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1872 Severe COVID-19 Infection in Patients with Chronic Lymphocytic Leukemia or Indolent B-Cell Non-Hodgkin Lymphoma Who Received Pre-Exposure Prophylaxis with Tixagevimab and Cilgavimab in Italy: Preliminary Results of the Observational Study By the Gimema Working Party on Chronic Lymphoproliferative Disorders and By the Fondazione Italiana Linfomi

Program: Oral and Poster Abstracts
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, CLL, Lymphomas, Clinical Research, Diseases, Real-world evidence, Lymphoid Malignancies, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Gian Matteo Rigolin1*, Antonio Urso2*, Stefano Soddu3*, Riccardo Moia, MD4*, Riccardo Dondolin, MD5*, Attilio Olivieri6*, Ilaria Scortechini7*, Annamaria Frustaci8*, Marina Deodato, MD8*, Giulia Daghia2*, Francesca Romana Mauro, MD9*, Sara Pepe, MD, PhD10*, Marina Motta, MD11*, Antonella Anastasia12*, Lydia Scarfo, MD13, Emanuela Sant'Antonio13*, Pellegrino Musto14*, Annamaria Giordano, MD15*, Andrea Mengarelli16*, Martina Tomassi17*, Sara Martinelli18*, Caterina Patti, MD19*, Marika Porrazzo, MD19*, Alessandro Sanna, MD20*, Rossella Riccioni21*, Clara Virginia Vigano'22*, Francesca Paola Paoloni3*, Alfonso Piciocchi, MS3*, Paola Fazi3*, Guido Gini, MD23, Andrés José María Ferreri, MD24, Paolo Ghia, MD, PhD13 and Antonio Cuneo, MD2*

1Hematology Section, St. Anna University Hospital, Ferrara, Italy
2Ematologia, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy
3GIMEMA Foundation, Rome, Italy
4Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
5Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, ITA
6Hematology Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
7Clinica di Ematologia ospedali riuniti diAncona, Università Politecnica delle Marche, Ancona, Italy
8Dipartimento di Ematologia, ASST Grande Ospedale Metropolitano Niguarda, Niguarda Cancer Center, Milan, Italy, Milano, Italy
9Hematology, Department of Translational and Precision Medicine, Sapienza University, Roma, Italy
10Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
11Hematology, ASST Spedali Civili di Brescia, Brescia, Italy
12S.C. Ematologia, ASST Spedali Civili di Brescia, Brescia, Italy
13Laboratory of B-cell Neoplasia Strategic Research Program on CLL Division of Experimental Oncology IRCCS Ospedale San Raffaele, Milan, Italy
14Department of Precision and Regenerative Medicine and Ionian Area, "Aldo Moro" University School of Medicine,and Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, Bari, Bari, Italy
15Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico,  and Department of Precision and Regenerative Medicine and  Ionian Area, "Aldo Moro" University School of Medicine, Bari, Italy, Bari, Italy
16Hematology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Roma, ITA
17Hematology and Stem Cell Transplant Unit, IRCCS - Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (I.F.O.), Rome, Italy
18Struttura Semplice Dipartimentale di Ematologia Ospedale S. Chiara Trento, Trento, ITA
19U.O.C. di Oncoematologia, "Ospedali Riuniti Villa Sofia - Cervello (Presidio V. Cervello), Palermo, Italy
20Hematology, AOU Careggi, Florence, Italy
21UOC Ematologia ATNO, Ospedale di Livorno, Livorno, ITA
22Dipartimento Oncologico, ASST Lecco Ospedale Manzoni, Unità semplice di Oncoematologia, Lecco, Italy
23Hematology Unit, AOU delle Marche-Università Politecnica delle Marche, Ancona, Italy
24Unit of Lymphoid Malignancies, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milano, Italy

