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.