Efficacy and safety of tixagevimab‐cilgavimab versus SARS‐CoV‐2 breakthrough infection in the hematological conditions

Abstract

BackgroundManaging SARS‐CoV‐2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab‐cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real‐life data in a heterogeneous cohort are few.MethodsThe aim of this study is to evaluate the benefit of prophylaxis with tixagevimab‐cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch‐and‐wait strategy, followed in our center, during a median follow‐up of 249 (45‐325) days.ResultsAn incidence of 44 breakthrough infections (21.8%) is reported, with no treatment‐related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab‐cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti‐CD20 monoclonal antibodies and B–non‐Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred.ConclusionProphylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity.

Baseline IgM Amounts Can Identify Patients with Poor Outcomes: Results from a Real-Life Single-Center Study on Classical Hodgkin Lymphoma

“…Instead, as the side of acquired humoral immunity has been much less explored, one might ask if B cell aggregates can play an active role in intratumoral immunity or if they are mere bystanders in the HL microenvironment. Indeed, so-called immunoparesis, a condition that describes the suppression of uninvolved immunoglobulins, has been recently reported as a precursor marker of the absence of an immune response to the SARS-CoV-2 vaccine in lymphoproliferative disorders [31,32].…”

Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

“…131,132 As demonstrated, it may reduce the risk of severe infection and death in patients with breakthrough infections. 131,[133][134][135][136][137] However, recent Omicron variants might exhibit reduced sensitivity to tixagevimab/cilgavimab. [138][139][140]…”

“…Tixagevimab/cilgavimab was recommended for pre‐exposure prophylaxis during the COVID‐19 pandemic, particularly for patients within 1 year of CAR‐T therapy 131,132 . As demonstrated, it may reduce the risk of severe infection and death in patients with breakthrough infections 131,133–137 . However, recent Omicron variants might exhibit reduced sensitivity to tixagevimab/cilgavimab 138–140 …”

ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis

“…Ruxolitinib inhibits the hyperactivated JAK/STAT pathway and revolutionized management of MF patients by significantly reducing the spleen size, controlling constitutional symptoms, and prolonging survival; these benefits were demonstrated in the long-term analyses of the pivotal trials COMFORT-I and COMFORT-II [ 58 , 59 , 60 ], and global real-life studies [ 61 , 62 , 63 , 64 ]. Despite being tolerated very well, ruxolitinib is immunosuppressive, can precipitate opportunistic infections, alter cytokine responses [ 65 , 66 , 67 ], and may impair response to normal immune stimulation (e.g., SARS-CoV-2 vaccinations) [ 68 , 69 ]. Anemia is the most frequent reason leading to dose reduction/interruption of ruxolitinib in MF patients [ 70 ].…”