled hospitals over the past few years. We present a case of an immunosuppressed patient with persistent respiratory failure from SARS-CoV-2, with a failure to mount antibody response, treated with convalescent plasma. CASE PRESENTATION: We present a 54-year-old female with a past medical history significant for rheumatoid arthritis on immunosuppression with methotrexate, prednisone, sulfasalazine, and rituximab who presented with diarrhea, cough, and shortness of breath. She was unvaccinated and tested positive for COVID-19 pneumonia, which was treated with corticosteroids and Remdesevir. CT thorax revealed diffuse infiltrates (Figure-1). She had progressive hypoxia requiring ICU stay and her course was complicated by inferior wall STEMI, requiring Intra-aortic balloon pump and intubation given worsening hypoxia. She had progressive improvement and was discharged from the hospital on 4 L of supplemental oxygen after a 30-day hospital stay. She presented two days after discharge with cough, fevers and increasing oxygen requirements up to 100% high flow nasal cannula. She was septic and was treated with steroids and antibiotics. She was febrile despite broad spectrum antibiotics. CT thorax demonstrated diffuse infiltrates worsened from the previous and steroid dosing was increased (Figure-2). No obvious source of infection was found, and further evaluation revealed positive Covid-19 RT-PCR. Despite her initial infection occurring two months prior, COVID-19 anti-spike and anti-nucleocapsid antibodies were negative. She was treated with two doses of convalescent plasma and had improvement in her oxygenation, going from 80% high-flow nasal cannula to 6L of supplemental oxygen within two days of administration. DISCUSSION: It's unclear whether immunosuppressed patients with rheumatologic disease are at an increased risk of severe SARS-CoV-2 infection. However, the use of immunosuppressants places patients at risk of an improper immune response to infection. In immunocompetent patients, the typical time to negative SARS-CoV-2 RT-PCR is 3 weeks after positivity (1), and most patients develop antibodies within 2-3 weeks after viral exposure (2). Anti-CD20 monoclonal antibodies like rituximab, commonly used for rheumatologic diseases, can hinder humoral immunity, and impair vaccine response (3). Given our patient's immunosuppressive regimen, we suspect she failed to mount an immune response to COVID-19, resulting in 56 days of infection without an adequate antibody response, successfully treated with convalescent plasma. CONCLUSIONS: Patients with significant immunosuppression regimens may fail to produce antibody responses to SARS-CoV-2, resulting in prolonged infection. Reference #1: Rodríguez-Grande, C., Adán-Jiménez, J., Catalán, P., Alcalá, L., Estévez, A., Muñoz, P., Pérez-Lago, L., de Viedma, D. G., Adán-Jiménez, J., Alcalá, L., Aldámiz, T., Alonso, R., Álvarez, B., Álvarez-Uría, A., Arias, A., Arroyo, L. A., Berenguer, J., Bermúdez, E., Bouza, E., … de la Villa, S. (2021). Inference of active viral replication in cases with sustained positive reverse transcription-PCR results for SARS-CoV-2. Journal of Clinical Microbiology, 59(2). https://doi.org/10.1128/JCM.02277-20 Reference #2: Boechat, J. L., Chora, I., Morais, A., & Delgado, L. (2021). The immune response to SARS-CoV-2 and COVID-19 immunopathology – Current perspectives. In Pulmonology (Vol. 27, Issue 5). https://doi.org/10.1016/j.pulmoe.2021.03.008 Reference #3: Eisenberg, R. A., Jawad, A. F., Boyer, J., Maurer, K., McDonald, K., Prak, E. T. L., & Sullivan, K. E. (2013). Rituximab-treated patients have a poor response to influenza vaccination. Journal of Clinical Immunology, 33(2). https://doi.org/10.1007/s10875-012-9813-x DISCLOSURES No relevant relationships by Issa Makki No relevant relationships by John Parent No relevant relationships by Jay Patel No relevant relationships by Ruchira Sengupta
ABSTRACT
SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Exposure to anti-CD20 treatment affects B cell functions involved in anti-COVID immunity and impacts the clinical course of infection. We present two patients with persistent respiratory symptoms and persistent SARS-COv-2 PCR positivity months after initial infection. The aim of presenting these cases is to highlight how exposure to Rituximab can result in patients having significantly prolonged SARS-CoV-2 infections that may require special treatment compared to immunocompetent patients. CASE PRESENTATION: Patient A is a 46-year-old man with a history of marginal zone lymphoma, who was treated with six cycles of bendamustine with rituximab and monthly maintenance rituximab. He has been hypoxic for 7 months after COVID infection with ground glass opacities on imaging, elevated CRP of 58.4, positive PCR, undetectable CD3/CD4 and low cycle threshold of 28, suggesting rapid active viral replication. COVID IGG was negative. T cell subsets counts were undetectable. IgG 351, IgA 59, IgM less than 10. He was treated with a 10-day course of Remdesevir and steroids. Given lack of humoral immunity, he was given convalescent plasma. At discharge he developed positive COVID IgG and remained COVID positive by PCR. He had complete resolution of hypoxia. Patient B is a 68-year-old man with a history of chronic lymphocytic leukemia, who was treated with six years of rituximab maintenance therapy, last rituximab was three years ago. He was diagnosed with SARS-CoV-2 three months prior to admission with worsening hypoxia. He remained PCR positive with persistent respiratory symptoms. At readmission his imaging showed ground glass opacities, CRP 6.6 and cycle threshold was 27.8. The follow studies were abnormally low:IgG 541, IgA 25, IgM 14, absolute CD3 171, absolute CD4 68. He was treated with remdesivir, steroids, granulocyte colony stimulating factor and sotrovimab. Despite these therapies, his hypoxia worsened, and he pursued comfort care. DISCUSSION: There are reports of patients receiving B cell depleting therapy who have persistent shedding of viable SARS-CoV. Persistent viral infection may be suspected in patients with relapsing symptoms, elevated CRP, D-dimer and active ground glass changes imaging. Low T cell subsets and low immunoglobulin levels indicate a CD20 related impairment of adaptive immunity. Time to viral clearance appears to be prolonged compared to general population in immunocompromised patients. There is some published experience using convalescent plasma in this setting. SARS-CoV-2 viremia has been demonstrated to predict adverse outcomes. Median cycle threshold has been shown to be lower, reflecting a high viral load comparable with acute infectious phase of COVID. CONCLUSIONS: To achieve stable clinical responses this subset of patients may benefit from early administration of combination regimens, including both passive immunotherapy and prolonged antiviral treatment. Reference #1: Furlan A, Forner G, Cipriani L, Vian E, Rigoli R, Gherlinzoni F, Scotton P. COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge. Front Immunol. 2021 Nov 3;12:763412. doi: 10.3389/fimmu.2021.763412. PMID: 34804051;PMCID: PMC8595333. DISCLOSURES: No relevant relationships by Cheryl Augenstein Primary Investigator relationship with Boehringer Ingelheim Please note: 2/2022-2/2024 Added 04/01/2022 by A. Thanushi Wynn, value=Grant/Research Support
ABSTRACT
Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders (IMIDs) treated with specific immunosuppressants and immunomodulating agents. The objective of this study is to investigate the humoral immune response after SARS-CoV-2 vaccination in patients using immunosuppressive and immunomodulating mono- and combination therapies, focussing on frequently prescribed therapies for inflammatory neuromuscular diseases. Methods: National prospective observational cohort study in selected patients with prevalent IMIDs including neuromuscular disease, and immunosuppressive or immunomodulating monotherapy (n=1273), combination therapies (n=419), patients without immunosuppressants (n=473), and healthy controls (n=174). Anti-RBD IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses, i.e. vaccination after previous SARS-CoV-2 infection, were studied as a proxy for recall responses. Findings: Sera from 1869 participants without and 470 participants with previous SARS-CoV-2 infection were analysed. We included 168 (7 2%) patients with inflammatory neuropathies and myopathies, and 127 (5 4%) patients with myasthenia gravis. Humoral responses did not differ between disorders. Anti-CD20 therapy and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks (RR) for reaching seroconversion following standard vaccination (RR: 0 32 and 0 61 respectively). The monotherapies corticosteroids, purine antagonists, methotrexate, mycophenolate mofetil and IVIg were not associated with a lower RR for reaching seroconversion (RR: 0 97, 0 98, 1 01, 0 86, and 0 99, respectively). Similarly, corticosteroids combined with either methotrexate or purine antagonists was not associated with a lower RR for reaching seroconversion (RR 0 89). