Responses to mRNA SARS-CoV-2 vaccines in patients with MPN: Findings from two studies

Vaccination against SARS-CoV-2, particularly with spike protein messenger ribonucleic acid (mRNA) vaccines, has proved highly effective against symptomatic COVID-19 infections. However, outcomes and responses to mRNA vaccines in patients with hematologic malignancies are not well studied.^1,2

The MPN Hub has previously reported on the incidence, mortality, and thrombotic events associated with SARS-CoV-2 in patients with MPN. Here we present the findings from two recent studies: one by Cattaneo et al.¹ published in the Blood Cancer Journal, reporting a single center experience of the impact of diagnosis and treatment on responses to mRNA SARS-CoV-2 vaccines in patients with BCR-ABL1-negative MPN; and another study by Kozak et al.² published in Leukemia, investigating the responses to mRNA SARS-CoV-2 vaccines in patients with Philadelphia-chromosome (Ph)-positive or -negative MPN.

Impact of diagnosis and treatment on response to mRNA vaccines¹

This was a single center, prospective study conducted in Milan, Italy, in patients with MPN receiving mRNA SARS-CoV-2 vaccine between March and June 2021. Moderna or Pfizer-BioNTech were the two types of vaccines administered in patients. After a median time of 5.3 weeks from second vaccine dose, anti-spike and anti-nucleocapside immunoglobulin (Ig) G titer were assessed. Patients above cutoff level (0.4 U/mL), based on each antibody type according to manufacturer’s instructions, were considered ‘responders’, and those below the cutoff level as ‘non-responders’ to the vaccine.

Results

Baseline characteristics

A total of 62 patients were included and the baseline characteristics are summarized in Table 1.

Table 1. Baseline characteristics*

ET, essential thrombocythemia; MF, myelofibrosis; MPN-U, myeloproliferative neoplasm, unclassifiable; mRNA, messenger ribonucleic acid; PMF, primary myelofibrosis; PV, polycythemia vera; SMF, secondary myelofibrosis. *Adapted from Cattaneo et al.1
Characteristic, % unless otherwise stated	Total (N = 62)
Median age at vaccination, years (range)	71.9 (33.7–86.3)
Median time from MPN diagnosis to vaccination, years (range)	9.7 (0.1–36.2)
Median time from start of ongoing treatment to vaccination, years (range)	3.1 (0.1–18.5)
Diagnosis
PV	34
ET	18
MF	42
PMF	24
SMF	18
MPN-U	7
Cytoreductive therapy at vaccination
Hydroxyurea	24
Anagrelide	5
Interferon	7
Givinostat	5
Ruxolitinib	48
Median daily dose (mg) of ruxolitinib, (range)	20 (10–40)
Vaccine type
BNT162b2 (Pfizer-BioNTech)	36
mRNA-1273 (Moderna)	65

Responses

• 22.6% of patients did not have a detectable anti-spike level (< 0.4 U/mL).
• 6.5% showed positive anti-nucleocapside antibodies, with three patients reporting a previous SARS-CoV-2 infection.
  • Two of the four patients had myelofibrosis (MF), three were vaccinated with Pfizer-BioNTech and one with Moderna vaccine.
  • All seroconversion for anti-spike occurred with a high titer.
• Responder rate or the level of antibody titers did not show difference between the two vaccines.
• The response to mRNA vaccine was negatively associated with MF diagnosis (p = 0.002) and ruxolitinib therapy (p = 0.05) compared with other MPN diagnosis and other treatments.
  • Patients with MF who were either taking or not taking ruxolitinib showed a lower response to vaccines (p = 0.07 vs 0.03). The findings remained consistent in the multivariable analysis (p = 0.03).
  • Responses were similar between ruxolitinib-treated patients in both the MF subgroup (p = 0.50) and in other MPN patients (p = 0.25), suggesting a confounding by indication.
  • Neither the time from MPN diagnosis to vaccination nor time from start of ongoing therapy to vaccination had any impact on vaccine responses.
• In univariate analysis, older age, MF diagnosis, ruxolitinib therapy, and short time (< 3 years) from start of ongoing therapy to vaccination were associated with lower anti-spike levels.  This association was confirmed with MF diagnosis (p = 0.002) and ruxolitinib (p = 0.005) in multiple regression model.
• No adverse events were reported except fever or pain at the injection site.

Conclusion

This study demonstrated that the rate of seroconversion to mRNA SARS-CoV-2 vaccines was lower (77.4%) in patients with MPN compared to healthy adults and patients, with patients with MF showing the worst outcomes (< 60%). The median anti-spike titers were adversely affected by treatment with ruxolitinib in responders; however, the cause was not known. The authors suggest that healthcare professionals should encourage patients with MPN, particularly MF with or without treatment with ruxolitinib, to be cautious and take protective measures against COVID-19 even after vaccination.  

Responses to mRNA SARS-CoV-2 vaccines²

This was a retrospective cohort study in patients with MPN receiving two doses of mRNA BNT162b2 (Pfizer) or mRNA-1273 (Moderna). Patients with chronic myeloid leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), or blast-phase MPN (MPN-BP) were eligible. Serological testing was performed and considered positive ≥ 50 AU/mL.

Results

Baseline characteristics

A total of 74 patients (median age of 68.2 years) were included and the median time from last dose of vaccination to measurement of serum antibody response was 100 days.

• The cohort consisted of 22 patients with CML, 14 with ET, 14 with PV, 22 with MF, and two patients with MPN-BP (transformed from prior post-ET MF).
• All patients except four of the 22 CML patients and 11 of the 22 MF patients were not receiving active treatments.

Responses

There was antibody seropositivity observed in all disease categories but no significant differences among MPN subtypes. However, of note, the following were observed:

• In the ET cohort, spike protein antibody levels were higher (mean 4,151.15 AU/mL) in patients treated with pegylated interferon compared to patients treated with hydroxyurea (mean 2,368.62 AU/mL) or aspirin only (2,447.52 AU/mL).
• There was no difference in spike protein antibody levels between patient with PV receiving or not receiving cytoreductive therapy.
• Lower levels of spike protein antibody were observed in the MF cohort when comparing patients on ruxolitinib (mean 603.1 AU/mL) vs those under observation (mean 6,353.29 AU/mL), but the difference was not statistically significant.
  • In patients with spike protein antibody levels available for serial assessment, six of the seven patients showed a reduction in antibody level from time of initial assessment. The mean level of decrease in antibody level was 67% at a median of 6 months from completion of their initial vaccination.
• Responses were assessed in 13 patients who received a third or booster dose of mRNA vaccine at a median of 6.8 months from completion of their initial vaccination; there was a 200% increase in the spike protein antibody level.
• Only three patients, one with CML on ponatinib, one with PV on ruxolitinib, and one with MPN-BP on ruxolitinib did not have measurable antibody response to vaccination.

Conclusion

This study demonstrated that patients with MPN receiving two doses of mRNA SARS-CoV-2 vaccine showed high rate of seroconversion including those treated with cytoreductive therapies. Antibody levels achieved appeared to decrease over time; however, a booster dose was able to increase them in most patients. The findings should be interpreted with the caveats that the sample size was relatively small to determine potential distinct differences between MPN-directed treatments within each disease subgroup. Further research with a larger cohort and extended follow-up period is therefore warranted.