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COVID-19 vaccine in patients with CLL
Figure 2. Correlation between neutralizing antibodies and COVID-19 IgG titer. NEUT Ab: neutralizing antibodies.
Of the 143 (38%) patients previously treated with anti- CD20 antibodies, only 38 (27%) responded to the vaccine and there was a significantly lower antibody response rate of only 5% in patients treated with anti-CD20 antibodies within the year of vaccination compared to 35% when the time from anti-CD20 therapy was more than 1 year (Table 3)
Analysis of the serological response in 106 patients treat- ed with BTK inhibitors revealed positive serological responses in 23% of the patients .There was a statistical dif- ference between the response rate in patients receiving ongoing BTK inhibitor therapy (18%) and that in previous- ly treated patients (37%). However, there was no statistical difference depending on whether the BTK inhibitor was given within 2 years or more than 2 years from the time of vaccination or depending on whether it was given as first- line therapy or in relapsed disease (Table 2, Figure 3B).
Sixty-two patients were treated with BCL2 inhibitors and of them 24% developed a positive serological response. Among those in whom BCL2 inhibition was combined with anti-CD20 antibodies only 14% developed a positive serological response. There was no statistical difference depending on whether patients received BCL2 inhibitor therapy within or more than a year before vaccination, or depending on whether the BCL2 inhibitor was given as first-line therapy or at relapse; however when the BCL3 inhibitor was combined with antiCD20 antibodies, vaccine response rates were lower.
Therapy with prophylactic intravenous immunoglobu- lins also correlated with vaccine response. Additional infor- mation is available in Table 2 and Figure 3B, C.
The effect of the vaccine on IgG levels
We compared IgG levels before and after vaccination. More specifically we compared IgG levels that were meas-
ured up to 150 days before the first dose of vaccine (when applicable) with the IgG levels of the corresponding patients at the serology test of this study and found that they were similar (mean levels: 768.89 mg/dL vs. 755.74 mg/dL, respectively).
A simple score to predict response to vaccine in individual patients with chronic lymphocytic leukemia
In addition to the multivariate logistic regression model, we generated a simple score based on seven factors (Figure 4): (i) anti-CD20 treatment in the 12 months preceding vac- cination (no: +30; yes: 0); (ii) treatment status (treatment- naïve: +10; previous or ongoing treatment: 0), (iii) age (<70 years. +10; ≥ 70 years: 0); (iv) IgM level (≥40 mg/dL: +10; <40 mg/dL: 0); (v) IgA level (≥80 mg/dL: +10; <80 mg/dL: 0), (vi) IgG level (≥700 mg/dL: +10; <700 mg/dL: 0), and (vii) hemoglobin concentration (normal [i.e., ≥13.5 g/dL for males and ≥12 g/dL for females]: +10; low: 0). All this infor- mation is readily available from the clinical history and a routine and affordable blood test.
The sum of all the above parameters in the scoring model can be used to estimate the probability of a given CLL patient developing sufficient antibodies after vacci- nation. For example, a 65-year-old (+10), pretreated (+0) patient but not with anti-CD20 in the preceding 12 months (+30) with normal IgA (+10), IgG (+10) and hemoglobin (+10) levels but abnormal IgM (+0) has a score of 70. i.e., a 70% probability of developing antibod- ies above the cutoff. Note that according to the model, the maximum score that can be obtained is 90 and not 100, highlighting the fact that even patients with the most favorable indicators are still at risk of not developing a response to vaccination. In the case that the value of a certain factor is missing, we redistribute its score among the other known factors according to their weights.
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