Page 161 - 2022_03-Haematologica-web

Response to BNT162b2 vaccine in lymphoma patients
common treatment protocols included CHOP (cyclophos- phamide, vincristine, adriamycin and prednisone) or ben- damustine with or without anti-CD20 monoclonal anti- bodies, either rituximab or obinutuzumab. Few patients received other therapies, such as Bruton tyrosine kinase (BTK) inhibitors, lenalidomide or antiPD1 antibodies. The patients’ characteristics are presented in Table 1.
Serological response to vaccination
Eighty-three patients (51%) were seropositive (IgG levels ≥50 AU/mL) and 49% had negative serology. In univariate
analysis, the following variables were found to be signifi- cantly associated with a lack of serological response: age >80 years (OR=4.3, 95% CI: 1.1-1.6), absolute lymphocyte count <1.2x109/L (OR=2.3, 95% CI: 1.1-4.4), IgG levels <630 g/L (OR=15.8, 95% CI: 1.9-129.9), active disease (defined as being under treatment for remission induction or by a positive positron emission tomography/computed tomography result) at vaccination (OR=4.2, 95% CI: 2.1- 8.2), a time period of <12 months between the last anti- CD20 treatment and vaccination (OR=31.3, 95% CI: 8.4- 116.9), the use of obinutuzumab versus rituximab (OR >4.54), aggressive non-Hodgkin lymphoma versus Hodgkin lymphoma (OR=15.4, 95% CI: 3.1-76.6) (Table 2). Lack of seroconversion was most frequent among patients suffering from aggressive lymphoma (63%) followed by those with indolent lymphoma (54%) and was lowest in patients with Hodgkin disease (10%). With the negative response rate in the last group used as a reference, the OR of this variable for patients with indolent disease was 1.5 (not statistically sig- nificant), while it was as high as 15 for patients with aggres- sive lymphoma (statistically significant, P<0.01). The rates of negative serological responses in patients receiving CHOP relative to those treated with bendamustine, with or without anti-CD20 monoclonal antibodies, were 63% and 84%, respectively (P=0.056). In multivariate analysis, two variables remained statistically significant: a time period <12 months between the last anti-CD20 treatment and the second dose of vaccine, and presence of active lymphoma (Table 3).
The effect of anti-CD20 treatment on vaccination results
Among 98 patients who received anti-CD20 monoclonal antibodies, as the time period between the last dose of this treatment and vaccination became longer, the likelihood of seropositivity increased. The seropositivity rate was 80% in patients vaccinated at least 12 months after administration
Table 2. Univariate analysis of factors associated with a lack of serological response.
Table 1. Characteristics of the patients with lymphoma. Characteristics
Age in years, median (IQR) Males
Comorbidities
Diabetes mellitus
Ischemic heart disease
Hypertension
Chronic renal failure
Chronic obstructive pulmonary disease Other malignancy
Type of lymphoma
Diffuse large B-cell lymphoma Follicular lymphoma
Marginal zone lymphoma Hodgkin lymphoma Peripheral T-cell lymphoma Other lymphomas*
Line of treatment
Watch & wait
First line
Second line
Third line and beyond
Type of treatment
Non-chemotherapy
Anti-CD20 monoclonal antibodies Rituximab
Obinutuzumab
Anti-PD1 monoclonal antibodies BTK inhibitors
Lenalidomide
Chemotherapy
CHOP Bendamustine ABVD/BEACOPP COP
Other treatments**
N (%)
65 (52-73) 89 (55%)
30 (19%) 17 (11%) 54 (34%) 12 (7.5%) 7 (4%) 27 (17%)
32 64 24 20 8 14
30 89 20 23
98 (60%) 68
30
5 (3.5%) 4 (3%) 6 (4%)
36 (25%) 32 (22%) 10 (7%) 9 (6%) 19 (13%)
Variable
Age ≥80 years
Gender: female
ALC ≤1.2 x109/L
IgG ≤630 g/L
Active disease
Time between the last anti-CD20 treatment and vaccination <12 months
Type of anti-CD20 MoAb: obinutuzumab
Type of lymphoma – indolent lymphoma*
Aggressive lymphoma**
Time between the last chemotherapy administration and vaccination: <19 days
Reference (95% CI)
Age < 80 years
Male
ALC >1.2 G/L
IgG >630 g/L
Disease in remission
>12 months or non-exposure to anti-CD20
Rituximab
Hodgkin lymphoma Hodgkin lymphoma
>19 days
Odds ratio
4.3 (1.1-1.6) 0.8 (0.42-1.5) 2.3 (1.1-4.4) 15.8 (1.9-129.9) 4.2 (2.1-8.2) 31.3 (8.4-116.9)
>4.54 (NA)
1.46 (0.67-3.1) 15.4 (3.1-76.6)
1.75 (0.32-9.4)
P-value 0.031
0.9 0.02 0.001 <0.001 <0.001
0.04
0.34 <0.01
0.515
*Other lymphomas:Waldenström macroglobulinemia,mantle cell lymphoma,primary mediastinal B-cell lymphoma. **Other treatments: platinum-based chemotherapy, gemcitabine, brentuximab vedotin, polatuzumab vedotin, pralatrexate, romidepsin, phosphoinositide 3-kinase inhibitors. IQR: interquartile range; PD-1: programmed death; BTK: Bruton tyrosine kinase; CHOP: cyclophosphamide, adriamycin, vincristine and prednisone; ABVD: adriamycin, bleomycin, vinblastine and dacarbazine; BEA- COPP: bleomycin, etopside, adriamycin, cyclophosphamide, vinblastine, procarbazine and prednisone; COP: cyclophosphamide, vincristine and prednisone.
*Indolent lymphoma included follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma and Waldenström macroglobulinemia. **Aggressive lymphoma included diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma and peripheral T-cell lym- phoma. 95% CI: 95% confidence interval; ALC: absolute lymphocyte count; NA: not applicable; MoAb: monoclonal antibody.
haematologica | 2022; 107(3)
717