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments but not for anti-CD20 therapies. Most immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that, in subgroups, did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment. Interpretation: Humoral responses following vaccination are impaired by specific immunosuppressants, most relevant for neuromuscular diseases being anti-CD20 and mycophenolate mofetil combination treatments. After standard vaccination regimens most immunosuppressants show equal seroconversion to controls although antibody titres may be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate in loss of (short term) protection. Alternatively, in immunosuppressants showing poor humoral responses after standard vaccination regimens such as, a third vaccination resulted in additional seroconversion in mycophenolate mofetil combination treatments whereas the effect for anti-CD20 therapy was limited.
ABSTRACT
Background: Hematological malignancies (HM) patients treated with anti-CD20s are at a higher risk for COVID-19 complications, however, little is known about the difference between these agents. Aim: To investigate the prognosis of HM COVID-19 pateints treated with obinutuzumab in comparison to rituximab. Methods: Single-center population-based cohort study including all HM patients treated with anti-CD20s from June 2021 to April 2022. Diagnosis of COVID-19 was based on positive SARS-CoV-2 PCR omicron variant. The Median follow-up was four months. Results: Among 143 HM patients, 47 were diagnosed with COVID- 19, 27 in the rituximab group and 20 in the obinutuzumab group. All obinutuzumab-treated patients had indolent HM, versus only 40.7% among the rituximab group (p <0.001). 13/20 of the obinutuzumab group (65.0%) received anti-CD20s as maintenance therapy, while most of the rituximab patients, 21/27 (77.8%) were on induction phase therapy (p = 0.003). COVID-19 prognosis was worse among obinutuzumab patients with higher admission rates (60.0% vs. 25.9%, p = 0.019), more patients with severe-critical disease (35.0% vs.7.4%, p = 0.017), and accounts for all mortality cases (3/20 vs. 0/27, p = 0.038). Conclusions: Omicron-variant COVID-19 disease outcome was worse among HM patients treated with obinutuzumab comparing to rituximab. As this treatment has not been shown to increase overall survival when given as maintenance, In our opinion, it may be prudent to delay treatment with obinutuzumab or replace it with a less potent anti-CD20 as long as the COVID-19 epidemic continues.
ABSTRACT
Background: Immunodeficient (ID) patients are among risk groups for severe disease after SARS-CoV2 (CoV2) infection. Despite high population immunity, ID patients remain difficult to medically advice due to their impaired immunity during an evolving CoV2 strains pandemic. Aim: We examined if durable immunisation to CoV2 infection or vaccination is developed. Serology cannot answer this since IgG replacement therapy now contains CoV2 antibodies. Instead, a cellular diagnostic test for patients' CoV2 memory T cells was used Methods: We included 13 ID patients (aged 34-78;7 female) who were vaccinated against CoV2 or previously infected: 5 with common variable immunodeficiency (CVID) and 8 with B cell deficiency (BCD) due to anti-CD20 or BTK inhibition therapy. Peripheral blood mononuclear cells isolated from whole blood were cultured with CoV2 spike protein or peptides for 7 days, then measured for T cell activation markers by flow cytometry. Results: CoV2 spike specific CD4 or CD8 T cells were detectable in 7/8 BCD and all CVID patients. However, only 3/5 CVID and 6/8 BCD patients had both CD4 and CD8 T cell responses. Conclusion: Genuine CoV2 T cell responses are detectable with a cellular diagnostic test in CVID and BCD patients after immunisation. As ID patients are heterogenous, a diagnostic test for memory T cells against CoV2 gives clinicians evidence of a patient's own immune response beyond passive IgG replacement therapy. This aids in consulting advice for infection avoidance strategies and indication for urgent treatment with monoclonal antibodies against CoV2.
