470. Relapsing COVID-19 Pneumonia in Patients Receiving Rituximab Therapy

Background Rituximab is a monoclonal antibody against the CD20 antigen on B-lymphocytes leading to B-cell death and depletion. Patients who receive rituximab and are infected with the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) causing coronavirus disease (COVID-19) may have increased difficultly clearing the virus and be at risk for persistent disease. While the limited literature available is mixed regarding the severity of COVID-19 in patients receiving rituximab, there is minimal literature regarding persistent and relapsing COVID-19 in this patient population. This is a case series of patients with persistent COVID-19 who previously received rituximab. Methods This is a retrospective review of 5 patients admitted between 1/1/2021 and 5/1/2021 to our institution with confirmed COVID-19 and receipt of rituximab for any indication within the previous 12 months. Information regarding hospital readmissions, time course of positive infection, medical management, disease severity, and discharge disposition were collected. Results Five patients, median age of 46, currently or recently on rituximab therapy were admitted a median of 2 times due to persistent, severe COVID-19 (Table 1). Patients received their initial COVID-19 diagnosis a median of 34 days (8-102 days) since their last rituximab administration and had documented SARS-CoV-2 infection a median of 66 days (19-195 days; Figure 1). All 5 patients received remdesivir and corticosteroids over the course of their COVID-19 disease and 2 patients received convalescent plasma therapy 1 and 5 days prior to a positive SARS-CoV-2 antibody IgG. Figure 1. Patient SARS-CoV-2 Infection Course Table 1. Patient Clinical and Therapeutic Data Conclusion Rituximab therapy may be associated with persistent or relapsing COVID-19 disease. Controlled investigations are necessary to evaluate the exact impact anti-CD20 agents have on the course of COVID-19 and whether convalescent plasma or other therapies can prevent relapsing disease. Disclosures All Authors: No reported disclosures

Dengue fever in a multiple sclerosis patient taking Ocrelizumab

Dengue fever (DF) is an endemic infectious disease in tropical and subtropical regions. Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen on B cells, which is approved for the treatment of both relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS). We describe the favorable clinical outcome of DF in an RRMS patient treated with Ocrelizumab, who neither presented hemorrhagic or systemic shock symptoms nor reported neurological worsening.

Use of rituximab in paediatric nephrology

Rituximab is a chimeric monoclonal antibody capable of depleting B cell populations by targeting the CD20 antigen expressed on the cell surface. Its use in oncology, initially in B cell lymphoma and post-transplant lymphoproliferative disorders, predates its current utility in various fields of medicine wherein it has become one of the safest and most effective antibody-based therapies. It was subsequently found to be effective for rheumatological conditions such as rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Over the past decade, rituximab has generated a lot of interest in nephrology and has become an emerging or accepted therapy for multiple renal conditions, including systemic lupus erythematosus, lupus nephritis, vasculitis, nephrotic syndrome and in different scenarios before and after kidney transplantation. This review outlines its current use in paediatric nephrology practice, focusing on the knowledge required for general paediatricians who may be caring for children prescribed this medication and reviewing them on a shared care basis.

Hydrogen Deuterium Exchange Mass Spectrometry identifies the dominant paratope in CD20 antigen binding to the NCD1.2 monoclonal antibody

A comparative canine-human therapeutics model is being developed in B-cell lymphoma through the generation of a hybridoma cell that produces a murine monoclonal antibody specific for canine CD20. The hybridoma cell produces two light chains, light chain-3, and light chain-7. However, the contribution of either light chain to the authentic full-length hybridoma derived IgG is undefined. Mass spectrometry was used to identify only one of the two light chains, light chain-7, as predominating in the full-length IgG. Gene synthesis created a recombinant murine-canine chimeric monoclonal antibody expressing light chain-7 that reconstituted the IgG binding to CD20. Using light chain-7 as a reference sequence, hydrogen-deuterium exchange mass spectrometry was used to identify the dominant CDR region implicated in CD20 antigen binding. Early in the deuteration reaction, the CD20 antigen suppressed deuteration at CDR3 (VH). In later time points, deuterium suppression occurred at CDR2 (VH) and CDR2 (VL), with the maintenance of the CDR3 (VH) interaction. These data suggest that CDR3 (VH) functions as the dominant antigen docking motif and that antibody aggregation is induced at later time points after antigen binding. These approaches define a methodology for fine mapping of CDR contacts using nested enzymatic reactions and hydrogen-deuterium exchange mass spectrometry. These data support the further development of an engineered, synthetic canine-murine monoclonal antibody, focused on CDR3 (VH), for use as a canine lymphoma therapeutic that mimics the human-murine chimeric anti-CD20 antibody Rituximab.

Ocrelizumab-induced alopecia areata—A series of five patients from Ontario, Canada: A case report

Background: Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen found on B-cells. It is indicated in the treatment of both relapsing–remitting multiple sclerosis and primary progressive multiple sclerosis. Objective: The aim of this study is to report and describe the characteristics of alopecia areata following treatment with ocrelizumab for multiple sclerosis. Results: Five patients were reported, two female and three male. Four of the five patients had alopecia areata of the scalp, one of the five having alopecia to the beard area. All patients responded well to conventional treatment with topical and intralesional corticosteroids and topical minoxidil foam. Ocrelizumab can be associated with the development of alopecia areata. Initiation of proper treatment may lead to quick improvement or resolution of this potentially reversible adverse effect.

