{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:35:59Z","timestamp":1793414159101,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>messenger RNA (mRNA)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines such as BNT162b2 became available in late 2020, but hematological malignancy patients (HM pts) were not evaluated in initial registration trials. We hereby report the results of a prospective, unicentric, observational study Response to COVID-19 Vaccination in hEmatological malignancies (CERVAX) developed to assess the postvaccine serological and T-cell-mediated response in a cohort of SARS-CoV2-negative HM pts vaccinated with BNT162b2. Patients with lymphomas [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], chronic lymphocytic leukemia (CLL), and multiple myeloma (MM); off-therapy for at least 3 months; in a watch-and-wait program; or in treatment with ibrutinib, venetoclax, and lenalidomide were included. Different time points were considered to assess the serological response to the vaccine: before the second dose (T1), at 3\u20136\u201312 months after the first dose (T2\u20133\u20134, respectively). Since March 2021, 39 pts have been enrolled: 15 (38%) NHL, 12 (31%) CLL, and 12 (31%) MM. There were 13 of the 39 pts (33%) seroconverted at T1; an increase of the serological response was registered after the second dose (T2) (22\/39 pts, 56%) and maintained after 6 months (22\/39 pts, 56%) and 12 months (24\/39 pts, 61%) from the first dose (T3\u2013T4, respectively). Non-serological responders at T4 were 7\/39 (18%): 0\/15 NHL, 1\/12 MM (8%), and 6\/12 CLL (50%). All of them were on therapy (one lenalidomide, three ibrutinib, and three venetoclax). SARS-CoV2-reactive T-cell analysis (interferon gamma release assays) was available since June 2022 and was evaluated at 12 months (T4) from the first dose of vaccine in 31\/39 pts (79%). T-cell-mediated-responders were 17\/31 (55%): most of them were NHL and MM (47%, 41% and 12% for NHL, MM, and CLL, respectively). Both serological and T-cell non-responders were represented by pts on active therapy (venetoclax\/ibrutinib). During the period of observation, eight (20.5%) pts developed mild SARS-CoV2 infection; no coronavirus disease 19 (COVID-19)-related deaths or hospitalizations were registered. In conclusion, in our cohort of lymphoproliferative pts receiving BNT162b2, CLL diagnosis and venetoclax\/ibrutinib seem to be related with a lower humoral or T-mediated response. Nevertheless, the efficacy of mRNA vaccine in HM pts and the importance to continue the vaccine program even in non-responders after the first dose are supported in our study by demonstrating that a humoral and T-cell-mediated seroconversion should be observed even in the subsets of heavily immunocompromised pts.<\/jats:p>","DOI":"10.3389\/fonc.2023.1133348","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T06:31:38Z","timestamp":1677479498000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study \u201cCervax\u201d"],"prefix":"10.3389","volume":"13","author":[{"given":"Sara","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Lucchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sirianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Porrazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ballotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Ballerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Maria","family":"De Sabbata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"De Bellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cappuccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Granzotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Toffoletto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Fortunati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Russignan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia Elzbieta","family":"Florea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Torelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30251-9","article-title":"Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: A retrospective, multicentre, cohort study","volume":"7","author":"Passamonti","year":"2020","journal-title":"Lancet Haematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008824","article-title":"Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients","volume":"136","author":"Vijenthira","year":"2020","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101765","article-title":"BNT162 mRNA covid-19 vaccine in a nationwide mass vaccination setting","volume":"384","author":"Dagan","year":"2021","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30601-7","article-title":"Vaccination of patients with hematological malignancies who did not have transplantations: Guidelines from the 2017 European conference on infections in leukemia (ECIL 7)","volume":"19","author":"Mikulska","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2016.044","article-title":"Influenza and pneumococcal vaccination in hematological malignancies: A systematic review of efficacy, effectiveness, and safety","volume":"8","author":"La Torre","year":"2016","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00213-8","article-title":"Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: Interim analysis of a prospective observational study","volume":"22","author":"Monin","year":"2021","journal-title":"Lancet Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011904","article-title":"Low neutralizing antibody responses against SARS-CoV-2 in older patients with myeloma after the first BNT162b2 vaccine dose","volume":"137","author":"Terpos","year":"2021","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.09.002","article-title":"Evaluation of Abbott anti-SARS-CoV-2 CMIA IgG and euroimmun ELISA IgG\/IgA assays in a clinical lab","volume":"510","author":"Manalac","year":"2020","journal-title":"Clin Chim Acta"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc3103","article-title":"A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations","volume":"12","author":"Grzelak","year":"2020","journal-title":"Sci Transl Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.1038\/s41467-020-18468-8","article-title":"SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood","volume":"11","author":"Ng","year":"2020","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02005-20","article-title":"Serological assays estimate highly variable SARS-CoV-2 neutralizing antibody activity in recovered COVID19 patients","volume":"58","author":"Luchsinger","year":"2020","journal-title":"J Clin Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1537","article-title":"Interferon-gamma release assay for accurate detection of severe acute respiratory syndrome coronavirus 2 T-cell response","volume":"73","author":"Murugesan","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014124","article-title":"COVID-19 in vaccinated adult patients with hematological malignancies: Preliminary results from EPICOVIDEHA","volume":"139","author":"Pagano","year":"2022","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.07.012","article-title":"Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies","volume":"39","author":"Greenberg","year":"2021","journal-title":"Cancer Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.002","article-title":"Seroconversion rates following COVID-19 vaccination among patients with cancer","volume":"39","author":"Thakkar","year":"2021","journal-title":"Cancer Cell"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000523753","article-title":"Vaccination for SARS-CoV-2 in hematological patients","volume":"145","author":"Riccardi","year":"2022","journal-title":"Acta Haematol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s41408-021-00534-z","article-title":"Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies","volume":"11","author":"Malard","year":"2021","journal-title":"Blood Cancer J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.08.001","article-title":"Humoral and cellular immune responses in SARS-CoV-2 mRNA-vaccinated patients with cancer","volume":"39","author":"Mairhofer","year":"2021","journal-title":"Cancer Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.07.016","article-title":"Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer","volume":"39","author":"Ehmsen","year":"2021","journal-title":"Cancer Cell"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279216","article-title":"Humoral serologic response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD20 antibodies","volume":"107","author":"Gurion","year":"2021","journal-title":"Haematologica"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005094","article-title":"mRNA COVID-19 vaccine in patients with b-cell non Hodgkin lymphoma","volume":"5","author":"Perry","year":"2021","journal-title":"Blood Adv"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011568","article-title":"Efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia","volume":"137","author":"Herishanu","year":"2021","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279196","article-title":"Safety and efficacy of BNT162b2 mRNA Covid19 vaccine in patients with chronic lymphocytic leukemia","volume":"107","author":"Benjamini","year":"2021","journal-title":"Haematologica"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2916","article-title":"COVID-19 vaccination: evaluation of risk for protectionfailure in chronic lymphocytic leukemia patients","volume":"39","author":"Del Poeta","year":"2021","journal-title":"Hematol Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.014","article-title":"T-Cell immune response after mRNA SARs-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies","volume":"196","author":"Marasco","year":"2021","journal-title":"Br J Haematol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.014","article-title":"Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma","volume":"39","author":"Van Oekelen","year":"2021","journal-title":"Cancer Cell"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1133348\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T06:31:40Z","timestamp":1677479500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1133348\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":26,"alternative-id":["10.3389\/fonc.2023.1133348"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1133348","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,27]]},"article-number":"1133348"}}