ABSTRACT
Background: Patients with hematological malignancies are at a higher risk of developing severe form and protracted course of COVID-19. Remdesivir, an inhibitor of RNA polymerase was identified early as a promising therapeutic regimen for COVID-19, while convalescent plasma (CP) therapy with anti-SARS-CoV-2 antibodies can aid the treatment of COVID-19 in B-cell depleted patients. Aims: Here we investigated whether the combination of externally administered immunoglobulins (Ig) via CP therapy and specific inhibition of viral replication might be sufficient to effectively treat B-cell depleted patients with COVID-19. Methods: We enrolled a series of 20 consecutive patients who suffered from various hematological malignancies with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. These patients demonstrated a profound B-cell lymphopenia based on flow cytometry analysis of peripheral blood lymphocyte subpopulations. Consequently, they showed undetectable baseline anti-SARS-CoV-2 Ig levels before CP therapy according to anti-SARS-CoV-2 nucleocapsid-and S1-RBD-specific total Ig tests. Each patient received a complete course of remdesivir and at least one unit (200 ml) of AB0 compatible convalescent plasma during their treatment for COVID-19. Results: Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of Bcell lymphopenia (p=0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p=0.017), length of hospital stay (p=0.007), and PCR positivity (p=0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p<0.001) and hospital stay (p<0.0001). In those cases where there were at least ten days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p<0.001). Summary/Conclusion: Via combined administration of remdesivir and CP, we experienced an overwhelming survival rate in COVID-19 patients with hematological malignancies. Inhibition of viral replication with passive immunization proved to be efficient and safe. Our results suggest the clear benefit of early administration of CP to avoid protracted COVID-19 disease in patients with B-cell lymphopenia.
ABSTRACT
Background: Patients with lymphoproliferatie diseases (LPD) appear particularly ulnerable to SARS-CoV-2 infection, partly because of the effects of the anti-neoplastic regimens (chemotherapy, signaling pathway inhibitors, and monoclonal antibodies) on the immune system. The real impact of COVID-19 on the life expectancy of patients with different subtypes of lymphoma and targeted treatment is still unknown. Aims: The aim of this study is to describe and analyse the outcome of COVID-19 patients with underlying LPD treated with targeted drugs such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, niolumab or pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib), PI3K inhibitors (idelalisib), BCL2 inhibitors (enetoclax) and IMIDs, (lenalidomide). Methods: The surey was supported by EPICOVIDEHA registry. Adult patients with baseline CLL or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between January 2020 and January 2022 were selected. Results: The study included 368 patients (CLL n=205, 55.7%;NHL n=163, 44.3%) treated with targeted drugs (Table 1). Median follow-up was 70.5 days (range 19-159). Most used targeted drugs were ITKs (51.1%), anti-CD20 other than rituximab (16%), BCL2 inhibitors (7.3%) and lenalidomide (7.9%). Of note, only 16.0% of the patients were accinated with 2 or more doses of accine at the onset of COVID-19. Pulmonary symptoms were present at diagnosis in 244 patients (66.2%). Seere COVID-19 was obsered in 47.8 % patients while 21.7% were admitted to to intensie care unit (ICU), being 55 (26.8%) CLL patients and 25 (15.3%) NHL patients. More comorbidities were reported in patients with seere-critical COVID-19 compared to those with mild- asymptomatic infection (p=0.002). This difference was releant in patients with chronic heart diseases (p=0.005). Oerall, 134 patients (36.4%) died. Primary cause of death was COVID-19 in 92 patients (68.7%), LPD in 14 patients (10.4%), and a combination of both in 28 patients (20.9%).Mortality was 24.2% (89/368) at day 30 and 34.5%(127/368) at day 200. After a Cox multiariable regression age >75 years (p<0.001, HR 1.030), actie