Immune Responses to SARS-CoV-2 Vaccination in Myelofibrosis Patients on JAK Inhibitors

Overview

Patients with myelofibrosis (MF) receiving JAK inhibitors exhibit severely impaired humoral and cellular immune responses to the standard two-dose SARS-CoV-2 vaccination schedule compared to healthy controls. A third mRNA vaccine dose improves immune responses, but patients on JAK inhibitors still show reduced neutralization capacity against both ancestral and Omicron BA.5 variants relative to those on alternative therapies.

Background

Myelofibrosis is a clonal myeloproliferative neoplasm characterized by fibrosis and inflammatory symptoms, often treated with JAK1/2 inhibitors such as ruxolitinib. These inhibitors impair cytokine signaling crucial for effective immune responses, increasing infection risk. Patients with advanced MF are at higher risk for severe COVID-19 and demonstrate impaired vaccine responses. The study assessed immune responses to SARS-CoV-2 vaccination in MF patients, particularly focusing on those receiving JAK inhibitors, in a setting with minimal natural SARS-CoV-2 exposure.

Data Highlights

Key Findings

• MF patients on JAK inhibitors had markedly reduced seroconversion rates (23.5%) after two vaccine doses compared to 100% in healthy controls.
• Spike-specific IgG antibody titers were significantly lower in MF patients on JAKi than in healthy controls (median ratio 0.40 vs 4.56, p < 0.0001).
• Cellular immunity measured by IFNγ ELISpot showed significantly fewer Spike-reactive T cells in MF patients on JAKi compared to controls (median 18.75 vs 458 SFU/10⁶ cells, p < 0.0001).
• A third mRNA vaccine dose increased antibody titers and T cell responses in MF patients, but those on JAKi still had lower responses than patients on alternative therapies.
• Neutralization capacity against both ancestral and Omicron BA.5 SARS-CoV-2 variants was reduced in MF patients on JAKi, even after the third vaccine dose.
• Patients on JAKi had more advanced disease features, including higher DIPSS+ scores and lower blood counts, which may contribute to impaired vaccine responses.

Clinical Implications

Clinicians should recognize that MF patients receiving JAK inhibitors have impaired immune responses to standard SARS-CoV-2 vaccination regimens, placing them at higher risk for COVID-19 despite vaccination. Additional vaccine doses and alternative protective strategies may be necessary to enhance immunity in this vulnerable population. Monitoring of both humoral and cellular immunity could guide personalized vaccination schedules and prophylactic interventions.

Conclusion

Myelofibrosis patients treated with JAK inhibitors demonstrate significantly diminished immune responses to SARS-CoV-2 vaccines, including reduced neutralization of variants. While booster doses improve immunity, these patients remain at increased risk and require tailored clinical management to optimize protection.

References

1. Harrison et al. 2022 -- Immune Responses to Ancestral and Omicron BA.5 SARS-CoV-2 Variants After Vaccination in Patients with Myelofibrosis