Ruxolitinib treatment in myelofibrosis and polycythemia vera causes suboptimal humoral immune response following standard and booster vaccination with BNT162b2 mRNA COVID-19 vaccine

Abstract

Patients affected by myelofibrosis (MF) or polycythemia vera (PV) and treated with ruxolitinib are at high risk for severe coronavirus disease 2019. Now a vaccine against the virus SARS-CoV-2, which is responsible for this disease, is available. However, sensitivity to vaccines is usually lower in these patients. Moreover, fragile patients were not included in large trials investigating the efficacy of vaccines. Thus, little is known about the efficacy of this approach in this group of patients. In this prospective single-center study, we evaluated 43 patients (30 MF patients and 13 with PV) receiving ruxolitinib as a treatment for their myeloproliferative disease. We measured anti-spike and anti-nucleocapsid IgG against SARS-CoV2 15-30 days after the second and the third BNT162b2 mRNA vaccine booster dose. Patients receiving ruxolitinib showed an impaired antibody response to complete vaccination (2 doses), as 32.5% of patients did not develop any response. After the third booster dose with Comirnaty, results slightly improved, as 80% of these patients produced antibodies above the threshold positivity. However, the quantity of produced antibodies was well below that reached than those reported for healthy individuals. PV patients elicited a better response than patients affected by MF. Thus, different strategies should be considered for this high-risk group of patients.

Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab

“…Our findings confirmed that a third mRNA vaccine failed to warrant long-term humoral immune responses against SARS-CoV-2 in the setting of patients treated with high dose of dexamethasone or undergoing continuous MM treatment (with monoclonal antibodies alone or associated with other drugs) or reporting a low value of IgM, as reported by our working group in different hematological diseases (e.g., patients affected by myelofibrosis) ( 11 ). In fact, after two months from the third dose, most of the vaccine’s non-responder patients at two doses did not show a stable anti-SARS-CoV-2 titer, highlighting even more the increased risk of mortality in these patients related to the infection, already known from the first evidence during the beginning of the pandemic ( 12 ).…”

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 ].…”

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

“…Malignancies (especially hematological), immunodeficiency states, and recent use of B‐cell–depleting therapies are well‐described clinical conditions capable of preventing an adequate vaccine response 3,4 . Several studies based on different hematological diseases were conducted to evaluate the ability of these patients to develop a protective level of antibody response, including by our group 5–7 …”

“…3,4 Several studies based on different hematological diseases were conducted to evaluate the ability of these patients to develop a protective level of antibody response, including by our group. [5][6][7] Furthermore, significant infection-related mortality besides receiving the vaccine in these subgroups of patients has been reported. On the other hand, the available new therapeutic strategies (e.g., monoclonal antibodies, antivirals) can limit the risk of worse outcomes.…”