malignancy (p=0.011, HR 1.574) and admission to ICU (p<0.00, HR 4.624) were obsered as risk factors. Surial in patients admitted to ICU was 33.7% (LLC 38.1%, NHL 24%). Mortality rate decreased depending on accination status, being 34.2% in not accinated patients, 15.9-18% with one or two doses, decreasing to 9.7% in patients with booster dose (p<0.001). There was no difference in OS in NLH s CLL patients (p=0.344), nor in ITKs s no ITKs treated patients (p=0.987). Additionally, mortality rate dropped from the first semester 2020 (41.3%) to last semester 2021 (25%). Summary/Conclusion: - Our results confirm that patients with B--mallignancies treatted with targeted drugs hae a high risk off seere infection (47.8%) and mortality (36.4%) from COVID-19. - Pressence of comorbidities,, especially heart disease,, is a risk factor for seere COVIID--19 infection in ourr series. - Age >75 years,, actie mallignancy att COVIID--19 onset and ICU admission were mortality risk factors. - COVIID--19 acination was a protectie factor for mortality,, een iin this popullation wiitth humorall immunity impairment. - The learning cure in the management of the infection throughout the pandemiic and the deelopmentt off COVIID--19 treatments showed benefit in this partticullarlly ullnerablle popullation? (Table Presented).
ABSTRACT
Background: In most individuals, protective humoral and cellular immunity develops after two doses of the BNT162b2 Pfizer vaccine. In patients with lymphoma, humoral response is weaker and almost universally abrogated in patients who received anti-CD20 monoclonal antibodies. Whether cellular immune response is also abrogated is unknown. Aims: To determine whether patients with lymphoma develop specific T-cell mediated cellular response to BNT162b2 Pfizer vaccine. Methods: We included patients with lymphoma above the age of 18 years who received two doses of the BNT162b2 Pfizer vaccine and collected clinical and demographics data. T-cell immune response to the vaccine was analysed in patients' blood samples stimulated by spike antigen and quantified by two methods: (1) Interferon-gamma (IFNg)- release assay (IGRA, EuroImmun, Germany)- IFNg was quantified by ELISA (DuoSet, R and D Systems, Minneapolis, Minnesota, USA) and response above 50 pg/ml was considered positive. (2) Flow cytometry- Quantification of the T cell activation markers, CD134+ CD25+CD4+ T-cells was performed (Act-T4 CellTM kit, Cytognos, Spain), and any response above 0 was considered positive. Humoral response was measured by SARS-CoV-2 IgG II Quant (Abbott©) assay. The positive cut-off was set at 50AU/ml. Blood samples were drawn approximately 4 months after the second vaccination. Results: Sixty-nine lymphoma patients, treated with two vaccine doses, were included in this study. Median age was 66 (range: 30-84) and 39 (57%) were males. Sixty-two patients (90%) had non-Hodgkin lymphoma (NHL) including 18 with DLBCL, 26 with follicular lymphoma and 14 with marginal zone lymphoma. Seven (10%) patients had Hodgkin lymphoma. In this cohort, 70% (n=49) of the patients received anti CD20 MoAb, and 35% of them (n=27) were still on anti CD20 treatment. Thirteen patients received bendamustine-based immunochemotherapy. At the time of assessment (median 4.8 months after the 2nd vaccine) anti-spike antibodies were detected in only 42% (N = 29) of patients. In comparison, there was an increase in specific T cell response by any assay (IGRA and Flow) in 49% of patients (n = 34). The correlation between the IGRA and flow data was 0.7 (pearson correlation, P = 0.01). However, no correlation between humoral (qualitative and quantitative) and T cell response was shown, regardless of the assay applied. Cellular response was not corelated with the time elapsing from last immunochemotherapy. In the anti-CD20 MoAb treated cohort, of which 27 patients were still on active treatment at the time of vaccination, only 2 patients (7%) developed a humoral immune response, while cellular immunity was elicited in 52% (N = 15) patients (ELISA assay). In the Bendamustine treated cohort, with a median time from end of treatment to vaccination of 23 months (1-106 months), humoral but not cellular response correlated positively with the time from treatment completion to vaccination (p=0.04). Summary/Conclusion: The rate of cellular and humoral response to two doses of the BNT162b2 Pfizer vaccine in lymphoma patients was found to be significantly abrogated. In this small cohort, 49% of patients developed a cellular response despite a severely abrogated humoral immunity. These findings suggest that vaccine administration should be considered even early after anti CD20 therapy despite the reduced humoral immunity. These findings should be validated in studies with a higher number of patients.
