2287P - Multiomic Biological mOdifications in the immune response of patients treated with chemotherapy, anti-CD20, or immune-checkpoint inhibitors and receiving a Third dose of vaccinE against SARS-CoV-2 (the BO0STER study)

Background

Antibody titers after two doses of mRNA-based SARS-Cov-2 vaccines (SVC) decline after 6 months, requiring a further dose to boost immune response. Anticancer agents may differentially impact the response to SVC, but a direct comparison between patients and with healthy controls (HC) has not been conducted. We serially assessed the immunomic changes associated with the booster dose of SVC in patients treated with adjuvant chemotherapy (aCT, colorectal and breast cancer), rituximab (R, non-Hodgkin lymphoma), immune checkpoint inhibitors (ICI, solid tumors), and HC.

Methods

In the above mentioned groups, we performed blood transcriptome sequencing (TS), multiplex antibody titer (ABt, Spherotech), and SARS-CoV-2-specific IFN release assay (IGRA) before the third vaccine dose (TS/AT/IGRA), after 24 hours (TS), at 5 days (d - TS/IGRA), 26d (AT/IGRA) and after six months (mo - AT/IGRA). Immune transcriptomic modules were assessed using BloodGene3.

Results

We enrolled 52 subjects: 11 R, 11 ICI, 8 aCT, and 22 HC. aCT or ICI showed similar vaccine-specific ABt compared with HC at 26d, increasing at 6mo. ICI showed a significantly reduced increase of IgG2 vaccine-specific ABt at 26d compared with HC. R showed a blunted response at 26d. In all groups, the Env and Core ABt increased significantly at 6mo (81% of subjects), with symptomatic infection in only 31% of subjects. We observed a delayed (5d) but efficient increase in inflammation and chemochine modules in aCT, reduced early inflammation (24h) and increased delayed plasma-cell response (5d) in ICI, and reduced response to all immune modules, except for a delayed increase in IFN modules (5d), in R compared with HC. IGRA results were consistent with IFN modules, with a 5d increase in R.

Conclusions

Patients undergoing aCT and ICI mount a vaccine-mediated immunomic response in part similar, but not identical, to HC, and R patients show a blunted vaccine response in line with the literature. A large fraction of all enrolled subjects developed ABt against natural infection, in the absence of symptoms, at 6mo.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

IRCCS Policlinico San Martino, Genoa IT.

Funding

University of Genoa , 5x1000 IRCCS funds, AIRC, ACC.

Disclosure

G. Zoppoli: Financial Interests, Personal, Stocks or ownership: Immunomica Srl; Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Institutional, Product Samples: ThermoFisher Scientific; Non-Financial Interests, Personal, Other, Travel grant: Novartis, Roche. C. Genova: Financial Interests, Personal, Invited Speaker, Speaker's Bureau (scientific meeting): AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Eli Lilly, Novartis; Financial Interests, Personal, Advisory Board, Advisory board: Amgen, Sanofi; Financial Interests, Personal, Advisory Board, Advisory Board: Roche, Takeda; Financial Interests, Institutional, Funding, Funding for support of translational study: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Funding in support of translational study: AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant for translational study: Italian Ministry of Health; Non-Financial Interests, Principal Investigator, Local PI for clinical trials: AstraZeneca, Roche; Non-Financial Interests, Member, Scientific Society Membership: ASCO, AIOM, FONICAP, AIOT, IASLC, ISLB. R. Lemoli: Financial Interests, Other: Jazz, Pfizer, AbbVie, BMS, Sanofi, StemLine. All other authors have declared no conflicts of interest.