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1.
Jpn J Infect Dis ; 75(6): 608-611, 2022 Nov 22.
Article in English | MEDLINE | ID: covidwho-2145167

ABSTRACT

Immunocompromised patients are more likely to develop severe COVID-19, and exhibit high mortality. It is also hypothesized that chronic infection in these patients can be a risk factor for developing new variants. We describe a patient with prolonged active infection of COVID-19 who became infected during treatment with an anti-CD20 antibody (obinutuzumab) for follicular lymphoma. This patient had persistent RT-PCR positivity and live virus isolation for nine months despite treatment with remdesivir and other potential antiviral therapies. The computed tomography image of the chest showed that the viral pneumonia repeatedly appeared and disappeared in different lobes, as if a new infection had occurred continuously. The patient's SARS-CoV-2 antibody titer was negative throughout the illness, even after two doses of the BNT162b2 mRNA vaccine were administered in the seventh month of infection. A combination of monoclonal antibody therapy against COVID-19 (casirivimab and imdevimab) and antivirals resulted in negative RT-PCR results, and the virus was no longer isolated. The patient was clinically cured. During the 9-month active infection period, no fixed mutations in the spike (S) protein were detected, and the in vitro susceptibility to remdesivir was retained. Therapeutic administration of anti-SARS-CoV-2 monoclonal antibodies is essential in immunocompromised patients. Therefore, measures to prevent resistance against these key drugs are urgently needed.


Subject(s)
COVID-19 , Lymphoma, Follicular , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/pathology , COVID-19/drug therapy , BNT162 Vaccine , SARS-CoV-2 , Antibodies, Viral
3.
Intern Med ; 61(16): 2523-2526, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1993647

ABSTRACT

A patient with follicular lymphoma treated with obinutuzumab and bendamustine experienced prolonged coronavirus disease-2019 (COVID-19). One month after the symptoms transiently improved, the patient experienced exacerbated COVID-19 symptoms. The patient recovered from COVID-19 with remdesivir and dexamethasone and was discharged 77 days after the disease onset. The patient completed a primary series of SARS-CoV-2 vaccinations on day 176, but the anti-spike protein IgG was not detected later. A careful observation to detect any subsequent relapse of COVID-19 symptoms is necessary in immunocompromised patients. Chemotherapy should be based on the disease status and type of lymphoma.


Subject(s)
COVID-19 , Lymphoma, Follicular , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride/therapeutic use , Humans , Immunocompromised Host , Lymphoma, Follicular/complications , Lymphoma, Follicular/drug therapy , Rituximab/therapeutic use , SARS-CoV-2
4.
Clin Lymphoma Myeloma Leuk ; 22(8): e730-e737, 2022 08.
Article in English | MEDLINE | ID: covidwho-1966439

ABSTRACT

INTRODUCTION: Chimeric antigen receptor T-cell therapy (CAR T) is a revolutionary adoptive immunotherapy approach in lymphoma; however, substantial resources are necessary for administration and care of these patients. Our institution has administered tisagenlecleucel primarily in an outpatient setting, and here we report our clinical outcomes. PATIENTS AND METHODS: We conducted a single institution, retrospective study investigating outcomes of adult lymphoma patients treated with commercial tisagenlecleucel between 10/2017 and 12/2020. We analyzed patient characteristics and outcomes of efficacy and safety including overall response rate, progression-free survival, overall survival and cytokine-release syndrome, neurotoxicity, and hospitalizations. RESULTS: Seventy-two patients with relapsed or refractory non-Hodgkin lymphoma (NHL) who received commercial tisagenlecleucel were identified; 68 (94.4%) patients received outpatient tisagenlecleucel. The overall response rate was 43% with a complete response observed in 25 patients (34.7%). At a median follow-up of 9.1 months, the median progression-free survival was 3.3 months. Grade 3-4 cytokine release syndrome was not observed in the study group and two patients had grade 3-4 neurotoxicity. Twenty-six patients (36.1%) were admitted within 30 days after infusion with a median length of stay of 5 days. Fourteen patients (19.4%) were admitted within 72 hours of infusion. No patient died of CAR T cell-related toxicity. CONCLUSION: Our experience affirms treatment with tisagenlecleucel in the outpatient setting is safe and feasible with close supervision and adequate institutional experience. After infusion, adverse events were manageable and the majority of patients did not require hospitalization.


Subject(s)
Lymphoma, Follicular , Receptors, Antigen, T-Cell , Adult , Antigens, CD19 , Cytokines , Humans , Immunotherapy, Adoptive , Lymphoma, Follicular/drug therapy , Retrospective Studies
5.
Acta Haematol ; 145(4): 384-393, 2022.
Article in English | MEDLINE | ID: covidwho-1538008

ABSTRACT

INTRODUCTION: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying hematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of 5 patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. METHODS: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids, and convalescent plasma in 5 patients with FL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistent infection. Reverse transcriptase polymerase chain reaction tests and peripheral blood immunophenotype were performed for all patients. RESULTS: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13-42) from the previous discharge. They all showed B-cell depletion by immunophenotyping, and no traces of immunoglobulin antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. CONCLUSION: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed FL patients treated with ICT.