ABSTRACT
Background: Prognosis of r/r B-NHL is detrimental. Potentially curative therapeutic approaches, such as autologous stem cell transplantation and innovative CAR-T cell therapy, require maximum disease control to achieve optimal results. Glofitamab is a new bispecific antibody, with a unique 2:1 molecular configuration resulting in superior potency compared with other CD20xCD3 bispecific antibodies with a 1:1 format. Aims: Based on these encouraging results, we included 5 heavily pretreated patients in the early access program of Glofitamab, available in our country. Methods: We collected the data of 5 consecutive patients with r/r B-NHL, who were treated with Glofitamab in our department during the last 15 months. Results: Three men and 2 women, median age of 57 years (38-62), were resistant to 4 (n = 3) and 5 (n = 2) previous lines of treatment. The underlying lymphoma was Richter's transformation of CLL after allogeneic transplantation (alloHSCT), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), r/r diffuse large B-cell lymphoma (DLBCL) after CAR-T therapy and gray zone lymphoma (GZL) transformed to DLBCL. The median number of Glofitamab cycles administered was 3 (2-7). All 5 patients responded early to treatment, which became apparent immediately after the first dose of 2.5 mg. The patient with Richter's syndrome achieved metabolic remission after the 4th cycle and underwent second alloHSCT after the 7th cycle. Unfortunately, he passed away 8 months after alloHSCT due to disseminated atypical mycobacterial infection, remaining however disease free. The patient with tFL also achieved metabolic remission, but the drug was discontinued after the 7th cycle due to COVID-19 infection. He died two months after Glofitamab interruption due to disease progression and CMV encephalitis. The patient with PMBCL, responded partially after Glofitamab and had mediastinal radiotherapy as bridging therapy to CAR-T therapy. As the latter was delayed due to CMV reactivation and CMV enteritis, our patient deceased due to progressive disease. The patient with DLBCL after CAR-T therapy had initial clinical response after two Glofitamab cycles. Due to severe COVID-19, we decided to hold Glofitamab. COVID-19 and disease progression led to his death, a few weeks after COVID-19 diagnosis. Finally, the patient with transformed GZL had Glofitamab administered as bridging therapy prior to CAR-T treatment. After 3 cycles, while she was prepared to proceed to CAR-T therapy, she was diagnosed with invasive aspergillosis. She is currently been treated with antifungal agents, whereas disease is still active. Cytokine release syndrome (CRS) occurred in 3 out of 5 patients. In all cases it was grade 1-2 and manifested at the first administration of the drug, after 4, 32 and 10 hours respectively, from infusion initiation. CRS was managed with antipyretics and steroids, whereas none patient required Intensive Care Unit support. Only one patient required tocilizumab. No Immune effector cell-Associated Neurotoxicity Syndrome (ICANS) was observed. Summary/Conclusion: Glofitamab is effective in treating patients with r/r aggressive B-cell NHL. Efficacy makes it an appropriate bridging tool to autologous, alloHSCT or CAR-T therapy. Nevertheless, relapse remains a challenge for r/r disease. Adverse events, such as CRS, were generally manageable. Given the fact that it was administered to heavily pretreated patients, caution to opportunistic pathogens should be paid. Indeed, toxicity profile may be proven to be more favorable if the agent is being administered earlier in therapeutic algorithms.
