Vaccines for preventing infections in adults with haematological malignancies

- Background Vaccination aims to prevent infections. People who are immunocompromised, such as those with haematological malignancies, often experience higher immunosuppression, increasing their vulnerability to infections compared to individuals with solid tumours or healthy individuals. Objectives The aim of this review is to summarise and evaluate the benefits and risks of vaccines for preventing infections in adults with haematological malignancies. Search methods We conducted a comprehensive systematic search in CENTRAL, MEDLINE, Embase, LILACS, and Web of Science on 2 December 2024 for randomised controlled trials (RCTs) and for controlled non‐randomised studies of interventions (NRSIs). We also searched ClinicalTrials.gov, WHO (World Health Organization) International Clinical Trials Registry Platform (ICTRP), and the Cochrane COVID‐19 Study Register. Selection criteria We included RCTs and controlled NRSIs evaluating the preventive effect of vaccines on outcomes prioritised by clinical experts, patients, and patient representatives. The prioritised outcomes for adults ( ≥ 18 years) with haematological malignancies (excluding those receiving cellular therapies) were infection incidence, all‐cause mortality, quality of life, adverse events of any grade, serious adverse events, and adverse events of special interest. We looked for studies that evaluated a broad range of vaccine types (e.g. COVID‐19, diphtheria, Haemophilus influenzae type b, hepatitis B, herpes zoster, influenza, Neisseria meningitidis , pertussis, polio, Streptococcus pneumoniae , or tetanus), but we excluded live‐attenuated vaccines. Data collection and analysis We followed current Cochrane methodological standards in the conduct of this review. We assessed the risk of bias using the Cochrane risk of bias 2 tool (RoB 2) for RCTs and Risk Of Bias In Non‐randomised Studies ‐ of Interventions (ROBINS‐I) for controlled NRSIs. Main results We included six studies (four RCTs, two controlled NRSIs) with a total of 25,886 participants. We present the RCT results here and the NRSI findings from NRSIs in the full review. We judged one RCT on herpes zoster to be at low risk of bias overall, and we had 'some concerns' about bias in the other RCT on herpes zoster. We had 'some concerns' about bias in the RCTs on COVID‐19 and influenza vaccines. Herpes zoster vaccines Two RCTs, involving 3067 participants with a range of haematological malignancies, evaluated vaccines for preventing herpes zoster compared to placebo or no vaccine. Vaccines may reduce herpes zoster incidence up to 21 months post‐vaccination, although the 95% CI includes the possibility of no effect (4% versus 6%; RR 0.40, 95% CI 0.07 to 2.23; 2 RCTs, 3067 participants; low‐certainty evidence). Vaccines probably have little to no effect on all‐cause mortality up to 28 days post‐vaccination (2.7% versus 2.6%; RR 1.03, 95% CI 0.65 to 1.64; 2548 participants; moderate‐certainty evidence). Vaccines slightly increase any‐grade adverse events within 30 days (RR 1.12, 95% CI 1.07 to 1.18; 3110 participants; high‐certainty evidence), but probably do not increase serious adverse events within 12 months (23% versus 29%; RR 0.79, 95% CI 0.60 to 1.05; 562 participants; moderate‐certainty evidence) after vaccination. Vaccines increase injection site adverse events substantially (40% versus 13%; RR 3.07, 95% CI 2.62 to 3.59; high‐certainty evidence) and also increase systemic adverse events (10% versus 6%; RR 1.82, 95% CI 1.38 to 2.40; high‐certainty evidence), as measured in 2548 participants within 28 days post‐vaccination. Neither RCT reported quality of life. COVID‐19 vaccines One RCT, involving 95 participants with lymphoma, leukaemia or myeloma, evaluated the BNT162b2 COVID‐19 vaccine compared to placebo or no vaccine. Evidence about the effect of BNT162b2 vaccine on the incidence of COVID‐19 up to six months after the second dose compared to placebo or no vaccine remains very uncertain (2.2% versus 2%; RR 1.11, 95% CI 0.07 to 17.25; 1 RCT, 95 participants; very low certainty evidence). Regarding safety data (mixed population including both solid tumours and haematological malignancies), BNT162b2 vaccine probably increases the number of participants with any grade adverse events (35% versus 17.5%; RR 1.99, 95% CI 1.71 to 2.30; 1 RCT, 2328 participants; moderate‐certainty evidence) and there may be little to no difference concerning the number of participants experiencing serious adverse events (2.4% versus 1.7%; RR 1.43, 95% CI 0.80 to 2.54; 1 RCT, 2328 participants; low‐certainty evidence). The RCT did not report all‐cause mortality, quality of life, injection site adverse events or systemic adverse events. Influenza vaccines No RCTs evaluated an influenza vaccine versus placebo or no vaccine. One RCT, involving 122 participants with plasma cell disorders, evaluated different dosing regimens for an influenza vaccine on the incidence of influenza infection. Evidence is very uncertain regarding the effect of two doses of high‐dose trivalent inactivated influenza vaccine compared to one dose (with strength based on age) of influenza vaccination on the incidence of infection within the 2015 to 2016 flu season (4% versus 8%; RR 0.49, 95% CI 0.11 to 2.08; very low‐certainty evidence). The RCT did not report all‐cause mortality, quality of life, any‐grade or serious adverse events, or injection site or systemic adverse events. Authors' conclusions The evidence on vaccines for preventing infections in adults with haematological malignancies is limited and uncertain. Herpes zoster vaccines may reduce infection risk for up to 21 months, but the certainty of the evidence is low. While there is a considerable increase in short‐term adverse events (high‐certainty evidence), no increase in serious adverse events was observed at up to 12 months (moderate‐certainty evidence). Data on long‐term impacts on other outcomes are lacking. For COVID‐19 and