Patients with chronic lymphocytic leukemia (CLL) or indolent B-cell non-Hodgkin lymphoma (iB-NHL) are at risk of developing severe COVID-19 infection, with a high mortality rate in the pre-vaccination era (18%-30%). These patients respond poorly to vaccination, especially those receiving anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhibitors (BTKi) or the BCL2 inhibitor venetoclax. Pre-exposure prophylaxis (PrEP) with the neutralizing antibodies tixagevimab and cilgavimab drastically reduced the incidence of symptomatic COVID-19 infection in subjects with a higher chance of an inadequate response to vaccination against SARS-CoV-2. Therefore, we designed this observational study with the primary objective to describe the incidence of severe COVID-19 infection (COVID-19-related hospitalization or COVID-19 related death) in patients with CLL or iB-NHL (follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma) who received PrEP with tixagevimab and cilgavimab (NCT05803395). Each patient had a minimum follow-up of 6 months from the first PrEP dose.

Overall, 513 patients (CLL n=343, iB-NHL n= 170) aged ≥ 18 years who received the study drug as per label between March and October 2022 were included in the present study. Ninety-nine% of patients received PrEP with tixagevimab and cilgavimab at a dosage of 300 mg as per approved indications in Italy. Key baseline characteristics were: median age 72 years (range 33-94), Male/Female 62%/38%, ECOG performance status ≤ 2 96%, one or more comorbidities 69%, advanced stage (Ann Arbor 3-4, Binet B-C) 62%. Forty-one% of the patients had received more than one previous line of therapy, 73% were on anti CLL/NHL treatment at the time of PrEP administration and 25% of them had received previous treatment with anti-CD20 monoclonal antibodies. Ninety-eight% of the patients had received previous anti COVID-19 vaccination and 26% of the cases had a previous COVID infection.

At 6 months from PrEP, 159/513 patients (31%) had a COVID-19 infection and 39% of these patients received an anti-viral treatment with nirmatrelvir/ritonavir or remdesivir. The 6-month rate of severe infections was 3.5% (18/513, 12 CLL, 6 B-iNHL). The median time between PrEP and severe infection was 3.35 months, (IQR 1.85, 4.68). Overall, 50% of the patients with severe infection required oxygen therapy, with intensive care hospitalization in 22% of the cases and a COVID-related death in 22% (n=4). At 6 months, the overall COVID-19 related mortality rate among all patients who had an infection was 2.5%. Patients with severe infection were older as compared with patients with mild infection (75 vs 71 years p=0.014). A diagnosis of B-iNHL or CLL, the presence of comorbidities, previous or ongoing treatment, previous COVID-19 vaccination or previous COVID-19 infection had no impact on the risk of severe COVID. Noteworthy, 17/18 cases of severe COVID infection occurred in a period (August 2022-January 2023) in which the Omicron sub-variants BA.5 and BQ.1 were prevalent in Italy.

In conclusion, in this population of CLL and iB-NHL at high risk for poor response to vaccination, the modern management strategy that included PrEP with tixagevimab and cilgavimab and treatment with antiviral drugs resulted in low rates of severe COVID infection and death.

Funding: the study was supported by an unconditional grant from AstraZeneca S.p.A.

Disclosures: Rigolin: Janssen: Honoraria, Other: support for attending meetings, Speakers Bureau; BeiGene: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau. Mauro: AstraZenca SpA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Scarfo: Octapharma: Honoraria; Janssen: Honoraria; Lilly: Honoraria; BeiGene: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria. Musto: Grifols: Honoraria; Incyte: Honoraria; Johnson & Johnson: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Sobi: Honoraria; Takeda: Honoraria; Glaxo-Smith-Kline: Honoraria; Gilead: Honoraria; Bristol-Myers Squibb: Honoraria; Bei-Gene: Honoraria; Astra-Zeneca: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Alexion: Honoraria; Abbvie: Honoraria. Piciocchi: Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Gedeon Richter: Honoraria; Pharming: Honoraria; Takeda: Honoraria. Ghia: BeiGen: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Johnson&Johnson: Consultancy, Research Funding; Galapagos: Consultancy; Loxo@Lilly: Consultancy; MSD: Consultancy; Galapagos: Consultancy; AstraZeneca: Consultancy, Research Funding; AbbvVie: Consultancy, Research Funding; Roche: Consultancy. Cuneo: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings.

*signifies non-member of ASH