A new study published in Blood Cancer Journal has revealed severe impairment of humoral and cellular vaccine responses in patients with myelofibrosis (MF), suggesting the JAK1/2 inhibitor (JAKi) use as a modifiable predictor of insufficient protection against the SARS-CoV-2 strains. The study observed a consistent increase in antibody titer for the JAKi cohort with repeated vaccination, suggesting that further booster dosing might help overcome this impaired response.
The researchers conducted a longitudinal observational study of vaccine response in adult patients with primary or secondary MF receiving a JAKi. Patients with MF were prioritized for early vaccination, and most participants received 2 initial doses of the AZD1222 (University of Oxford/ AstraZeneca) vaccine followed by a third dose of either BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna/NAIAD).
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Participants provided samples before and after vaccine doses at various time points, and immune responses were compared to those of 10 healthy controls. The MF study group was adjusted to include individuals receiving additional therapies after being advised on a third dose of the vaccination.
Study results showed that patients receiving JAKi exhibited advanced disease features (including lower platelet and hemoglobin counts and higher LDH) compared to those with alternative therapies. Moreover, patients with MF receiving JAKi had severely impaired humoral and cellular immune responses to the initial 2-dose vaccination schedule compared to healthy individuals. In contrast, MF patients receiving alternative therapies had improved serologic responses.
The results also indicated that only a few patients, before the third (mRNA- platform) dose on the JAKi therapy, seroconverted compared to patients with MF on alternative therapies. Furthermore, the third dose significantly increased the median antiSpike IgG titers in both groups. However, the titers were lower in patients receiving a JAKi than in other therapies. Additionally, no improvement was seen in T-cell response with the addition of a third dose in both groups.
“We suggest patients on a JAKi be included among at-risk groups considered for access to prophylactic measures currently in development to protect against current and future viral strains,” the authors highlighted.
Myelofibrosis is a clonal myeloproliferative neoplasm linked with multiple inflammatory symptoms, including fibrosis and constitutional ones. The primary treatment for symptomatic MF is ruxolitinib, a JAKi antagonizing cytokine receptor signaling. While JAK-dependent cytokine signals are key to an effective inflammatory response, ruxolitinib treatment is associated with an increased risk of infection, including tuberculosis and the reactivation of the varicella-zoster virus.
Prior studies have reported that individuals with advanced MF have a greater risk of severe COVID-19 and impaired response to the vaccination, the researchers noted. Understanding the effectiveness of COVID-19 vaccines has been challenging, but research has shown that serological neutralization of the live virus can correlate with real-world protection, they added.
Moreover, the emergence of new SARS-CoV-2 variants that can bypass vaccine-induced immunity has highlighted the importance of T cells in fighting the virus, the study team said. High levels of CD8+ T cells are associated with improved COVID-19 outcomes in patients with hematological malignancies despite the reduced levels of virus-neutralizing antibodies, they continued.
Reference
Alcheikh A, Perkins GB, Pucar PA, et al. Humoral and cellular immunity to SARS-CoV-2 ancestral and omicron BA.5 variants following vaccination in myelofibrosis patients. Blood Cancer J. Published online Apr 10, 2023. doi:10.1038/s41408-023-00824-8
