Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies

Abstract

BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.CONCLUSIONSDose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

Seroconversion rate after vaccination against COVID-19 in patients with cancer—a systematic review

“…25,43 Overall, T-cell immune responses seem generally maintained, although reduced, especially in patients with hematologic malignancies, in comparison to patients with solid tumors and to healthy individuals, both after COVID-19 infection and after a complete vaccination, with predominance of CD4þ responses over CD8þ. 21,25,47,51,58 Systemic therapies did not have a major effect on cellular responses, except for higher suppression rates of CD4þ activity among patients treated with ICIs. 25 In the VOICE clinical trial, almost half of the vaccine non-responders and suboptimal responders to humoral immunity developed a Spike-specific T-cell response.…”

“…OCTAVE DUO trial). 51,68,76,78,[80][81][82][83][84] Furthermore, in the CAPTURE clinical trial, previous SARS-CoV-2 infection boosted vaccine-induced responses, lending further support for a third dose in vulnerable populations. 25 In line with these trends, many countries and institutions have already recommended that severely immunocompromised patients (e.g.…”

“…38 Similar results came from other recent reports, with a significant 14.2-fold increased risk of non-response to COVID-19 vaccination. 23,50,51 Finally, serologic responses are also impaired in certain populations with MM receiving therapies against CD38 (e.g. daratumumab, isatuximab) and B-cell maturation antigen (anti-BCMA agents, e.g.…”

Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position article

“…In the oncology field, three studies with currently available data evaluated the impact of early D3 vaccine injection in poor humoral responders’ patients with LM ( 42 ), with thoracic cancer ( 35 ) and in allogenic transplanted patients in remission of a HM ( 43 ). Nevertheless, these studies employed different serological assays rendering data comparison rather difficult, unless using the conversion factors proposed by the World Health Organization (WHO) (NIBSC code 20/136).…”

“…In the first study, Re et al, while using Roche Elecsys assay, demonstrated that LM patients with positive anti-S Abs titers after D2 similarly exhibited increased neutralizing antibodies (Nabs), with a > 80% correlation between Nabs levels and anti-S Abs titers above > 400 BAU/mL ( 42 ). In patients with multiple myeloma, the median anti-S Abs titer prior to D3 was 100 BAU/mL, rising to 2700 BAU/mL (p <0.0001) thereafter, which is comparable to anti-S Abs serum levels from vaccinated healthy donors 6 to 8 weeks after D2 ( 7 ), using the same technique.…”