ABSTRACT
Hematological malignancies (HMs) have heterogeneous serological responses after vaccination due to disease or treatment. The aim of this real-world study was to analyze it after Pfizer-BioNT162b2 mRNA vaccination in 216 patients followed up for 1 year. The first 43 patients had an initial follow-up by a telemedicine (TM) system with no major events reported. The anti-spike IgG antibodies were checked 3-4 weeks post-first vaccination and every 3-4 months, by two standard bioassays and a rapid serological test (RST). Vaccine boosts were given when the level was <7 BAU/mL. Patients who did not seroconvert after 3-4 doses received tixagevimab/cilgavimab (TC). Fifteen results were discordant between two standard bioassays. Good agreement was observed between the standard and RST in 97 samples. After two doses, 68% were seroconverted (median = 59 BAU/mL) with a median of 162 BAU/mL and 9 BAU/mL, respectively, in untreated and treated patients (p < 0.001), particularly for patients receiving rituximab. Patients with gammaglobulin levels < 5 g/L had reduced seroconversion compared to higher levels (p = 0.019). The median levels were 228 BAU/mL post-second dose if seroconverted post-first and second, or if seroconverted only post-second dose. A total of 68% of post-second dose negative patients were post-third dose positive. A total of 16% received TC, six with non-severe symptomatic COVID-19 within 15-40 days. Personalized serological follow-up should apply particularly to patients with HMs.
ABSTRACT
Pts with HM may have low or delayed specific immune response after usual vaccination due to immune deficiency, associated to the disease or to the therapy. In this real-life study, 235 pts vaccinated with BNTCV (BioNTech Pfizer) were monitored for 2 years, starting 06/20 in a single Institution. Patients ’population and follow-up. 235 patients including 225 with HM initially received 2 doses of BNTCV (IM) with 3 weeks between the 2 first doses, including 98 lymphomas (L), 28 monoclonal gammopathies with undetermined significance (MGUS), 34 multiple myelomas (MM), 34 myeloproliferative disorders (MPD), 27 chronic lymphocytic leukemias (CLL), 4 acute leukemias and 10 non-malignant hemopathies. The first 43 pts had initial follow-up by telemedicine system connecting the pt to the Institute, developed by La Valeriane Inc. (Montpellier, France), 24/24h, 7 days. Seroconversion was assessed by analyzing IgG anti-Spike protein antibody (AcAS) every 3-4 weeks after the first vaccination and then, every 3-4 months, by SARS-CoV-2 IgG II Quant® Assay (Abbott, France) and Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, France), in duplicate with the 2 assays, by 2 independent labs. Additional boosts of vaccine were administered in case of seronegativity or when the level of antibody was <7 BAU/mL. Pts not seroconverted after 4-5 doses of vaccine received tixagevimab/cilgavimab (EVUSHELD®, AstraZeneca). Tolerance using telemedicine application. Local pain (<1 day) was common and transient, particularly after the 2nd dose. 4/43 pts reported significant adverse events through telemedicine, followed by a medical call, including severe asthenia for ≥2 days, fever (>38°C) for at least 2 days, headache, or general pain. The satisfaction survey of monitoring system was good. Adherence to vaccination was excellent (only one refusal/235 pts). AcAS follow-up 15 Results were discordant (12 with Abbott +, Roche -, and 3 with Abbott - Roche +). Semi-quantitative rapid test (BIOSIS HEALING, Beijing China) was compared to Abbott with good concordance on 97 samples. After 2 doses of BNTCV, 72% of the pts were seroconverted, (median, range) (59, 3-319) BAU/mL, Abbott), including 62% CLL (121), 66% L (39), 91% MGUS (204), 61% MM (15) and 81% SMD (50). 50% of the pts receiving daratumumab (median 8 BAU/mL, 1-20) and only 38% of the pts receiving rituximab (median 0, 0-20) were seroconverted, as compared to 71% of the pts receiving other treatment or 80% (42, 2-210) with no therapy (161, 29-637) (p<0.001). Low gammaglobulin levels (<5g/L, p=0.019), similarly to the IgG level were associated with reduced seroconversion. Median levels of AcAS were 1679 BAU/mL post 2nd dose if seroconverted after the 1st dose and 308 if seronconverted only post 2nd dose. 68% of the pts negative after the 2nd dose were positive after the 3rd dose. 16 pts received tixagevimab/cilgavimab, 6 having symptomatic non-severe COVID-19 in the 15-40 days after the injection. There is a need to follow AcAS (including with rapid test) for pts having HM after BNTCV to adapt vaccine strategy including boosts or EVUSHELD. The usage of telemedicine connecting system may help to follow the early tolerance and to improve the pts’ adherence.