ABSTRACT
Background: Follicular lymphoma (FL) is a systemic neoplasm of the lymphoid tissue arising from B cell proliferation. The novel monoclonal anti-CD20 antibody obinutuzumab in combination with chemotherapy has been widely accepted as the first choice in front line treatment of FL. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19) is causing increased mortality among patients with lymphoproliferative disorders compared with the general population. Furthermore, there are some concerns in terms of morbidity and mortality for patients with FL because of their immunocompromised status induced by recent exposure to cytotoxic chemotherapy, especially bendamustine and anti-CD20. Aims: To investigate efficacy and safety of immunochemotherapy protocols for patients with newly diagnosed FL during COVID-19 pandemic. Methods: We retrospectively investigated medical data of all patients with newly diagnosed FL grade 1, 2 or 3A from Croatian hematologic registry in period from April 2019 to March 2021. Only patients which required systemic treatment were included in the analysis. All patients received obinutuzumab (G) in combination with either CHOP, bendamustine (B) or CVP chemotherapy protocol. Treatment response was evaluated using international lymphoma response criteria. Results: We analyzed a total of 114 FL patients treated with G-chemotherapy. Mean age was 62.4 ±10.5 years. Majority of patients were female (71/114 (62.3%)). FL grade I was present in 45/114 (39.5%), grade II in 28/114 (24.6%), grade III in 27/114 (23.7%) and not specified (but not IIIB) in 14/114 (12.3%) patients. A total of 61/114 (53.5%) patients were treated with G-B, 49/114 (43%) with G-CHOP and 4/114 (3.5%) with G-CVP immunochemotherapy. Similar rates of adverse events were observed in patients treated with G-CHOP and G-B Median follow up was 17 months. Overall response rate was 94%, complete remission (CR) in 68% and partial remission (PR) in 25% of patients. Median overall survival (OS) and progression free survival (PFS) were not reached with 12-months rates of 94% and 92%, respectively. Patients treated with G-CHOP had statistically significantly superior OS and PFS compared to patients treated with G-B (P=0.002 and P=0.006, respectively, Fig. 1). More favorable survival course associated with G-CHOP in comparison to G-B persisted in multivariate analysis (P=0,026, HR=15,12) after adjustment for age, sex, FLIPI grade and SARS-CoV-2 infection. Total of 12 patients died during the follow up and COVID-19 was cause of death in 5 patients. During the follow-up SARS-CoV-2 infection was diagnosed in 20/114 (17,5%) patients with overall mortality rate of 25%. All of the 7 patients treated with GCHOP recovered from SARS-CoV-2 infection and mortality rate in infected group of patients treated with G-B was 33% (4/12 patients). Image: Summary/Conclusion: Increased COVID-19 mortality in patients with lymphoproliferative disorders was observed in this study. Our group of patients had reduced OS and PFS compared to the GALLIUM trial and SARS-CoV-2 infection was the most pronounced risk factor for death. Even though in some studies bendamustine has shown to be less toxic and more effective than CHOP in FL, there are some important pandemic aspects that must be considered. Bendamustine exposure seems to be associated with worse outcome in case of the infection with SARS-CoV-2. These intriguing differences could play important role in treatment approach in COVID-19 pandemic. Future studies investigating hematological malignancies in COVID-19 pandemic are warranted.