Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID‐19 vaccine in haemato‐oncological patients with no antibody response

Abstract

Summary Patients with haemato‐oncological malignancies are one of the high‐risk groups for a severe course in case of COVID‐19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato‐oncological patients without antibody response after double‐dose BNT162b2 messenger (m‐)RNA COVID‐19 vaccine. A total of 32 haemato‐oncological non‐responders to double‐dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double‐dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato‐oncological patients.

Fighting Fire with Fire: Immunogenicity of Viral Vectored Vaccines against COVID-19

“…Similar findings were reported for ChAdOx1 nCoV-19 and BNT162b2 [116,117]. In addition, Ad26.COV2.S was shown to be immunogenic in individuals who were immune compromised or did not respond well to mRNA vaccines [118,119]. In all, boosting with VVVs represents a promising approach to enhance immunogenicity, particularly when applied in a heterologous prime-boost regimen.…”

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

“…Patients with haematological malignancies have a higher risk of not seroconverting following vaccination against COVID-19. This effect is most pronounced in patients with B cell malignancies receiving B cell-depleting therapies (CD20 targeted therapies or BTK inhibitors) [144][145][146] . Neutralizing antibody responses, which have been investigated only in limited numbers of patients with cancer, can also be boosted using the same vaccine that was initially administered, even in patients lacking a detectable response after the second dose 101,147 .…”

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

“…The benefit of a third vaccine dose has been investigated in haematology patients, mainly in CLL patients, although on limited numbers and with various times between the 2nd and the 3rd dose. In patients who did not respond to the initial regimen, the seroconversion rates after the 3rd dose was noted between 23–55% [ 66 , 68 , 78 , 79 ]. These rates seem comparable after a homologous [ 66 , 68 , 79 ] or a heterologous [ 78 ] booster.…”

“…In patients who did not respond to the initial regimen, the seroconversion rates after the 3rd dose was noted between 23–55% [ 66 , 68 , 78 , 79 ]. These rates seem comparable after a homologous [ 66 , 68 , 79 ] or a heterologous [ 78 ] booster. Similar to the poor responses to the initial regimen, the on-therapy patients also had the poorest response to booster dose.…”