Subject(s)
COVID-19 , Lymphoma, Follicular , COVID-19/complications , COVID-19/therapy , Humans , Immunization, Passive , Immunocompromised Host , Lymphoma, Follicular/complications , Lymphoma, Follicular/drug therapy , Recurrence , SARS-CoV-2
6.
Clin Lymphoma Myeloma Leuk ; 21(10): e810-e816, 2021 10.
Article in English | MEDLINE | ID: covidwho-1313014

ABSTRACT

BACKGROUND: We previously reported elsewhere of a follicular lymphoma patient suffering from persistent COVID-19 pneumonia that was still ongoing at 2 months after onset. MATERIALS AND METHODS: We provide a follow-up report of the case along with a literature review of immunocompromised lymphoma patients experiencing prolonged COVID-19 infections. RESULTS: Although requiring a full 1 year, the presented case eventually achieved spontaneous resolution of COVID-19 pneumonia. Anti-SARS-CoV-2 antibodies could not be detected throughout the disease course, but COVID-19-directed T-cell response was found to be intact. The patient also developed secondary immune thrombocytopenia subsequent to COVID-19 pneumonia. We found 19 case reports of immunocompromised lymphoma patients with prolonged COVID-19 infections in the literature. All 5 patients who died did not receive convalescent plasma therapy, whereas resolution of COVID-19 infection was achieved in 8 out of 9 patients who received convalescent plasma therapy. CONCLUSIONS: We demonstrate through the presented case that while time-consuming, resolution of COVID-19 infections may be achieved without aid from humoral immunity if cellular immunity is intact. Immunocompromised lymphoma patients are at risk of a prolonged disease course of COVID-19, and convalescent plasma therapy may be a promising approach in such patients.


Subject(s)
COVID-19/immunology , Lymphoma, Follicular/drug therapy , Pneumonia/immunology , Rituximab/therapeutic use , SARS-CoV-2/immunology , Thrombocytopenia/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/virology , Female , Follow-Up Studies , Humans , Immunocompromised Host/immunology , Lymphoma, Follicular/complications , Lymphoma, Follicular/immunology , Maintenance Chemotherapy/methods , Middle Aged , Pneumonia/complications , Pneumonia/virology , Remission, Spontaneous , SARS-CoV-2/physiology , T-Lymphocytes/immunology , T-Lymphocytes/virology , Thrombocytopenia/complications
7.
Blood ; 139(11): 1631-1641, 2022 03 17.
Article in English | MEDLINE | ID: covidwho-1309901

ABSTRACT

18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is now established as the gold-standard imaging modality for both staging and response assessment in follicular lymphoma (FL). In this Perspective, we propose where PET can, and cannot, guide clinicians in their therapeutic approach. PET at diagnosis and pretreatment is important for staging, with greater sensitivity compared with standard CT, and consequent improved outcomes in truly limited-stage FL. Small data sets suggesting that a high baseline standardized uptake value (SUVmax) identifies de novo histologic transformation (HT) have not been corroborated by data from GALLIUM, the largest prospective study to examine modern therapies for FL. Nonetheless, the role of baseline quantitative PET measures requires further clarification. The median survival of patients with newly diagnosed FL is now potentially >20 years. Treatment of symptomatic FL aims to achieve remission and optimize quality of life for as long as possible, with many patients achieving a "functional cure" at the cost of unwanted treatment effects. Several studies have identified end-of-induction (EOI) PET after initial chemoimmunotherapy in patients with a high tumor burden as strongly predictive of both progression-free and overall survival, and EOI PET is being evaluated as a platform for response-adapted treatment. Unmet needs remain: improving the inferior survival for patients remaining PET positive and quantifying the progression-free survival and time to next treatment advantage, and additional toxicity of anti-CD20 maintenance in patients who achieve complete metabolic remission. In the absence of an overall survival advantage for frontline antibody maintenance, the question of using PET to guide the therapeutic approach is more important than ever in the context of the COVID-19 pandemic.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorodeoxyglucose F18 , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/drug therapy , Positron Emission Tomography Computed Tomography/methods , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Humans , Kaplan-Meier Estimate , Outcome Assessment, Health Care/methods , Pandemics , Prednisone/administration & dosage , Prospective Studies , Rituximab/administration & dosage , SARS-CoV-2/physiology , Vincristine/administration & dosage
8.
Viruses ; 13(7)2021 06 23.
Article in English | MEDLINE | ID: covidwho-1289015

ABSTRACT

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient's family. Current decisions to take revolve around patient's follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.


Subject(s)
Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19/complications , Humans , Immunity, Humoral , Lymphocyte Depletion , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/therapy , Male , Middle Aged , SARS-CoV-2/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
9.
Monaldi Arch Chest Dis ; 91(4)2021 Jun 10.
Article in English | MEDLINE | ID: covidwho-1268373

ABSTRACT

Covid-19 in immunocompromised patients shows a prolonged course and may lead to a poor prognosis. Although data on hyperimmune plasma for treatment of Covid-19 suggest an improved outcome in immunocompetent patients, limited data are currently available in immunocompromised patients. We present the case of a 62-year-old Caucasian woman, who was previously treated with obinutuzumab and bendamustine for follicular lymphoma and showed a prolonged positive test for Covid-19. Since no improvement was observed with standard of care (including remdesivir), the possibility of hyperimmune plasma infusion was discussed. A first dose of hyperimmune plasma was administered, with subsequent onset of fever, increasing inflammatory indexes and worsening radiological findings. Three days later a second dose of plasma was administered. Within twelve hours cough and fever disappeared, and oxygen at rest was discontinued. The patient was discharged 5 days later, and nasopharyngeal swabs resulted negative 16 days after discharge.


Subject(s)
COVID-19 , Lymphoma, Follicular , Female , Humans , Immunocompromised Host , Lymphoma, Follicular/drug therapy , Middle Aged , SARS-CoV-2 , Treatment Outcome
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