Clinical Scorecard: Immune Responses to Ancestral and Omicron BA.5 SARS-CoV-2 Variants After Vaccination in Patients with Myelofibrosis
At a Glance
Category
Detail
Condition
Myelofibrosis (MF), a clonal myeloproliferative neoplasm with inflammatory manifestations
Key Mechanisms
Impaired immune responses due to JAK1/2 inhibitor (ruxolitinib) treatment affecting cytokine signalling and inflammatory response
Target Population
Adult patients with primary or secondary myelofibrosis receiving JAK inhibitors or alternative therapies
Care Setting
Outpatient vaccination and longitudinal observational study in clinical settings
Key Highlights
Patients with MF on JAK inhibitors show severely impaired humoral and cellular immune responses to two-dose COVID-19 vaccination compared to healthy controls.
Seroconversion rates after two vaccine doses were significantly lower in MF patients on JAK inhibitors (23.5%) versus healthy controls (100%).
Third vaccine dose with mRNA vaccines improved immune responses but differences persisted between patients on JAK inhibitors and those on alternative therapies.
Guideline-Based Recommendations
Diagnosis
Assess MF disease severity using clinical scores such as DIPSS+.
Monitor immune status in MF patients, especially those on JAK inhibitors, prior to and after vaccination.
Management
Prioritize early COVID-19 vaccination for MF patients, especially those receiving JAK inhibitors.
Administer two initial doses of viral vector-based vaccine (AZD1222) followed by a third mRNA vaccine dose (BNT162b2 or mRNA-1273) to enhance immunity.
Consider alternative therapies or supportive care for patients with advanced MF and impaired vaccine response.
Monitoring & Follow-up
Evaluate SARS-CoV-2 Spike-specific IgG titers and live virus neutralization capacity pre- and post-vaccination.
Assess T cell immunity via IFNγ ELISpot to determine cellular immune response.
Monitor for breakthrough infections and vaccine efficacy over time in MF patients.
Risks
Increased risk of infection including reactivation of latent viruses (e.g., varicella zoster, tuberculosis) in patients on JAK inhibitors.
Higher risk of severe COVID-19 and impaired vaccine response in advanced MF.
Potential reduced vaccine efficacy against emerging variants such as Omicron BA.5.
Patient & Prescribing Data
40 MF patients with median follow-up of 356 days; 24 on JAK inhibitors (ruxolitinib, momelotinib, fedratinib), 16 on hydroxyurea or no cytoreductive therapy.
JAK inhibitor-treated patients had advanced disease features and showed significantly reduced humoral and cellular responses to vaccination compared to those on alternative therapies and healthy controls.
Clinical Best Practices
Use a three-dose COVID-19 vaccination schedule including mRNA vaccines to improve immune responses in MF patients.
Closely monitor immune responses post-vaccination in MF patients, especially those on JAK inhibitors.
Adjust clinical management based on immune response data and disease severity to mitigate infection risk.
Maintain strict infection control and isolation measures where community transmission is low to protect vulnerable MF patients.
by Ahmad Alcheikh, Griffith B. Perkins, Phillippa A. Pucar, Amelia Cecchin, Cheng Sheng Chai, Matthew Tunbridge, Anouschka Akerman, Anupriya Aggarwal, Vanessa Milogiannakis, Stuart Turville, Sharon Allen, Pravin Hissaria, Tatjana Banovic, P. Toby Coates, David M. Ross
