Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry

Abstract

Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.

Impact of Sars-CoV-2 prophylaxis with tixagevimab-cilgavimab in high-risk patients with B-cell malignancies: a single-center retrospective study.

“…In the EPICOVIDEHA registry, a matched-control cases analysis was performed, showing a 90% breakthrough infection rate, higher than in our study, with a comparable death rate, but with the limit of a small cohort (n=47) (Table 2). 12 In the present experience, no risk factors associated with severe COVID-19 or hospitalization, or death were identified, in contrast with our previous experience, which focused on the treatment of COVID-19 with MoAbs other than T-C, where the presence of comorbidity was associated with the risk of developing COVID-19 infection, and hospitalization and oxygen requirement were confirmed as prognostic factors for COVID-19 related death. 5 Similarly, as recently reported by Laracy et al in a large cohort of patients (n=892) including different hematological malignancies, there were no risk factors that allowed to foresee the infectious outcome in this setting except for the augmented schedule of T-C MoAb (Table 2).…”

“…9 However, recent studies, mainly performed in vitro, suggested inferior efficacy against omicron variants. [10][11][12] Our aim was to evaluate if this strategy's upcoming reported clinical benefit and safety to patients with hematologic malignancies were still in force in a reallife setting of high-risk hematologic patients during the omicron-predominant COVID-19 wave in Italy.…”

“…15 Real-life data are upcoming on the impact of preexposure prophylaxis in several hematological malignancies (e.g., hematopoietic stem cell transplantation, CAR-T cell patients, CLL), given the multiple factors involved in the clinical behavior of SARS-CoV-2, as shown in table 2. 10,12,14 A large recent Israelian retrospective experience highlighted a significant reduction in infection rate (3.5%) and mortality (0%) among immunocompromised patients receiving T-C MoAb versus no administration (Table 2). 11 Our study's breakthrough infection rate agreed with the data reported by Davis et al Patients with hematologic malignancies receiving T-C MoAbs (150/150 mg or 300/300 mg) experienced a confirmed COVID-19 breakthrough infection in 11% of cases (Table 2).…”

Survival in multiple myeloma and SARS‐COV‐2 infection through the COVID‐19 pandemic: Results from the EPICOVIDEHA registry

“…[24][25][26] On the other hand, studies would suggest that severity of disease and mortality rates are ameliorated also in this category of patients, mainly thanks to appropriate vaccination policies. 2,27 Furthermore, some preliminary, encouraging data, has been reported about preexposure prophylaxis with monoclonal antibodies against SARS-CoV-2 [28][29][30] and early start after SARS-CoV-2 infection with antiviral drugs 31,32 to prevent the progression to critical disease in severely immuno-compromised populations, such as MM patients.…”

Efficacy of Tixagevimab-Cilgavimab as Immunoprophylaxis in Patients With Hematologic Cancer

“…2 Only a few series to date have evaluated the efficacy of tixagevimab-cilgavimab as primary prophylaxis in patients with various HMTs, with conflicting results. [3][4][5] This cohort study aimed to compare the incidence and severity of COVID-19 among adult patients affected by HMTs who prophylactically received tixagevimab-cilgavimab and those who did not. From June 2022 to March 2023, Omicron variants were prevalent in Italy.…”