influenza vaccines, the evidence is very uncertain. We found no studies that could be included in the review of vaccines for our other infectious diseases of interest: diphtheria, Haemophilus influenzae type b (Hib), hepatitis B, Neisseria meningitidis , pertussis, polio, Streptococcus pneumoniae , or tetanus. Our review underscores the need for high‐quality RCTs and controlled NRSIs with better reporting, larger samples, longer follow‐ups, and a focus on patient‐relevant outcomes, such as quality of life and long‐term safety. A robust and continuously updated evidence base is essential to guide clinical and public health decisions. Plain language summary What are the benefits and risks of vaccines for preventing infectious diseases in adults with blood cancers? Key messages • We found limited evidence on the preventive effect of vaccines on patient‐relevant outcomes in adults with blood cancers. The included studies focused only on herpes zoster, COVID‐19, and influenza vaccines. No studies measured quality of life. • When compared to placebo, herpes zoster vaccines may lower the incidence of infection. They probably result in little to no difference in death from any cause. They cause short‐term side effects, but we did not find an increase in serious side effects up to 12 months post‐vaccination. Long‐term effects on other outcomes are unclear. • For COVID‐19 and influenza vaccines, the evidence measuring the incidence of infection is very uncertain. Side effects were poorly reported or not analysed for people with blood cancers. • Future studies should evaluate vaccines for a wider range of infections and focus on outcomes that matter to patients, such as quality of life and long‐term safety. What is the role of vaccines in people with blood cancers? Vaccines protect people from getting infections by training the immune system to recognise and fight harmful germs. They can also lower the chance of severe illness, hospital stays, and death. For people with blood cancers, vaccines may be especially important because their immune systems are weaker. People with blood cancers often have an increased risk of serious complications from diseases like flu, pneumonia, and COVID‐19. Vaccination, as a preventive measure, aims to reduce the chance of infection, lower the risk of complications, and improve quality of life for people with blood cancers. What did we want to find out? We wanted to understand how vaccines, as a preventive measure, impact important outcomes for adults with blood cancers. Specifically, we wanted to know whether vaccines reduce infections and reduce deaths from any cause. We were also interested in whether vaccines improve quality of life and if they cause any side effects. These include serious side effects such as hospitalisation, and side effects such as pain or redness at the injection site, and systemic (whole‐body) reactions like fever, fatigue, or rash. What did we do? We searched for studies that evaluated vaccines compared to placebo (an inactive intervention that mimics the experimental intervention) or no vaccine. We also looked for studies that compared different vaccine types or doses. We considered a wide range of infectious diseases: COVID‐19, diphtheria, Haemophilus influenzae type b (Hib infection), hepatitis B, herpes zoster, influenza, Neisseria meningitidis (meningitis), pertussis (whooping cough), polio, Streptococcus pneumoniae (pneumonia), and tetanus. We summarised the findings from the studies and assessed our confidence in the evidence, taking into account factors like study design, methods, and sample sizes. What did we find? We found six studies that involved 25,886 adults with various blood cancers and that evaluated vaccines for preventing infections with herpes zoster, COVID‐19, or influenza. No quality of life data were reported in the studies. Most studies were funded by pharmaceutical companies or research institutions and were conducted across multiple countries. We did not find any studies that we could include in the review of vaccines for our other infectious diseases of interest. Main results Four of the six studies we found were 'randomised controlled trials', which is the best study design to answer the questions we were asking. The results reported below are from these four studies. Herpes zoster vaccines For adults with blood cancers, herpes zoster vaccines: • may decrease the risk of herpes zoster infection up to 21 months after vaccination (2 studies, 3067 people); • probably result in no difference in death from any cause (1 study, 2548 people); • slightly increase any side effects within 30 days after vaccination (2 studies, 3110 people); • probably do not increase serious side effects within 12 months after vaccination (1 study, 562 people); and • increase reactions around the injection site and systemic reactions within 28 days after vaccination (1 study, 2548 people). COVID‐19 vaccines For adults with blood cancers: • the evidence on the effect of the BNT162b2 vaccine on the risk of COVID‐19 infection is very uncertain (1 study, 95 people); and • the BNT162b2 vaccine probably increases side effects, though it may make little to no difference to serious side effects six months after the second dose (1 study, 2328 people in a mixed population, i.e. that included both solid and blood cancers). Influenza vaccines For adults with blood cancers: • no studies evaluated an influenza vaccine versus placebo or no vaccine; and • the evidence on the effect of two doses of influenza vaccine ('high‐dose trivalent inactivated') compared to one dose of influenza vaccine (strength dependent on age) is very uncertain (1 study, 122 people). What are the limitations of the evidence? Our confidence in the results is limited. The studies did not address all the infectious diseases or outcomes we were interested in, and there were problems with the study methods, particularly the reporting of results. How up to date is this evidence? The evidence is based on searches run until December 2024.