The use of rituximab in the treatment of disimmune polyneuropathy: a description of clinical cases and a literature review

Dysimmune neuropathies are heterogeneous group of acquired immune-mediated diseases, accompanied by damage to the peripheral nervous system. As a standard therapy, prednisolone and intravenous immunoglobulins are used. Also encouraging efficacy is demonstrated by the use of a genetically engineered chimeric monoclonal antibody to the CD20 antigen found on the surface of normal and malignant B-cells – rituximab. Rituximab shows encouraging results. We reviewed the use of rituximab for dysimmune polyneuropathies and described our experience in administration of Lewis–Sumner syndrome and myelin-associated glycoprotein related neuropathy with rituximab.

Rituximab-Induced Acute Thrombocytopenia in a Patient with Relapsed Follicular Lymphoma

Introduction Rituximab is a well-tolerated monoclonal antibody which is commonly used in the treatment of B cell lymphomas that bear CD20 antigen. Most of the adverse effect induced by rituximab are infusion-related symptoms. Rituximab-induced acute thrombocytopenia (RIAT) are rare than other side-effects such as serum sickness-like syndrome and most of the reports are described as case reports. Here, we reported a serious acute thrombocytopenia caused by rituximab in a refractory and relapsed (R/R) follicular lymphoma (FL) patient with massive tumor burden. To our knowledge, this is the third case that we can retrieve Methods A 56-year-old woman was enrolled in our ward in 2011. The patient was diagnosed as FL (grade 2, stage IV, group B, IPI score 2) and received three cycles of R-CHOP without rituximab-associated serum sickness or obvious evidence of bone marrow toxicity. A partial response (PR) was achieved but the patient rejected to receive further therapy. She had experienced night sweats, fatigue, and floating during the preceding 7 months and came to the clinic in April 2018. Physical examination found multiple sites of shallow lymphadenopathy, especially in her right neck. The spleen was 7.5 cm palpable below the left costal margin and the ascites sign was positive. Re-biopsy was done in her right neck lymph node and FL (grade 3a) was confirmed again by IHC. The routine blood test showed WBC of 2,710, neut 1,100, Hb 90 g/L, and platelets count of 84. The bone marrow biopsy showed lymphocytic cells infiltration. So the diagnosis of the relapsed FL (grade 3a, stage IV, group B, FLIPI-1 Score 4) was made. We chose R-CHOP regimen again and rituximab was administrated at day 0 with a dose of 600mg. She developed shiver and fever one hour after the rituximab infusion. Blood culture showed no bacteria growth and inflammation index has no positive result. On the next day, repeat hemogram showed a platelet count of 26,000. The coagulation profile was within normal limits. The patient didn't show any sign of bleeding and did not meet the threshold criteria for platelet transfusion. On the third day post-rituximab infusion, the platelet count was 45,000 and recovered to baseline of the platelets level within one week. She had a similar episode during the following treatment contained rituximab (one cycle of R-CHOP and two cycles of R-GDP). No more intervention was given and the platelet count recovered again within one week. After two cycles of R-GDP, no obvious response was achieved and the patient died of progression of the disease. Results We conducted a literature review about RIAT. It is a rare adverse event and usually occurs within 1 to 3 days after rituximab infusion. Most of the patients with RIAT share the common clinical characteristics: MCL was the predominant histological subtype; many patients present infusion-associated symptoms; they often had comorbidity of massive tumor burden, bone marrow infiltration, and splenomegaly; re-exposure to rituximab usually will not induce a repetitive RIAT but there are exceptions; RIAT is s usually transient and self-limiting. Compared to MCL, RIAT in FL is not a frequent adverse event. To the best of our knowledge, we only found two recent reports associated RIAT developed in patients with FL reported by Japanese researchers. The possible mechanisms of RIAT remain unclear and they might lie in the following ways: 1. The presence of CD20 antigen on the platelets themselves can lead to the antibody-mediated cell lysis through Fc receptors. 2. The patient had soluble CD20 antigen in the circulation, binding them to platelets causing immune-mediated cell lysis. 3. The splenomegaly also contributed to the delay and the destruction of platelets. 4. With a rapid lysis of lymphoma cells and changes in the levels of cytokines and complements, thrombocytopenia can be initiated by the induction of a disseminated intravascular coagulation. 5. P38 mitogen-activated protein kinase and Akt anti-apoptotic survival pathways might play important roles in leading to cell death. Conclusion Here we reported a patient diagnosed as R/R FL with a massive tumor burden developed repetitive and self-recovered RIAT. Massive tumor burden, bone marrow infiltration, and splenomegaly might be risk factors to develop a RIAT. Hence, rituximab should be used with caution in patients who have these factors, and routine blood count monitoring should be considered after the administration of rituximab. Disclosures No relevant conflicts of interest to declare.