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COVID-19 vaccine in patients with CLL
Table 3. Response to the BNT162b2 mRNA COVID-19 vaccine based on laboratory and genetic parameters.
Variable
del17p, n (%) No
Yes
del11q, n (%) No
Yes
del13q, n (%) No
Yes
trisomy 12, n (%) No
Yes
TP53 mutation, n (%) No
Yes
IGHV, n (%) Mutated Unmutated
WBC (x109/L) ≤100x109/L, n (%) >100x109/L, n (%)
Hemoglobin, mg/dL Normal, n (%) Low, n (%)
Platelets, x109/L Normal, n (%) Low, n (%)
ANC, x109/L ≥1,500 <1,500
IgG, mg/dL
≥700 mg/dL, n (%) <700 mg/dL, n (%)
IgM, mg/dL
≥40 mg/dL, n (%) <40 mg/dL, n (%)
IgA, mg/dL
≥80 mg/dL, n (%) <80 mg/dL, n (%)
Monoclonal protein, n (%) No
Yes
Serologic response Positive
n=160 (43%)
75 (33%) 9 (30%)
70 (33%) 14 (32%)
49 (33%) 28 (29%)
65 (35%) 10 (19%)
28 (29%) 3 (43%)
19 (40%) 27 (32%)
13.5 154 (44%) 6 (24%)
13.6 116 (51%) 44 (30%)
179 104 (51%) 53 (33%)
3.8 119 (43%) 32 (41%)
844 88 (47%) 37 (28%)
46.8 76 (57%) 43 (26%)
109 81 (51%) 42 (29%)
67 (45%)
10 (45%)
Total Odds ratio (95% CI)
n=373
226 1 (ref)
30 0.86 (0.38-1.98)
211 1 (ref)
44 0.94 (0.47-1.89)
148 1 (ref)
95 0.84 (0.48-1.48)
188 1 (ref)
52 0.45 (0.21-0.96)
97 1 (ref)
7 1.85 (0.39-8.8)
48 1 (ref)
84 0.72 (0.35-1.51)
348 1 (ref)
25 0.4 (0.16-1.02)
226 1 (ref)
147 0.41 (0.26-0.63)
205 1 (ref)
163 0.47 (0.31-0.72)
275 1 (ref)
79 0.89 (0.54-1.48)
187 1 (ref)
130 0.45 (0.28-0.72)
134 1 (ref)
166 0.27 (0.16-0.43)
159 1 (ref)
147 0.39 (0.24-0.62)
150 1 (ref)
22 1.03 (0.42-2.54)
P-value
0.727
0.8617
0.5524
0.0346
0.4345
0.3881 0.086
0.0481 0.002
<0.001 <0.001
0.0004 0.754
0.6613 0.001
<0.001 < 0.001
<10-5 < 0.001
<0.001 0.9447
Negative n=213 (57%)
151 (67%) 21 (70%)
141 (67%) 30 (68%)
99 (67%) 67 (71%)
123 (65%) 42 (81%)
69 (71%) 4 (57%)
29 (60%) 57 (68%)
10.8 194 (56%) 19 (76%)
13.055 110 (49%) 103 (70%)
145 101 (49%) 110 (67%)
3.355 156 (57%) 47 (59%)
709 99 (53%) 93 (72%)
24.7
58 (43%) 123 (74%)
65
78 (49%) 105 (71%)
83 (55%)
12 (55%)
95% CI: 95% confidence interval, del: deletion; WBC: white blood cell count; ANC: absolute neutrophil count..
Contrariwise, an ineffective response was more frequently seen in older patients (not as reported in the healthy popu- lation2) who had received several lines of prior therapies.
We also report the negative effect of ongoing therapy with novel anti-CLL agents on the immune response to the vaccine. In our cohort there were 79 and 34 patients receiv- ing ongoing therapy with BTK inhibitors and BCL2 inhibitors, respectively, and less than 20% of them had a response to the vaccine. In addition, our findings also sup- port the observations recorded by others in earlier studies regarding the development of B-cell depletion and late B- cell reconstitution following anti-CD20 antibody treat- ment.15 In our cohort we noted in particular that patients who had been treated with anti-CD20 antibodies in the 12 months preceding vaccination had a clearly much lower
response and only 5% responded effectively to the vaccine. Recently, Herishanu et al.16 reported that the humoral immune response to BNT162b2 mRNA COVID-19 vaccine in 167 patients with CLL from a single center was 39.5%. Similar to our results, response to the vaccine was markedly impaired and was affected by prior treatment status and the
type of therapy given.
Our study documents real-world experience in a large
cohort of patients and, for the first time, also examined neu- tralizing antibodies following vaccination in patients with CLL. This is important because, as recently reported by Garcia-Beltran et al., SARS-CoV-2 neutralizing antibodies predict the severity of COVID-19 and survival.22
While the results reported here are mostly in accor- dance with previously published observations,21 in our
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